Why does the same virus cause one symptom in one person and another in a different one?

Tags

Gastrointestinal (GI) tract, Symptom

Question details: For example, for a GI bug, some of my kids will have vomiting, others will have diarrhea, or one unfortunate one will end up with both.

Differences in either genetics and/or exposure (dose) might lead siblings to have different symptoms to the same illness and the two reasons aren’t mutually exclusive.

No two individuals have the exact same biomedical profile, not even identical (monozygotic) twins*.

• The process of Genetic recombination – Wikipedia during Meiosis – Wikipedia in germ cells (ova, sperm) ensures children are born with combinations of traits different not only from their parents but also from each other.
• At greater granularity individuals also differ in Single-nucleotide polymorphism – Wikipedia (SNPs), i.e., differences in single letters of the genetic code.
• Epigenetics – Wikipedia helps further differentiate individuals in the course of their life since each sibling’s interaction with their environment is more or less unique and it leaves singular imprints on their genome even though they are genetically related.
• The process of Somatic recombination – Wikipedia creates a unique Adaptive immune system – Wikipedia in each individual and some or much of this may even have to do with the unique Microbiota – Wikipedia each individual harbors though this is pure speculation at present since we’re currently far from knowing much about this.

These differences form the essential basis for differences in symptoms and severity for the same illness among individuals. However, apart from genetic and immunity differences between hosts, differences in severity of exposure could also explain why this happens, with the sibling with greatest exposure, i.e., dose, more likely to suffer the most severe symptoms. The same sibling repeatedly suffering more severe outcomes for shared illnesses would suggest greater likelihood of underlying genetic difference(s) being at play.

To successfully infect means to first successfully enter a cell, replicate inside it and finally spread to neighboring cells and beyond. Each disease-causing microbe thus evolves to express molecules that mimic those that bind certain cell-surface receptors and this process then serves as its entryway into a particular cell. This preference of a particular microbe to infect certain tissues is its Tissue tropism – Wikipedia. For e.g., the cold virus, Rhinovirus – Wikipedia, and Influenza – Wikipedia primarily target the epithelial cells of the upper respiratory tract, Viral hepatitis – Wikipedia the liver, etc.

Though cells obviously differ in the panoply of what they express on their surface, there’s also considerable overlap between different tissues and these overlaps differ between individuals, both in strength and variety. Thus, given the processes of genetic and somatic recombination, and epigenetics, even related individuals differ in their relative susceptibility to various disease-causing microbes.

This is why some people might get Zika fever – Wikipedia and never know since their symptoms stayed so mild while others may get fever (systemic involvement), joint pain (musculoskeletal) and rashes on their torso (skin) while still others could develop debilitating muscle weakness and pain, Guillain–Barré syndrome – Wikipedia, symptoms that could even be life-threatening.

With a GI tract illness, only vomiting suggests a stringently self-limiting infection that stayed restricted to the upper GI tract, diarrhea suggests a spread into the lower GI tract while both vomiting and diarrhea suggest the most severe outcome, i.e., persistent infection effects in both upper and lower GI tract. Again, simple dose differences in initial exposure could be a trivial explanation for a one-off outcome difference of this kind.

* Tim D. Spector’s long-term studies on identical and fraternal twins show that ‘twins rarely die of the same disease‘ (Why do identical twins end up having such different lives?).

https://www.quora.com/Why-does-the-same-virus-cause-one-symptom-in-one-person-and-another-in-a-different-one/answer/Tirumalai-Kamala

What are some ways to test if you have good gut bacteria?

What constitutes good gut bacteria? What’s their benchmark? We have no clue. Economics of gene sequencing technology means fecal microbiome sequencing costs (1) a fraction of what it did just a few years back. Predictably, companies offering to sequence them have mushroomed, for a price of course. Anyone with a handful of disposable US dollars can get their poop bacteria sequenced but what do those results even mean?

• Should poop contain ~55% Firmicutes, apparently the same as Michael Pollan or 74%, same as the author of this Newsweek piece (2)?
• What’s the value of a one-time poop bacteria sequencing? Isn’t that just a snapshot?
• Studies show poop bacterial composition changes rapidly not just with diet (3) but also seasonally (4) so what’s the predictive value of such a snapshot anyway?
• What does poop bacteria even represent?
  • Isn’t poop bacteria sequenced so much just because it’s easier to access?
  • Doesn’t it really only represent distal colon bacteria supported by current diet?
  • What about what’s in the stomach, duodenum, jejunum, ileum, and proximal and transverse colon, and how they relate to gut and overall health? Don’t we need invasive biopsies to accurately access bacteria in other GI tract compartments?
  • What can we extrapolate from what’s in poop to what should be in other parts of the GI tract? Anything? Nothing?

All this to say a lot of data on poop microbiome’s being generated simply because it can be, not because anyone has a clue what any of it means nor a clue what constitutes good gut bacteria.

To top this litany of shortcomings and dubious value of current attempts to benchmark gut bacteria using fecal microbiome sequencing, at least one randomized placebo-controlled study (5, 6) not only reveals novel, incalculable curative powers of Placebo but also casts doubt on currently accepted notions of ‘good’ and ‘bad’ gut bacteria.

• A study across two US academic medical centers, Montefiore Medical Center in the Bronx, New York and the Miriam Hospital, Providence, Rhode Island, both well-known for their expertise in Fecal microbiota transplant (FMT) (5, 6).
• 46 patients with recurrent Clostridium difficile infection (CDI) were randomly assigned to receive either donor or autologous (their own) poop microbiota, i.e., Placebo.
• 91% (20/22) of those who got donor poop were durably cured based on a standard definition. Expected so no surprise.
• The absolute shocker? 63% (15/24) who got their own poop microbiota transplanted back also had durable cure. Rub eyes and read again. What? Patients with a serious GI tract infection were given back their own presumably disease-associated gut bacteria and they got cured?
• Though there were striking inter-center differences in this Placebo effect, 9/10 (90%) placebo cases in the New York center cured versus only 6/14 (~43%) in the Rhode Island center, and perhaps associated patient population differences between these two centers, those aren’t germane to the central issue, namely, a GI tract disease cured from simply taking out and putting fecal bacteria back into C.diff patients.

Thus, even so-called ‘bad’ gut bacteria turn out to be not so cut and dry, a result that only underlines how little we currently know about gut bacteria, good, bad or anything in between. Best one could then say is absence of persistent and serious health problems, especially gastrointestinal, is evidence of having good gut bacteria. Absence of skin problems, no autoimmunities or mental health issues would be icing on the cake.

Bibliography

1. 16S rRNA sequencing

2. Newsweek, Roxane Khamsi, July 17, 2014. Gut Check

3. David, Lawrence A., et al. “Diet rapidly and reproducibly alters the human gut microbiome.” Nature 505.7484 (2014): 559-563. Diet rapidly and reproducibly alters the human gut
microbiome

4. Davenport, Emily R., et al. “Seasonal variation in human gut microbiome composition.” PloS one 9.3 (2014): e90731. http://www.plosone.org/article/f…

5. Kelly, Colleen R., et al. “Effect of Fecal Microbiota Transplantation on Recurrence in Multiply Recurrent Clostridium difficile Infection: A Randomized Trial.” Annals of Internal Medicine (2016).

6. Fecal Transplant for Relapsing C. Difficile Infection

https://www.quora.com/What-are-some-ways-to-test-if-you-have-good-gut-bacteria/answer/Tirumalai-Kamala

What is the function of bacteria in the human mouth?

Tags

Colonisation resistance, Dental caries, Food web, Gum diseases, oral cavity, Periodontal pathology, tooth decay

Most of the data available so far identifies bacterial species that tend to be associated with healthy versus diseased oral cavities but not much is known about exactly what health-associated ones do apart from keeping out the disease-associated ones.

