Affiliation:
1. Department of Molecular Microbiology, Box 8230
2. Division of Pediatric Infectious Diseases, Box 8116, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, Missouri 63110
Abstract
ABSTRACT
In the murine model of urinary tract infections (UTI), cystitis by uropathogenic
Escherichia coli
(UPEC) occurs through an intimate relationship with the bladder superficial umbrella cell entailing cycles of adherence, invasion, intracellular bacterial community (IBC) formation, and dispersal (fluxing) from the intracellular environment. IBC dispersal is a key step that results in the spread of bacteria over the epithelial surface to initiate additional rounds of IBC formation. We investigated the role of flagella in mediating adherence and motility during UTI, hypothesizing that the dispersion of the IBC would be incomplete in the absence of motility, thus interrupting the IBC pathway and attenuating the infection. Using
gfp
reporter fusions, the expression of the flagellar class I
flhDC
and class III
fliC
genes was monitored to track key points of regulation throughout the pathogenic cascade. In vitro, growth under conditions promoting motility resulted in the robust expression of both fusions. In contrast, only the class I fusion produced significant expression throughout early stages of IBC development including the dispersion stage. Thus, unlike in vitro modeling of motility, the regulatory cascade appeared incomplete in vivo. Throughout IBC formation, nonmotile Δ
fliC
mutants achieved the same number of IBCs as the wild-type (
wt
) strain, demonstrating that flagella are neither essential nor required for first- or second-generation IBC formation. However, in competition experiments between
wt
and Δ
fliC
strains, the
wt
was shown to have a fitness advantage in persisting throughout the urinary tract for 2 weeks, demonstrating a subtle but measurable role for flagella in virulence.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
Cited by
191 articles.
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