Incomplete immunity in a natural animal-microbiota interaction selects for higher pathogen virulence

Incomplete immunity in recovered hosts is predicted to favor more virulent pathogens upon re-infection in the population.1Fleming-Davies A.E. Williams P.D. Dhondt A.A. Dobson A.P. Hochachka W.M. Leon A.E. Ley D.H. Osnas E.E. Hawley D.M. Incomplete host immunity favors the evolution of virulence in an emergent pathogen.Science. 2018; 359: 1030-1033Crossref PubMed Scopus (40) Google Scholar The microbiota colonizing animals can generate a similarly long-lasting, partial immune response, allowing for infection but dampened disease severity.2Hoang K.L. King K.C. Symbiont-mediated immune priming in animals through an evolutionary lens.Microbiology. 2022; 168: 1-11Crossref Scopus (2) Google Scholar We tracked the evolutionary trajectories of a widespread pathogen (Pseudomonas aeruginosa), experimentally passaged through populations of nematodes immune-primed by a natural microbiota member (P. berkeleyensis). This bacterium can induce genes regulated by a mitogen-activated protein kinase (MAPK) signaling pathway effective at conferring protection against pathogen-induced death despite infection.3Montalvo-Katz S. Huang H. Appel M.D. Berg M. Shapira M. Association with soil bacteria enhances p38-dependent infection resistance in Caenorhabditis elegans.Infect. Immun. 2013; 81: 514-520Crossref PubMed Scopus (94) Google Scholar Across host populations, this incomplete immunity selected for pathogens more than twice as likely to kill as those evolved in non-primed (i.e., naive) or immune-compromised (mutants with a knockout of the MAPK ortholog) control populations. Despite the higher virulence, pathogen molecular evolution in immune-primed hosts was slow and constrained. In comparison, evolving pathogens in immune-compromised hosts were characterized by substantial genomic differentiation and attenuated virulence. These findings directly attribute the incomplete host immunity induced from microbiota as a significant force shaping the virulence and evolutionary dynamics of novel infectious diseases.