Oral Cavity, A Complex Ecosystem Of Several Specialized Ecological Niches

Gaining insight begins with the appreciation that the oral cavity is a complex habitat further sub-divided into distinct smaller ones ranging from the non-keratinized Oral mucosa to the keratinized Tongue and gingiva, i.e., Gums, as well as Tooth enamel and a variety of dental implants. Thus, depending on its proximity to the gum line, dental plaque is either supra- or subgingival, and the bacteria that inhabit these two regions are different, supragingival plaque dominated by gram-positive Streptococci while subgingival by gram-negative anaerobic bacteria (1).

Since the oral cavity is exposed to the outside world, these surfaces are colonized soon after birth, with some evidence suggesting vertical (mother-to-baby) transmission (2) as well as similarities between family members (3). Stable inhabitants, formally called autochthonous, establish Biofilm, a kind of super-organism consisting of cooperating microbes. Being open, oral cavity also gets plenty of visitors, transients, formally called allochthonous.

Older studies suggested oral cavity diseases are associated with changes in microbial diversity (1).

Gum diseases, i.e., Periodontal pathology, and tooth decay, i.e., Dental caries, are associated with increase (4, 5, 6) and decrease (7), respectively, in microbial diversity. More recent state-of-the-art molecular approaches (8, 9) confirm these decades-old findings. This implies oral cavity disease isn’t so much a matter of presence or absence of certain microbes since those with disease-causing potential, i.e., pathobionts, are present even in health (10) but rather about their relative proportions in complex biofilms.

Colonisation resistance Is A Key Feature Of Healthy Oral Cavity Microbiota

Like other microbe-associated body sites, the oral cavity too is a series of specialized niches occupied by specific microbes capable of specialized functions both necessary and predicated on some inherent properties of these niches. The ones who establish stable presence in the form of complex, multi-species biofilms dominate their specific niches by preventing others, including pathogens, from establishing themselves, i.e., Colonization Resistance (11). When the oral cavity is stably colonized by beneficial microbe biofilms, it’s healthy. Instability in beneficial microbe colonization is a weakness that’s then exploited by more harmful and even pathogenic species to dominate oral cavity biofilms, with the outcome either tooth decay (Dental Caries) or gum disease (Periodontitis).

Tooth decay (Dental caries) is associated with certain species of Streptococci such as Streptococcus mutans and species of Lactobacilli (12) while subgingival anaerobes establish their communities within periodontal pockets, some of whom such as Porphyromonas gingivalis are associated with gum disease (Periodontitis) (13, 14).

Obviously diet profoundly influences not only which bacterial species stably establish within oral biofilms but also dominate.

• Thus though S. mutans is part of normal oral microbiota (15), it doesn’t dominate in healthy oral cavities.
• However, its capacity to metabolize sucrose more efficiently compared to other oral bacteria (16) gives it a competitive advantage in the oral cavities of those who predominantly consume the highly processed, sucrose-heavy ‘Western’ diet.
• S. mutans can also convert sucrose to adherent glucans, which helps it to attach more strongly to teeth (17).
• S. mutans also rapidly converts sucrose to lactic acid, giving it an added selective advantage owing to its intrinsic capacity to withstand such acidic environments (18, 19).
• These properties may help S. mutans and Lactobacilli dominate in tooth decay, i.e., dental caries, the latter because they metabolize lactic acid generated by S.mutans.

Similar studies done decades apart, scraping plaques from people with or without gum disease and culturing the bacteria that grew out with bacterial species associated with gum disease showed plaques from people without gum disease can inhibit growth of gum disease-associated bacterial species (20, 21). How?

• Streptococcus sanguinis is considered an inhabitant of normal dental plaque. Less acid-tolerant than its presumed niche competitor, S. mutans, S. sanguinis produces Hydrogen peroxide, toxic for S. mutans, which typically lacks capacity to effectively neutralize it (22, 23). Thus, dental plaques rich in S. sanguinis contain relatively lower proportions of dental caries-associated S. mutans and periodontitis-associated P. gingivalis (20).
• Veillonella species (24) and S. oligofermentans (25) readily metabolize lactic acid secreted by S. mutans. A revealing window into how inter-species competition can engender colonization resistance, S. oligofermentans not only utilizes S. mutans-generated lactic acid but converts it into hydrogen peroxide, highly toxic to the latter (26).
• Streptococcus gordonii offers another plausible example of colonization resistance tactic. Another inhabitant of healthy oral cavities, in vitro it could prevent stable S. mutans colonization by inactivating one of its important resistance mechanisms , ability to synthesize a Quorum sensing molecule, CSP (competence-stimulating peptide) (27). When thus hobbled, S. mutans is much less capable of resisting natural salivary antimicrobial peptides such as Histatin (1).
• Oral cavity bacteria also secrete Bacteriocin. Proteinaceous toxins, bacteriocins differ from antibiotics, having a much narrower killing spectrum and acting on related organisms (1).

Thus, as long as diet is varied enough to also allow stable plaque colonization by base-producing microbes, acid-producing S. mutans wouldn’t be able to predominate and take over local plaque ecosystem.

Food web Relationships Between Normal Oral Cavity Microbes Help Maintain Their Stability

As is the hallmark of ecosystems consisting of mutually dependent residents, the healthy oral cavity too contains microbes engaged in Food web activities, i.e., metabolic end products of one species used by others.

• Oral biofilm Streptococci synthesize lactate that Veillonella use (1).
• S. sanguis and S. oralis are inhabitants of healthy oral biofilms. In vitro culture studies suggest their mutually helpful, i.e., synergistic, capacity to digest mucins helps them more efficiently use such complex host sugars as nutrition (28).
• Oral cavity is constantly bathed in saliva and gingival crevicular fluid. Composite of products of not just human tissue cells but also microbes, some microbial inhabitants appear to engage in synergistic/mutualistic interactions to overcome inherent handicaps to colonize. This seems to be the case with Actinomyces naeslundii and S. oralis that alone colonize saliva-coated surfaces poorly and yet can form extensive biofilms together by presumably combining their metabolic activities (29).

However, food web processes can also help shift oral biofilms to dominance by more pathogenic species. Though inhabitants of normal oral cavity, P. gingivalis, Fusobacterium nucleatum, Treponema denticola and Tannerella forsythia are also implicated in periodontal disease.

• In vitro culture studies show P. gingivalis can metabolize succinate produced by T. denticola (30) while the latter can use isobutyric acid secreted by the former (31).
• Both F. nucleatum and T. forsythia seem to secrete factors that stimulate growth of P. gingivalis (1).

Thus, whether mutualistic interactions of beneficial or harmful bacteria dominate in a given oral cavity is outcome of diet, oral hygiene and host genetic polymorphisms.

Why Knowledge Of Bacteria Function In Healthy Oral Cavity Is Better Gleaned From Older, Not Newer, Studies

Since the 2000s an explosion in molecular biological tools, so-called Omics, has led to a similar explosion in human microbiome studies. Since the oral cavity is one of the most easily accessible of all the GI tract niches, human oral cavity microbiome has become the best characterized in terms of the kinds of bacteria present in healthy versus unhealthy mouths.

