title: Virulence is positively selected by transmission success between mammalian hosts.
abstract: Virulence, defined as damage to the host, is a trait of pathogens that evolutionary theory suggests benefits the pathogen in the "struggle for existence". Pathogens employ virulence mechanisms that contribute to disease. Central to the evolution of virulence of the infectious agents causing an array of bacterial disease is the evolutionary acquisition of type III secretion, a macromolecular complex that creates a syringe-like apparatus extending from the bacterial cytosol to the eukaryotic cytosol and delivers secreted bacterial virulence factors (effectors) into host cells. In this work, we quantify the contribution of virulence determinants to the evolutionary success of a pathogen. Using a natural pathogen of mice, we show that virulence factors provide a selective advantage by enhancing transmission between hosts. Virulence factors that have a major contribution to disease were absolutely required for transmission of the pathogen to naive hosts. Virulence-factor mutants with more subtle defects in pathogenesis had quantifiable roles in the time required to transmit the pathogen between mice. Virulence-factor mutants were also found to lose in competition with wild-type bacteria when iteratively transmitted from infected to uninfected mice. These results directly demonstrate that virulence is selected via the fitness advantage it provides to the host-to-host cycle of pathogenic species.
authors: Michael Smith Laboratories, University of British Columbia, 301-2185 East Mall, Vancouver, British Columbia V6T 1Z4, Canada.
authors: Mark E
authors: ME
authors: Wickham
authors: Nat F
authors: NF
authors: Brown
authors: Erin C
authors: EC
authors: Boyle
authors: Brian K
authors: BK
authors: Coombes
authors: B Brett
authors: BB
authors: Finlay
mesh_terms: D000818:Animals; D005075:Biological Evolution; D044082:Citrobacter rodentium / Q000235:genetics / Q000472:pathogenicity*; D018562:Disease Transmission, Infectious; D004756:Enterobacteriaceae Infections / Q000635:transmission*; D051379:Mice; D012641:Selection, Genetic; D013997:Time Factors; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D037521:Virulence Factors