Classical Vaccine Development Suggests Pathogenic To Probiotic Conversion Of Bacteria Is Theoretically Possible
Classical vaccine development includes, i.e., rendering a live pathogenic bacteria relatively harmless through the process of attenuation.
Starting in the late 19th century when scientists first succeeded in growing bacteria in culture, they attempted to generate live attenuated versions of a variety of pathogenic bacteria through their prolonged culture. A prominent success includes the live TB vaccine,, from the pathogenic cow TB microbe, Mycobacterium bovis.
and ( )
‘heroically sub-cultured this bacterium every 3 weeks in their special glycerin-potato medium, adding ox bile to the mix when they noticed their bacterial cultures tended to clump, which fortuitously led to a reduction in virulence. Why heroically? Heroic because they continued their sub-cultures unabated through the German occupation of Lille, even through increasing scarcity of potato and ox bile! By 1919, after about 230 subcultures over 11 years, they had in their hands a tubercle bacillus that did not cause TB in guinea pigs, rabbits, cattle, or horses (). Starting in 1921 and continuing to date, it’s estimated that more than 5 billion people got the BCG vaccine.‘
See figure below for examples of attenuated bacteria including Salmonella enterica serovar typhi and Vibrio cholerae, causative agents of typhoid and cholera, respectively (3).
Some Natural Examples Of Bacteria That Span The Spectrum From Probiotic To Pathogen
The WHO defines probiotic bacteria as ‘live microorganisms which when administered in adequate amounts confer a health benefit on the host‘ (). Depending on the context, C. butyricum and H. pylori can be either beneficial or pathogenic.
Widely used in China, Japan, Korea,, a strictly anaerobic, Gram-positive, sporulating bacillus, fits the definition of a probiotic (5, , 7). For e.g., the C. butyricum probiotic strain, CBM588, effectively treated and prevented antibiotic-associated diarrhea in children (8). It apparently worked by increasing anaerobes and by preventing the decrease of Bifidobacterium species in antibiotic-Rx children, i.e., by the well-known probiotic/beneficial mocrobe mechanism of .
However, C. butyricum is associated in the context of disease as well ().
- Other C. butyricum strains have been found in infant botulism in Italy (10), China, India, Ireland and the US ( ).
- Other C. butyricum strains have been found in NEC ( ), an extremely dangerous gastrointestinal disease that disproportionately affects preterm newborns (12, , ).
- A different C. butyricum strains was found in an elderly patient with antibiotic-associated diarrhea ( ).
What gives? How could a microbe be safely consumed as a probiotic in some countries, as C. butyricum is in China, Japan and Korea and yet be associated with deadly diseases in other countries? Molecular analyses of pathogenic C. butyricum strains isolated from patients suggests acquisition of virulence factors such as enterotoxins and botulinum neurotoxin (see figure below from (). However, the triggers that drive expression of beneficial or pathological traits are as yet completely unknown as culture of such strictly anaerobic bacterial strains continues to be extremely challenging.
Estimated to infect >50% of the global human population (), the Gram-negative H. pylori also walks the spectrum all the way from pathogenicity to mutualism (see figures below from ). H. pylori pathogenicity ensues from a complex interaction between microbial expression of virulence factors such as VacA and Cag A for e.g., and genetic predisposition among different ethnicities ( , ).
Examples such as C. butyricum and H. pylori suggest that selection pressure imposed by human actions such as migration, dense populations and excessive antibiotic use contribute to the likelihood whether such highly prevalent microbes express pathogenic features or not.
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