• Since such typically technocratically driven processes focus primarily on generating an avalanche of data and explore no underlying hypotheses, one may wonder whether the healthy human oral cavity microbiome’s function is simply absence of disease. That is to say, given the monumental scale of molecular biology data generated on this topic since at least the mid-2000s, it’s shocking how little is known about what any of it even means.
• With older prejudices implicitly carried forward, there’s also been no attempt so far to synthesize the roles of bacteria and fungi in healthy oral cavities since fungi like Candida albicans were previously assumed to only represent disease states. Their repeated presence in healthy oral cavities suggests this idea needs revising (32).
• Even less is known about role of Archaea such as Methanobrevibacter species frequently found in healthy oral cavities. Their increasing identification in gum disease (Periodontal pathology) suggests they too may be involved in such disease processes but how? Only in promoting growth of pathogenic bacterial species (33) or as initiators and perpetuators themselves?
• Meantime overweening allegiance to novel technologies is powering this entire absurd process forward with the implicit hope that Data mining will uncover hidden patterns allowing certain predictive hypotheses to be made.
• If past is any predictor of future, the failure of past dependence on novel molecular biological approaches alone to yield predictive insight into complex biological phenomena suggests a similar fate awaits the current giddy immersion in the latest molecular biological toys. A useful and telling example from the recent past is Microarray analysis techniques, the focus of tens of thousands of papers since the late 1990s, which nevertheless yielded little or no improved insight into disease processes nor did they much illuminate possible future predictive approaches to better understand them.
• Necessity of extrapolating data from in vitro culture studies referenced in this answer is their major caveat. Nevertheless, we’d understand oral cavity-bacteria interactions better with more such experiments, especially in vitro co-cultures of human oral epithelial cells with candidate oral cavity commensals, more so co-cultures with commensal biofilms but such experimental approaches are technically much more challenging compared to powering a few cheek swab or saliva samples through the latest molecular biology apparatus. Hence the current absurd status quo.

Bibliography

1. Kuramitsu, Howard K., et al. “Interspecies interactions within oral microbial communities.” Microbiology and molecular biology reviews 71.4 (2007): 653-670. Interspecies Interactions within Oral Microbial Communities

2. Kobayashi, N., et al. “Colonization pattern of periodontal bacteria in Japanese children and their mothers.” Journal of periodontal research 43.2 (2008): 156-161. https://www.researchgate.net/pro…

3. Steenbergen, TJM van, et al. “Intra‐familial transmission and distribution of Prevotella intermedia and Prevotella nigrescens.” Journal of periodontal research 32.4 (1997): 345-350.

4. Löe, Harald, Else Theilade, and S. Börglum Jensen. “Experimental gingivitis in man.” Journal of periodontology 36.3 (1965): 177-187.

5. Listgarten, M. A. “Structure of the Microbial Flora Associated with Periodontal Health and Disease in Man: A Light and Electron Microscopic Study*.” Journal of periodontology 47.1 (1976): 1-18.

6. Syed, S. A., and W. J. Loesche. “Bacteriology of human experimental gingivitis: effect of plaque age.” Infection and immunity 21.3 (1978): 821-829.

7. Simon-Soro, A., et al. “A tissue-dependent hypothesis of dental caries.” Caries research 47.6 (2013): 591-600.

8. Diaz, P. I., A. Hoare, and B. Y. Hong. “Subgingival Microbiome Shifts and Community Dynamics in Periodontal Diseases.” Journal of the California Dental Association 44.7 (2016): 421. http://www.cda.org/Portals/0/jou…

9. Tanner, A. C., C. A. Kressirer, and L. L. Faller. “Understanding Caries From the Oral Microbiome Perspective.” Journal of the California Dental Association 44.7 (2016): 437. http://www.cda.org/Portals/0/jou…

10. Jiao, Y., M. Hasegawa, and N. Inohara. “The role of oral pathobionts in dysbiosis during periodontitis development.” Journal of dental research 93.6 (2014): 539-546. https://www.researchgate.net/pro…

11. Van der Waaij, D., J. M. Berghuis-de Vries, and J. E. C. Lekkerkerk-Van der Wees. “Colonization resistance of the digestive tract in conventional and antibiotic-treated mice.” Journal of Hygiene 69.03 (1971): 405-411. https://www.researchgate.net/pro…

12. Chhour, Kim-Ly, et al. “Molecular analysis of microbial diversity in advanced caries.” Journal of clinical microbiology 43.2 (2005): 843-849. Molecular Analysis of Microbial Diversity in Advanced Caries

13. ÖSterberg, Stic K‐Å., Sara Z. Sudo, and Lars EA Folke. “Microbial succession in subgingival plaque of man.” Journal of periodontal research 11.5 (1976): 243-255.

14. Ximénez‐Fyvie, Laurie Ann, Anne D. Haffajee, and Sigmund S. Socransky. “Microbial composition of supra‐and subgingival plaque in subjects with adult periodontitis.” Journal of clinical periodontology 27.10 (2000): 722-732. https://www.researchgate.net/pro…

15. Aas, Jørn A., et al. “Defining the normal bacterial flora of the oral cavity.” Journal of clinical microbiology 43.11 (2005): 5721-5732. Defining the Normal Bacterial Flora of the Oral Cavity

16. Hamada, Shigeyuki, and HUTTON D. Slade. “Biology, immunology, and cariogenicity of Streptococcus mutans.” Microbiological reviews 44.2 (1980): 331. http://www.ncbi.nlm.nih.gov/pmc/…

17. Gibbons, R. J., and M. Nygaard. “Synthesis of insoluble dextran and its significance in the formation of gelatinous deposits by plaque-forming streptococci.” Archives of oral biology 13.10 (1968): 1249-IN31.

18. Grenier, Daniel. “Antagonistic effect of oral bacteria towards Treponema denticola.” Journal of clinical microbiology 34.5 (1996): 1249-1252. Antagonistic effect of oral bacteria towards Treponema denticola.

19. Doran, A., S. Kneist, and Joanna Verran. “Ecological control: in vitro inhibition of anaerobic bacteria by oral streptococci.” Microbial Ecology in Health and Disease 16.1 (2004): 23-27. https://www.researchgate.net/pro…

20. Hillman, J. D., S. S. Socransky, and Myra Shivers. “The relationships between streptococcal species and periodontopathic bacteria in human dental plaque.” Archives of Oral Biology 30.11-12 (1985): 791-795.

21. van Essche, Mark, et al. “Bacterial antagonism against periodontopathogens.” Journal of periodontology 84.6 (2013): 801-811.

22. Carlsson, Jan, and May‐Britt K. Edlund. “Pyruvate oxidase in Streptococcus sanguis under various growth conditions.” Oral microbiology and immunology 2.1 (1987): 10-14.

23. Kreth, Jens, et al. “Competition and coexistence between Streptococcus mutans and Streptococcus sanguinis in the dental biofilm.” Journal of bacteriology 187.21 (2005): 7193-7203. Competition and Coexistence between Streptococcus mutans and Streptococcus sanguinis in the Dental Biofilm

24. Mikx, F. H. M., and J. S. Van der Hoeven. “Symbiosis of Streptococcus mutans and Veillonella alcalescens in mixed continuous cultures.” Archives of Oral Biology 20.7 (1975): 407-410.

25. Tong, Huichun, et al. “Streptococcus oligofermentans inhibits Streptococcus mutans through conversion of lactic acid into inhibitory H2O2: a possible counteroffensive strategy for interspecies competition.” Molecular microbiology 63.3 (2007): 872-880. https://www.researchgate.net/pro…

26. Bao, Xudong, et al. “Streptococcus oligofermentans inhibits Streptococcus mutans in biofilms at both neutral pH and cariogenic conditions.” PloS one 10.6 (2015): e0130962. http://journals.plos.org/plosone…

27. Wang, Bing-Yan, and Howard K. Kuramitsu. “Interactions between oral bacteria: inhibition of Streptococcus mutans bacteriocin production by Streptococcus gordonii.” Applied and environmental microbiology 71.1 (2005): 354-362. Inhibition of Streptococcus mutans Bacteriocin Production by Streptococcus gordonii.

