How many bac­te­r­ial pathogens in­fect hu­mans?

by Roberto

In ca­sual con­ver­sa­tions, usu­ally when speak­ing with friends about bac­te­r­ial di­ver­sity, I men­tion that only a tiny mi­nor­ity of the Earth's bac­te­ria cause hu­man dis­ease. In that con­text, I used to men­tion that the num­ber of such pathogens was small, a few dozen, per­haps around 100. In us­ing such "off the cuff" es­ti­mates I was not alone. But, oh my, was I off, way off! A pa­per from 2022, by Bartlett et al. en­ti­tled "A com­pre­hen­sive list of bac­te­r­ial pathogens in­fect­ing hu­mans" puts the num­ber at 1513 and grow­ing rapidly, as can be gleaned from the fig­ure.

Fig. 1. Dis­cov­ery curve for bac­te­r­ial hu­man pathogens. Year of first de­scrip­tion is given on the x‑axis and cu­mu­la­tive species num­ber is given on the y‑axis. Source. Fron­tispiece: Strep­to­coc­cus pyo­genes. Source

Are bac­te­ria rapidly evolv­ing path­o­genic­ity? Should this be cause for con­cern? Not re­ally. In­spec­tion of the pa­per quickly pro­vides nu­mer­ous ex­pla­na­tions for the large and grow­ing num­ber of bac­te­ria in­fect­ing hu­mans. For one, mol­e­c­u­lar tools for bac­te­r­ial iden­ti­fi­ca­tion are now widely used in clin­i­cal lab­o­ra­to­ries, lead­ing to the iden­ti­fi­ca­tion of many new bac­te­r­ial species present at in­fected sites. Then there is the au­thors' de­f­i­n­i­tion of a pathogen: "We des­ig­nate a bac­te­r­ial species as path­o­genic to hu­mans if it has been iso­lated from a hu­man ei­ther at the site of symp­to­matic in­fec­tion or in as­so­ci­a­tion with a toxin-me­di­ated ill­ness act­ing at an­other site." Im­por­tantly, they dis­tin­guish be­tween "pu­ta­tive" pathogens if there are fewer than three known cases and "es­tab­lished" pathogens if there are three or more known cases. Three! In short, even an ex­tremely low fre­quency of in­fec­tion still con­fers a bac­terium the la­bel pathogen. OK. But a cur­sory glance at the list of 1513 iden­ti­fied bac­te­r­ial species re­veals the sur­pris­ing pres­ence of fa­mil­iar bac­te­ria that are con­sumed by hu­mans, for ex­am­ple Lac­to­bacil­lus aci­dophilus (yo­gurt) and Bacil­lus sub­tilis (natto). Also in­cluded is Cutibac­terium ac­nes, which de­spite its name is not clearly de­fined as the eti­o­log­i­cal agent of acne, as Christoph pointed out last Mon­day. These are just a few of the sur­pris­ing pathogens on the list.

So yes, there are 1513 named bac­te­r­ial species that have been as­so­ci­ated with hu­man in­fec­tion. This is in­deed an im­por­tant list to have. But I sus­pect that if we were able to pro­duce a his­togram of the num­ber of in­fected hu­mans and plot those 1513 species in de­scend­ing or­der, more than 90% of in­fec­tions would be the re­sult of a much fewer num­ber (per­haps around 100?), with the rest pro­vid­ing a very long tail of bac­te­r­ial species that cause very low num­bers of in­fec­tions. I may be wrong here again; a far as I know, there is no such his­togram though it would be an in­ter­est­ing analy­sis.

The very high num­ber of bac­te­r­ial species in this list, with many of them not usu­ally as­so­ci­ated with hu­man in­fec­tions, brings up the ques­tion of what is the mean­ing of pathogen? In the end, I side with the con­cept put forth by Ar­turo Casade­vall and Li­ise-anne Pirof­ski, in their ar­ti­cle with the provoca­tive ti­tle: "Mi­cro­bi­ol­ogy: Ditch the term pathogen." While they ad­mit that "the term pathogen is un­likely to go away," they re­mind us that dis­ease is al­ways the re­sult of mi­crobe-host in­ter­ac­tions and that con­text is every­thing. "Dis­ease is as much about the host as it is about the mi­crobe." In short, un­like "a rose is a rose is a rose," a pathogen can be a pathogen but need not al­ways be a pathogen.

 

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