Affiliation:
1. Department of Microbiology and Infection Control Science
2. Educational and Research Center for Clinical Pharmacy, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, Japan
Abstract
ABSTRACT
The intestinal tract is considered the most important reservoir of
Pseudomonas aeruginosa
in intensive care units (ICUs). Gut colonization by
P. aeruginosa
underlies the development of invasive infections such as gut-derived sepsis. Intestinal colonization by
P. aeruginosa
is associated with higher ICU mortality rates. The translocation of endogenous
P. aeruginosa
from the colonized intestinal tract is an important pathogenic phenomenon. Here we identify bacterial and host proteins associated with bacterial penetration through the intestinal epithelial barrier. We first show by comparative genomic hybridization analysis that the
exoS
gene, encoding the type III effector protein, ExoS, was specifically detected in a clinical isolate that showed higher virulence in silkworms following midgut injection. We further show using a silkworm oral infection model that
exoS
is required both for virulence and for bacterial translocation from the midgut to the hemolymph. Using a bacterial two-hybrid screen, we show that the mammalian factor FXYD3, which colocalizes with and regulates the function of Na,K-ATPase, directly binds ExoS. A pulldown assay revealed that ExoS binds to the transmembrane domain of FXYD3, which also interacts with Na,K-ATPase. Na,K-ATPase controls the structure and barrier function of tight junctions in epithelial cells. Collectively, our results suggest that ExoS facilitates
P. aeruginosa
penetration through the intestinal epithelial barrier by binding to FXYD3 and thereby impairing the defense function of tight junctions against bacterial penetration.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Immunology,Microbiology,Parasitology
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