28. Van der Hoeven, J. S., and P. J. M. Camp. “Synergistic degradation of mucin by Streptococcus oralis and Streptococcus sanguis in mixed chemostat cultures.” Journal of dental research 70.7 (1991): 1041-1044. http://citeseerx.ist.psu.edu/vie…

29. Palmer, Robert J., et al. “Mutualism versus independence: strategies of mixed-species oral biofilms in vitro using saliva as the sole nutrient source.” Infection and immunity 69.9 (2001): 5794-5804. Strategies of Mixed-Species Oral Biofilms In Vitro Using Saliva as the Sole Nutrient Source

30. Grenier, D., and D. Mayrand. “Nutritional relationships between oral bacteria.” Infection and immunity 53.3 (1986): 616-620. Nutritional relationships between oral bacteria.

31. Grenier, D. “Nutritional interactions between two suspected periodontopathogens, Treponema denticola and Porphyromonas gingivalis.” Infection and immunity 60.12 (1992): 5298-5301. Nutritional interactions between two suspected periodontopathogens, Treponema denticola and Porphyromonas gingivalis.

32. Krom, B. P., S. Kidwai, and J. M. Ten Cate. “Candida and Other Fungal Species Forgotten Players of Healthy Oral Microbiota.” Journal of dental research 93.5 (2014): 445-451. https://www.researchgate.net/pro…

33. Bang, Corinna, and Ruth A. Schmitz. “Archaea associated with human surfaces: not to be underestimated.” FEMS microbiology reviews (2015): fuv010. http://femsre.oxfordjournals.org…

https://www.quora.com/What-is-the-function-of-bacteria-in-the-human-mouth/answer/Tirumalai-Kamala

Microbiology: What different kinds of symbioses do humans have with bacteria?

Tags

colonic butyrate, Faecalibacterium (formerly Fusobacterium) prausnitzii

Since human microbiota study’s still in its infancy, strong, conclusive proof of symbiotic associations aren’t yet available. Rather, strong correlations are. Proof of symbiosis requires

1. A specific bacterial species consistently associated with several humans across time.
2. Abundance in health versus reduction in disease.
3. Successful re-planting of such a species into a diseased body should fully or partially restore health.

Further, being genetically diverse, geographically widespread, and having extremely varied diets, human-microbe symbioses are probably redundant between bacterial species and even across genera. This makes the 3rd proposition difficult to prove. Decisive proof becomes even more difficult given bacterial species associated with humans are being identified at exponential pace. For e.g., in the GI tract alone, bacterial species identified have increased from ~300 in 1980 to ~1000 by 2010 due to molecular technologies  (see figure below from 1).

Substantial data supports at least the first two conditions in the example of Faecalibacterium (formerly Fusobacterium) prausnitzii, associated with the colon.

• Presence confirmed by both culture (2) and 16SrRNA (3, 4, 5, 6), F. prausnitzii is one of the most abundant anaerobic bacteria in human colon and feces.
• Possible symbiotic function? One of the main sources of colonic butyrate (3, 7), generally considered beneficial to intestinal health as well as a preferred energy source for colonic epithelial cells, the colonocytes (8, 9, 10).
• Reduced presence in a variety of inflammatory bowel diseases (11, 12, 13, 14) including Crohn’s disease (15, 16, 17) and colorectal cancer (18, 19).

Bibliography

1. Rajilić-Stojanović, Mirjana, and Willem M. de Vos. “The first 1000 cultured species of the human gastrointestinal microbiota.” FEMS microbiology reviews 38.5 (2014): 996-1047. http://femsre.oxfordjournals.org…

2. Moore, W. E., and Lillian H. Moore. “Intestinal floras of populations that have a high risk of colon cancer.” Applied and environmental microbiology 61.9 (1995): 3202-3207. Intestinal floras of populations that have a high risk of colon cancer.

3. Hold, Georgina L., et al. “Oligonucleotide probes that detect quantitatively significant groups of butyrate-producing bacteria in human feces.” Applied and environmental microbiology 69.7 (2003): 4320-4324. Oligonucleotide Probes That Detect Quantitatively Significant Groups of Butyrate-Producing Bacteria in Human Feces

4. Suau, Antonia, et al. “Direct analysis of genes encoding 16S rRNA from complex communities reveals many novel molecular species within the human gut.” Applied and environmental microbiology 65.11 (1999): 4799-4807. Direct Analysis of Genes Encoding 16S rRNA from Complex Communities Reveals Many Novel Molecular Species within the Human Gut

5. Suau, Antonia, et al. “Fusobacterium prausnitzii and related species represent a dominant group within the human fecal flora.” Systematic and Applied Microbiology 24.1 (2001): 139-145. https://www.researchgate.net/pro…

6. Walker, Alan W., et al. “Dominant and diet-responsive groups of bacteria within the human colonic microbiota.” The ISME journal 5.2 (2011): 220-230. http://www.nature.com/ismej/jour…

7. Barcenilla, Adela, et al. “Phylogenetic relationships of butyrate-producing bacteria from the human gut.” Applied and environmental microbiology 66.4 (2000): 1654-1661. Phylogenetic Relationships of Butyrate-Producing Bacteria from the Human Gut

8. Hamer, Henrike M., et al. “Review article: the role of butyrate on colonic function.” Alimentary pharmacology & therapeutics 27.2 (2008): 104-119. http://onlinelibrary.wiley.com/d…

9. Pryde, Susan E., et al. “The microbiology of butyrate formation in the human colon.” FEMS microbiology letters 217.2 (2002): 133-139. http://femsle.oxfordjournals.org…

10. Roediger, W. E. W. “The colonic epithelium in ulcerative colitis: an energy-deficiency disease?.” The Lancet 316.8197 (1980): 712-715.

11. Sartor, R. Balfour. “Therapeutic correction of bacterial dysbiosis discovered by molecular techniques.” Proceedings of the National Academy of Sciences 105.43 (2008): 16413-16414. http://www.pnas.org/content/105/…

12. Cucchiara, Salvatore, et al. “The microbiota in inflammatory bowel disease in different age groups.” Digestive Diseases 27.3 (2009): 252-258.

13. Sokol, H., et al. “Low counts of Faecalibacterium prausnitzii in colitis microbiota.” Inflammatory bowel diseases 15.8 (2009): 1183-1189. https://www.researchgate.net/pro…

14. Schwiertz, Andreas, et al. “Microbiota in pediatric inflammatory bowel disease.” The Journal of pediatrics 157.2 (2010): 240-244. https://www.researchgate.net/pro…

15. Sokol, Harry, et al. “Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients.” Proceedings of the National Academy of Sciences 105.43 (2008): 16731-16736. http://www.pnas.org/content/105/…

16. Willing, Ben, et al. “Twin studies reveal specific imbalances in the mucosa‐associated microbiota of patients with ileal Crohn’s disease.” Inflammatory bowel diseases 15.5 (2009): 653-660. https://www.researchgate.net/pro…

17. Kang, Seungha, et al. “Dysbiosis of fecal microbiota in Crohn’s disease patients as revealed by a custom phylogenetic microarray.” Inflammatory bowel diseases 16.12 (2010): 2034-2042. https://www.researchgate.net/pro…

18. Balamurugan, Ramadass, et al. “Real‐time polymerase chain reaction quantification of specific butyrate‐producing bacteria, Desulfovibrio and Enterococcus faecalis in the feces of patients with colorectal cancer.” Journal of gastroenterology and hepatology 23.8pt1 (2008): 1298-1303. https://www.researchgate.net/pro…

19. Chen, Weiguang, et al. “Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer.” PloS one 7.6 (2012): e39743. http://www.plosone.org/article/f…

https://www.quora.com/Microbiology-What-different-kinds-of-symbioses-do-humans-have-with-bacteria/answer/Tirumalai-Kamala

If we know that overusing antibiotics will cause resistant bacteria, why do we still give out so much of it? Especially in some parts of the world?

