Affiliation:
1. INSERM U1001, Faculté de Médecine Paris Descartes, Université Paris Descartes, Paris, France
2. INSERM U722, Faculté de Médecine, Université Paris Denis Diderot, Site Xavier Bichat, Paris, France
Abstract
ABSTRACT
The virulence of many human pathogens does not seem to be an evolutionarily selected trait, but an accidental by-product of the selection that operates in another ecological context. We investigated the possibility that virulence of the
ex
traintestinal
p
athogenic
E
scherichia
c
oli
(ExPEC) strains, which frequently cause disease in the host in which they asymptomatically colonize the intestine, is the consequence of commensalism. Most of the ExPEC virulence factors are clustered on genomic islands called
p
athogenicity-
a
ssociated
i
slands (PAIs). We constructed and characterized several mutants of the ExPEC 536 strain with either (i) deletions of each single PAI or (ii) a complete deletion of all seven PAIs.
In vitro
phenotypic characterization of 536 mutants showed that the seven PAIs were dispensable for growth in the absence of external stress, as well as under a range of biologically relevant stressors, i.e., serum, bile, and oxidative, nitrosative, hyperosmotic, and acidic stress. However, challenge against the wild-type (WT) strain in a murine model shows that the deletion of all seven PAIs drastically reduces the fitness of 536 during persistent intestinal colonization. This defect seems to be linked to the hypermotility observed for mutants devoid of all seven PAIs. In addition, we show that PAIs diminish fitness of their carrier during growth in urine, suggesting that urinary tract infections are unlikely to provide selective pressure for the maintenance of ExPEC PAIs. Our results are in accordance with the coincidental-evolution hypothesis postulating that extraintestinal
E. coli
virulence is a by-product of commensalism.
Publisher
American Society for Microbiology
Subject
Molecular Biology,Microbiology
Cited by
102 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献