Tags

AGP (Antimicrobial Growth Promotion), CAFO (Confined Animal Feeding Operations), IFAP (Industrial Food Animal Production)

Before we can conceive solutions to a problem, we need to accurately identify the source(s) of said problem. Rather than a one-way street where doctors simply unnecessarily prescribe too many antibiotics and the rest of us just haplessly consume them, 3 C’s, namely, culture, convenience, cost explain why we overuse antibiotics even though it’s undeniably counterproductive, for us, for our future and for the future of untold life forms on this planet. No one gets to wag a finger at others on this issue. All of human society is complicit in creating or enabling the culture of antibiotic over-usage.

Our culture actively enables, even encourages, excessive antimicrobial use
First, the cultural norm that ‘germs‘ are bad and need to be eliminated from our bodies, our lives and our environment. Why do ads proudly extol cleaners, wipes, sprays and lotions that eliminate 99.9% of germs? Because we, the consumers of such ads, tacitly agree that ‘germs‘ are bad and need to be eliminated from our lives. The prescribing and consuming of vast amounts of antibiotics occurs not in a vacuum but in thrall to a cultural construct of microbe-as-our-mortal-enemy that’s prevailed since the late 19th century when Koch and Pasteur discovered them in the context of human diseases. An absurdly wrong-headed notion of course but substantial numbers among us continue to believe it, and all because of that historical accident of how microbes were discovered. It’ll take time, maybe even generational time for the concept of human as human-microbe ecosystem to percolate through to society at large. Only then will the cultural norm shift to microbe as not our enemy. The distinction is nuanced but critical. Some, not all, microbes are pathogenic.

Our short-sighted focus on convenience and cost enables, even encourages, excessive antimicrobial use. How? Simple. We insist on abundant and cheap meat consumption.
Second, human antibiotic use is easily dwarfed by the scale of antibiotic use in industrial livestock agriculture.

Until fairly recently in recent human history, meat eating was by and large a luxury, typically consumed infrequently such as once a week, say the traditional Sunday post-church supper in pre-20th century USA. If meat-eaters, especially meat-eaters descended from meat-eaters cared to reminisce on familial practices, they would invariably reach an inflection point in their recent past prior to which meat was a luxury, a relatively rare treat for most humans.

Fast forward to today and in industrialized nations, frequent and copious meat eating is the norm. In fact meat eating is now a luxury for only a relatively tiny, decidedly marginalized and impoverished fraction of the population. In the US, for example, meat and fast food are mostly synonymous, and fast food joints are the mainstay of strip malls permeating the American landscape in superfluous abundance like dandelion seeds in fallow fields. Fast food in turn is economically cheap food, affordable by all but the poorest. Unsustainable at best, the deep-rooted and vexing problem is that it’s also eminently desirable in the popular imagination. Thus, such decidedly odious cultural practices as cheap and copious meat-eating end up becoming the norm. For e.g., recently China has even overtaken the rest in total meat production and consumption rates. Over the century or so as this tidal wave of cultural change set in, meat supplies grew, not modestly, but decidedly exponentially. How could this happen and so rapidly? How did meat become so abundant so suddenly? Widespread refrigeration and refrigerated transport? Certainly helped in making meat widely available but they couldn’t create over-abundant amounts of meat in the first place. Industrialization of livestock or industrial food animal production (IFAP) in CAFO (Confined Animal Feeding Operations) needed something else to spark over-abundant meat yields.

Antimicrobial Growth Promotion (AGP) in Industrial Food Animal Production (IFAP) is far and away the largest use of antibiotics
As food animal production rapidly switched from the pre-industrial pastoral mode to IFAP, especially CAFO, exponentially increased meat yields couldn’t happen without AGP. AGP what? AGP as in Antimicrobial Growth Promotion

• As seems the norm in science, discovered by accident, still not understood, AGP is a poster child of decidedly mindless commercial exploitation.
• World War II was a time of widespread protein shortage, even in the US.
• Soy and corn were the mainstay for livestock. Such diets lacked essential B vitamins.
• Looking for a cheap vitamin B12 source, scientists at Lederle Laboratories found that Streptomyces aureofaciens cultures used for producing chlortetracycline (Aureomycin) were as effective as animal liver extracts in enhancing vitamin B12-deficient chickens (1). Turned out the effect came from the antibiotic.
  • Pure aureomycin, penicillin and streptomycin enhanced chicken and pig growth (1, 2).
  • Turns out sub-therapeutic antibiotic treatments mysteriously accelerated livestock growth.
  • Less feed costs, less time to market. The economic rationale wrote itself.
  • Flurry of patents followed, and AGP became firmly ensconced in the IFAP system.

• AGP in IFAP by far dwarfs human consumption of antibiotics, by at least ~4X conservatively (see figures below from 3).
• China leads world usage of antibiotics by leaps and bounds (see figure below from 3).
• Another mystery? Only anti-bacterials, not anti-fungals or anti-virals, produced this magic rapid weight gain effect.
• Rapid weight gain, not treatment of bacterial illness, drives humungous antibiotic use in farm animals. In other words, impetus for AGP is economic, not medical.

 

• Of course, no surprise that AGP in IFAP inevitably leads to bacterial antibiotic resistance in humans.
• First reported in 1976 (4), steady avalanche of studies shows agricultural antibiotic use contributes to widespread bacterial resistance (see figure from 5 below for a recent example from Spain).
• In fact, in 2002 an entire issue of the scientific journal, Clinical Infectious Diseases, focused on the link between prophylactic antibiotic use in CAFO and generalized antibiotic resistance in bacteria (6).

From antibiotics used in AGP for IFAP is a short step to well their presence everywhere (see figure below from 7).
1. Antibiotic-resistant bacteria colonize and grow

• in animals.
• on surfaces.
• in manure.
• and are carried beyond by flies, rats, wild birds.

2. Airborne pathogens from IFAP are spread by

• Ventilation Fans.
• Decomposing manure.

3. IFAP workers have

• Higher rates of respiratory illness.
• Higher rates of psychological distress.
• Colonized by antibiotic-resistant bacteria.
• Which are potentially transmissible to their communities.

4. IFAP waste is usually spread on agricultural lands

• Includes antibiotics, excreted hormones, heavy metals.
• Spreads into environment through ground and surface waters.

Horizontal gene transfer further spreads antibiotic-resistant genes far beyond IFAP, microbe-to-microbe all through the environment.

 

Meta-analysis of 33 studies on community exposure to IFAP (see figure below from 7) shows that it’s associated with

• Respiratory problems.
• MRSA (Methicillin-resistant Staphylococcus aureus) colonization.
• Q fever.
• Stress.

A 2008 review in the Annual Reviews of Public Health (5) succinctly summarizes the grave risks that ensue from such widespread antibiotic use, risks to not just human health but to all of our ecosystem.

Even more profound than antibiotics permeating all through our environment from massive IFAP use is the potential for their effect on every living cell.

• Our mitochondria originated from bacteria themselves, proteobacteria to be precise, and recent studies show that many clinically approved antibiotics such as tetracyclines can potently inhibit mitochondrial ribosomes and protein synthesis (8).
• Similar effects also seen in plant chloroplasts, another ancient bacterial remnant inside eukaryotic cells (8).
• Thus, antibiotic influence of metabolism and function extends far beyond bacteria.
• It’s one thing to take antibiotics to stave off an infection.
• Quite another to be constantly exposed to them pervasively through our environment.
• But that’s the largely invisible price for our mindless insistence on cheap and abundant meat.

So what can be done to reduce such excessive antibiotic use? What can WHO/UN do? Rather can they do something, anything?

Small countries first, followed by the EU as a whole led the way in banning AGP in IFAP

• Denmark banned AGP, i.e., non-therapeutic antibiotics in farm animals followed by a complete EU ban by 2006.
• Unfortunately, this led to increased therapeutic antibiotic use in livestock. Obviously some other way was needed.
• In the Netherlands, a unique confluence of government policies, public pressure and voluntary private sector participation reduced all antibiotic use in IFAP by >50% in just 5 years (see figures below from 9).
• While this is heartening, there is no simple formula or blueprint to disseminate this practice to other countries.
• Rather, each country will likely evolve its own unique path to AGP-free farming.
• Maybe it will even take an epidemic or two or three.

 

 

These government and public pressure-driven policy changes drive the obvious question.

• If AGP drove accelerated weight gain which in turn engendered lower feed costs and less time to market, how could cheap and abundant meat production be sustained when AGP’s removed?
• Turns out, the mystery of the AGP effect is not so mysterious after all.
• AGP’s rendered superfluous when food animals are housed cleanly with diligent attention paid to their hygiene.
• Analysis of data generated by a commercial chicken supplier itself (a US company called Perdue) showed this to be the case (5, 10, 11, 12).
• So AGP wasn’t driven by just simple economic sense. Sheer sloth plays a role. As well disdain as in disdain for the very life forms being raised in the billions for food.

Bottomline, these data serve to highlight several knotty and distasteful conundrums.

• One, they illuminate the extensive degree to which science remains subservient to culture.
• Two, out of sight, out of mind. Billions of animals forcibly raised in CAFO is the invisible iceberg sustaining current sky-rocketing meat consumption levels. Sustaining? That’s at the very least obscenely funny because there’s nothing sustainable about the IFAP system.
• And certainly nothing healthy about antibiotic use in IFAP. But hey, at least the meat’s cheap and convenient.

With such equations firmly ensconced in our societies, we cannot expect logic and reason to prevail. Even the most persuasive rational arguments are likely to fail because we time and again demonstrate Pavlovian preference for convenience and cost. The Guardian newspaper recently wrote that Industrial farming is one of the worst crimes in history. One of the worst? Hardly does justice. The worst? Certainly. Even more so given the astronomical and utterly atrocious degree of global food wastage. Estimates suggest that a third to a half of all world food production is simply wasted (rots/thrown away) (*).

Major recent government reports that draw a line in the sand, or at least attempt to do so, against the practice of AGP in IFAP include those by the European Food Safety Authority (EFSA), the Union of Concerned Scientists, the US Institute of Medicine published by the National Academies Press, and the US FDA (Food and Drug Administration) and USDA (the US Department of Agriculture).
EFSA reports:
Page on efsa.europa.eu
Page on efsa.europa.eu
Union of Concerned Scientists:
Page on ucsusa.org
US Institute of Medicine (IOM) reports published by the National Academies Press:
Reading: Microbial Threats to Health: Emergence, Detection, and Response
Reading: Antibiotic Resistance: Implications for Global Health and Novel Intervention Strategies: Workshop Summary
FDA’s 2012 Guidance document on use of antibiotics in livestock agriculture:
Page on fda.gov
USDA’s 2009 report:
Page on usda.gov

Bibliography

1. Jukes, T. H. “The history of the” antibiotic growth effect”.” Federation proceedings. Vol. 36. No. 11. 1977.
2. Luecke, R. W., et al. “The growth promoting effects of various antibiotics on pigs.” Journal of animal science 10.2 (1951): 538-542.
3. Wang, Xu, et al. “Antibiotic use and abuse: A threat to mitochondria and chloroplasts with impact on research, health, and environment.” BioEssays 37.10 (2015): 1045-1053. Page on wiley.com
4. Levy, Stuart B., George B. FitzGerald, and Ann B. Macone. “Changes in intestinal flora of farm personnel after introduction of a tetracycline-supplemented feed on a farm.” New England Journal of Medicine 295.11 (1976): 583-588.
5. Silbergeld, Ellen K., Jay Graham, and Lance B. Price. “Industrial food animal production, antimicrobial resistance, and human health.” Annu. Rev. Public Health 29 (2008): 151-169. http://www.researchgate.net/prof…
6. Clinical Infectious Diseases, Volume 34 Supplement 3 June 1, 2002  Table of Contents
7. Casey, Joan A., et al. “Industrial Food Animal Production and Community Health.” Current environmental health reports 2.3 (2015): 259-271. Page on researchgate.net
8. Wang, Xu, et al. “Antibiotic use and abuse: A threat to mitochondria and chloroplasts with impact on research, health, and environment.” BioEssays 37.10 (2015): 1045-1053. Page on wiley.com
9. Speksnijder, D. C., et al. “Reduction of veterinary antimicrobial use in the Netherlands. the Dutch success model.” Zoonoses and public health 62.s1 (2015): 79-87. Page on wiley.com
10. Engster, H. M., D. Marvil, and B. Stewart-Brown. “The effect of withdrawing growth promoting antibiotics from broiler chickens: a long-term commercial industry study.” The Journal of Applied Poultry Research 11.4 (2002): 431-436. Page on oxfordjournals.org
11. Graham, Jay P., John J. Boland, and Ellen Silbergeld. “Growth promoting antibiotics in food animal production: an economic analysis.” Public health reports 122.1 (2007): 79. Page on nih.gov
12. Miller, Gay Y., et al. “Productivity and economic effects of antibiotics used for growth promotion in US pork production.” Journal of agricultural and applied economics 35.03 (2003): 469-482. http://ageconsearch.umn.edu/bits…

* Tirumalai Kamala’s answer to How can a physicist, mathematician, or computational scientist get involved with solving world hunger?

https://www.quora.com/If-we-know-that-overusing-antibiotics-will-cause-resistant-bacteria-why-do-we-still-give-out-so-much-of-it-Especially-in-some-parts-of-the-world/answer/Tirumalai-Kamala

 

What are some human-borne viruses/bacteria that could kill plants by contamination? For instance, if I had someone go in my greenhouse, do they pose any biological risk to the plants? Is there even a remote possibility of a plant getting “sick” from human contact?

Way this question’s phrased makes me interpret it as two questions in one.

• One, humans as transporters of plant disease, on their clothes, shoes, etc.
• Two, common disease agents of humans and plants.
• There is more compelling evidence for the former, less for the latter, with the caveat that there are many more studies exploring the potential of plants and plant products as sources of human diseases. Far fewer the other way around.

Part one. Humans as transporters of plant disease? Yes, there’s some evidence.

• Process by which humans can spread diseases to plants is through fomites, i.e. carrying plant disease-causing agents on their person and depositing them on the plants which, if susceptible, could develop disease.
• This is a well-known mechanism of inter-species and/or -kingdom transfer of disease agents. For example, in research institutes that use animals, entry is limited to restricted personnel who need to wear Personal protective equipment (PPE) before they enter areas where animals are housed. This is to minimize spread of human-to-animal diseases and vice-versa. Same procedure is in place in plant research stations.
• Wheat rust is an example of humans spreading plant disease. Since 1970, human-borne rust has been implicated as the source in at least two outbreaks of Wheat leaf rust in Australia (1).

Part two. Common disease agents of humans and plants? Yes, but not yet for transfer of human-to-plant disease.

• Fusarium solani is a filamentous fungus found the world over.
• Species within it are designated FSSC for Fusarium solani species complex.
• Within this complex, FSSC 1 is unique since it includes examples that cause diseases in both humans and plants (2, 3, 4).
• FSSC 1 can infect most Cucurbita fruits (squash, pumpkin, etc), with reports of infected fruits from California and Ohio in USA, and New Zealand and Japan (5).
• Similarly, Klebsiella species that cause diseases in humans have been shown capable of growing on plant tissues. For example, on the surface of potatoes and lettuce (6)

However, no evidence yet that infected humans transmit same disease to plants, making them ‘sick’ in turn (7).

Bibliography

1. Hodson, D. P. “Shifting boundaries: challenges for rust monitoring.” Euphytica 179.1 (2011): 93-104.
2. Chang, Douglas C., et al. “Multistate outbreak of Fusarium keratitis associated with use of a contact lens solution.” Jama 296.8 (2006): 953-963. Page on researchgate.net
3. Zhang, Ning, et al. “Members of the Fusarium solani species complex that cause infections in both humans and plants are common in the environment.” Journal of Clinical Microbiology 44.6 (2006): 2186-2190. Members of the Fusarium solani Species Complex That Cause Infections in Both Humans and Plants Are Common in the Environment
4. O’Donnell, Kerry, et al. “Phylogenetic diversity and microsphere array-based genotyping of human pathogenic fusaria, including isolates from the multistate contact lens-associated US keratitis outbreaks of 2005 and 2006.” Journal of clinical microbiology 45.7 (2007): 2235-2248. Page on asm.org
5. Mehl, H. L., and Lynn Epstein. “Sewage and community shower drains are environmental reservoirs of Fusarium solani species complex group 1, a human and plant pathogen.” Environmental microbiology 10.1 (2008): 219-227. Page on ucanr.edu
6. Knittel, Martin D., et al. “Colonization of the botanical environment by Klebsiella isolates of pathogenic origin.” Applied and environmental Microbiology 34.5 (1977): 557-563. Page on asm.org
7. Melotto, Maeli, Shweta Panchal, and Debanjana Roy. “Plant innate immunity against human bacterial pathogens.” Frontiers in microbiology 5 (2014). Plant innate immunity against human bacterial pathogens

https://www.quora.com/What-are-some-human-borne-viruses-bacteria-that-could-kill-plants-by-contamination/answer/Tirumalai-Kamala

What equipment do you need to measure bacteria levels in food?

Tags

DNATrek, IEH (Institute for Environmental Health), Mansour Samadpour, PCR (Polymerase Chain Reaction)

I read an article recently that suggests a food safety angle may also be pertinent for answering this question. With the distance between farm and fork only increasing by the day, how to be sure that the food we eat is safe?

Even as more of our food needs monitoring to ensure public health safety, the regulators tasked to do it have fewer resources to do it. Enter private enterprise such as IEH Laboratories (Institute for Environmental Health; 1). A New York Times article (2) profiles it and its founder, Mansour Samadpour. That cheap technology proliferated in recent years is a boon, especially for such food safety detectives, who use DNA tests, chemical analyses, and genetic fingerprinting to detect and measure bacteria in food, among other things. Large retailers such as the US warehouse giant Costco depend on companies like IEH to ensure safety of the food they sell.

Not all bacteria are pathogens. Food safety requires detection of only  relevant pathogens. Those are the ones IEH looks for. More details:

From http://www.iehinc.com/wp-content…

To do these tests, one needs bacteriological incubators, specialized culture media to grow these individual bacterial species, consumables such as petridishes, infrastructure such as lab space  and biosafety hoods. Also PCR (Polymerase Chain Reaction) machines and consumables to run PCR tests for pathogen DNA fingerprinting.

Another private food safety company profiled in the same article is DNATrek (3). They claim to be able to track the source of pathogen in food ‘within an hour’ using a new test called DNATrax which detects tracer DNA present in liquid coating applied to many types of produce after harvest or added to prepared foods, giving them a unique genetic fingerprintthat helps identify the ‘specific field or packer or distributor’.

Resources:

1. IEH Laboratories and Consulting Group
2. The New York Times
3. My Site

Are there tricks to get bacteria to uptake nanoparticles?

Tags

Dendrimers, Liposomes, Nanoparticle, Polyanionic nanoparticles, Solid Lipid nanoparticles

Answer by Tirumalai Kamala:

Several types of nanoparticles, namely, liposomes, polymeric nanoparticles, solid lipid nanoparticles, dendrimers, appear to be taken up by bacteria. These structures have been explored mainly for their capacity to more efficiently deliver antibiotics. I highlight the few studies that directly compared bacterial uptake/activity of ‘nanoparticled’ cargo versus cargo alone. Key details that enhance bacterial nanoparticle uptake are italicized.

From 1

Liposomes
Liposomes are small spherical vesicles with phospholipid bilayer walls, usually composed of an amphipathic lipid such as phosphatidylcholine. Incorporating cholesterol increases the membrane’s rigidity. Liposomes encapsulate an aqueous space ranging from about 30 to 10000 nm in diameter.

From 2

Liposomes directly fuse with bacterial membranes, releasing their contents either within the bacterial cell membranes or into its interior. This can improve antibiotic delivery into the bacterial cells, side-stepping bacterial drug-resistance mechanisms such as bacterial membrane impermeability/low permeability or efflux systems (3).

From 1

Cationic liposome formulations bind more efficiently to skin-associated bacteria, Staphylococcus epidermidis and Proteus vulgaris (4).

Liposome-encapsulated oleic acid was bactericidal against MRSA at a 12-fold lower concentration (5) compared to free oleic acid.

Liposome-encapsulated Polymyxin B or vancomycin and teichoplanin had better antibacterial activity against drug-resistant Pseudomonas aeruginosa and MRSA, respectively (1). These liposomes also caused bacterial membrane lipid deformation suggesting they fused with it.

Skin-associated Propionibacterium acnes (P. acnes). Lauric acid, a free fatty acid showed stronger anti-bacterial activity compared to palmitic and lauric acid. However, lauric acid is poorly water soluble, which limits its use in acne treatment. A study of lauric acid liposome formulation (LipoLA) showed it fused with P. acnes membranes, releasing lauric acid within and killing the bacteria (6).

Metal liposomes: Metal matters. Platinum, zinc and titanium enter bacteria, gold doesn’t.
Wang et al made 16 nm gold nanospheres stabilized with citrate ions, which adhered well with the Salmonella typhimurium surface but were unable to get into the bacteria (7). A comparison of gold and platinum nanoparticles (8) showed the former interacted with Salmonella enteritidis but did not get inside, whereas platinum nanoparticles were observed inside the bacteria.
Using flow cytometry (9), dynamic light scattering and transmission electron microscopy (10), Ashutosh et al found that Salmonella typhimurium directly uptake zinc and titanium nanoparticles.

Key detail? A mammalian liver component called S9 enhances this metal nanoparticle uptake by bacteria. Experimental studies used either rat- or mouse-liver derived fraction S9. What is the role of this liver S9 fraction? It could supplement metabolic enzymes such as cytochrome P450 (10), enhance the formation of nanoparticle micelles facilitating uptake (11) or serve as a protein coating for the nanoparticles, again facilitating uptake (12).

I won’t cover silver nanoparticles since ionic silver is largely toxic to bacteria, and used as an antimicrobial agent itself.

Polymeric nanoparticles
Zhang, L., et al. (1) describe the advantages of polymeric nanoparticles for bacterial delivery

1. They are structurally stable and can be synthesized with greater size precision.
2. They have functional groups that can be chemically modified. Lectin, a protein that binds to bacterial cell wall carbohydrates, is frequently used for targeted antimicrobial delivery of polymeric nanoparticles. Lectin-conjugated polymeric nanoparticles containing gliadin specifically bound to Helicobacter pylori cell wall carbohydrate receptors and released the antimicrobial agent into the bacteria (13).

Zhang et al describe two major types of polymeric nanoparticles for antimicrobial drug delivery. One is formed via spontaneous self-assembly of diblock copolymers consisting of hydrophilic and hydrophobic parts. The hydrophobic part forms the polymeric core holding the cargo while the hydrophilic part protects the core from degradation. The length of the hydrophobic chain controls the rate of cargo release. Biodegradable polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), poly(lactide-co-glycolide) (PLGA), poly (?-carprolactone) (PCL), and poly(cyano- acrylate) (PCA) are used to form the hydrophobic polymeric core, while polyethylene glycol (PEG) is most commonly used as the hydrophilic part. The hydrophobic nature of the nanoparticle core allows polymeric nanoparticles to carry and deliver poorly water soluble cargo.

In the other type of polymeric nanoparticle, linear polymers such as polyalkyl acrylates and polymethyl methacrylates form nanocapsules by emulsion polymerization. The cargo, antibiotics for example, are either absorbed or covalently conjugated to the nanoparticle surface.The caveat with covalent linkage is the need to empirically assess case-by-case whether the linkage inactivates cargo activity. For example, Abeylath et al found that covalent linkage inactivated penicillin but not beta-lactam or ciprofloxacin (14).

Nanoparticles using poly (lactide-co-glycolide) [PLGA] loaded with antibiotics such as gentamicin (15), azithromicin and clarithromicin (16, 17) were more effective than corresponding intact antibiotic against Salmonella typhimurium. It’s possible this is due to such nanoparticles adhering better to the bacteria. Dillen et al reported adhesion of PLGA containing cationic Eudragit nanoparticles to S. aureus (18). Bacterial cell walls tend to be negatively charged (19) so exploiting such electrostatic interactions helps bacterial nanoparticle uptake (20). PLGA has many other advantages including low toxicity, cargo flexibility, easy synthesis, precision engineering for surface properties (20).

Solid lipid nanoparticles
Lipid + surfactants for emulsification. Lipids can be free fatty acids such as palmitic, decanoic or behenic acids, or triglycerides such as trilaurin, trimyristin, or tripalmitin, or steroids such as cholesterol. Emulsifiers include soybean lecithin, phosphatidylcholine. Solid lipid nanoparticles have many advantages over other nanoparticles including greater cargo stability, bothhydrophilic and lipophilic cargo can be loaded, no need for organic solvents, greater precision in controlled cargo release and targeting,  and improved bulk production.

Dendrimer
A dendrimer is a polymer structure with enhanced surface area-to-volume ratio owing to extensive branching around a core unit. When a dendrimer has a high concentration of positively charged quaternary ammonium compounds on its surface, they bind more efficiently to negatively charged microbial cell walls. This increases bacterial membrane permeability, letting more dendrimers inside the bacteria (1, 21).

I could not find a single study that directly compared cargo alone versus solid lipid nanoparticle- or dendrimer-encapsulated cargo uptake by bacteria.

Bibliography

1. Zhang, L., et al. “Development of nanoparticles for antimicrobial drug delivery.” Current medicinal chemistry 17.6 (2010): 585-594 Page on ucsd.edu
2. Nokhodchi, Ali, Ghobad Mohammadi, and Taravat Ghafourian. Nanotechnology tools for efficient antibacterial delivery to Salmonella. INTECH Open Access Publisher, 2012 Page on intechweb.org
3. Mugabe, Clement, et al. “Mechanism of enhanced activity of liposome-entrapped aminoglycosides against resistant strains of Pseudomonas aeruginosa.” Antimicrobial agents and chemotherapy 50.6 (2006): 2016-2022 Mechanism of Enhanced Activity of Liposome-Entrapped Aminoglycosides against Resistant Strains of Pseudomonas aeruginosa
4. Robinson, Anne M., et al. “The interaction of phospholipid liposomes with mixed bacterial biofilms and their use in the delivery of bactericide.” Colloids and Surfaces A: Physicochemical and Engineering Aspects 186.1 (2001): 43-53.
5. Huang, Chun-Ming, et al. “Eradication of drug resistant Staphylococcus aureus by liposomal oleic acids.” Biomaterials 32.1 (2011): 214-221 Page on nih.gov
6. Yang, Darren, et al. “The antimicrobial activity of liposomal lauric acids against Propionibacterium acnes.” Biomaterials 30.30 (2009): 6035-6040.  Page on nih.gov
7. Wang, Shuguang, et al. “Toxic effects of gold nanoparticles on Salmonella typhimurium bacteria.” Toxicology and industrial health (2011): 0748233710393395 Page on nih.gov
8. Sawosz, Ewa, et al. “Visualization of gold and platinum nanoparticles interacting with Salmonella enteritidis and Listeria monocytogenes.” International journal of nanomedicine 5 (2010): 631 Page on nih.gov
9. Kumar, Ashutosh, et al. “A flow cytometric method to assess nanoparticle uptake in bacteria.” Cytometry Part A 79.9 (2011): 707-712 Page on wiley.com
10. Kumar, Ashutosh, et al. “Cellular uptake and mutagenic potential of metal oxide nanoparticles in bacterial cells.” Chemosphere 83.8 (2011): 1124-1132 Page on researchgate.net
11. Sereemaspun, A., et al. “Inhibition of Human Cytochrome P450 Enzymes by Metallic Nanoparticles: A preliminary to Nanogenomics.” International Journal of Pharmacology 4.6 (2008).
12. Romberg, Birgit, Wim E. Hennink, and Gert Storm. “Sheddable coatings for long-circulating nanoparticles.” Pharmaceutical research 25.1 (2008): 55-71 Sheddable Coatings for Long-Circulating Nanoparticles
13. Umamaheshwari, R. B., and N. K. Jain. “Receptor mediated targeting of lectin conjugated gliadin nanoparticles in the treatment of Helicobacter pylori.” Journal of drug targeting 11.7 (2003): 415-424.
14. Abeylath, Thotaha Wijayahewage Sampath Chrysantha. “Glyconanobiotics: Novel carbohydrated nanoparticle polymers.” (2007) http://scholarcommons.usf.edu/cg…
15. Ranjan, Ashish, et al. “Antibacterial efficacy of core-shell nanostructures encapsulating gentamicin against an in vivo intracellular Salmonella model.” International journal of nanomedicine 4 (2009): 289 Page on nih.gov
16. Mohammadi, Ghobad, et al. “Development of azithromycin–PLGA nanoparticles: Physicochemical characterization and antibacterial effect against Salmonella typhi.” Colloids and Surfaces B: Biointerfaces 80.1 (2010): 34-39.
17. Mohammadi, Ghobad, et al. “Physicochemical and anti-bacterial performance characterization of clarithromycin nanoparticles as colloidal drug delivery system.” Colloids and Surfaces B: Biointerfaces 88.1 (2011: 39-44).
18. Dillen, Kathleen, et al. “Adhesion of PLGA or Eudragit®/PLGA nanoparticles to Staphylococcus and Pseudomonas.” International journal of pharmaceutics 349.1 (2008): 234-240.
19. Al-Kobaisi, Muhannad F. “Jawetz, Melnick & Adelberg’s Medical Microbiology.” Sultan Qaboos University Medical Journal 7.3 (2007): 273.
20. Radovic-Moreno, Aleksandar F., et al. “Surface charge-switching polymeric nanoparticles for bacterial cell wall-targeted delivery of antibiotics.” ACS nano 6.5 (2012): 4279-4287 Page on nih.gov
21. Huh, Ae Jung, and Young Jik Kwon. ““Nanoantibiotics”: a new paradigm for treating infectious diseases using nanomaterials in the antibiotics resistant era.” Journal of Controlled Release 156.2 (2011): 128-145.

Are there tricks to get bacteria to uptake nanoparticles?