Translocation of Pseudomonas aeruginosa from the intestinal tract is mediated by the binding of ExoS to an Na, K-ATPase regulator, FXYD3.
Summary of "Translocation of Pseudomonas aeruginosa from the intestinal tract is mediated by the binding of ExoS to an Na, K-ATPase regulator, FXYD3."
The intestinal tract is considered the most important reservoir of Pseudomonas aeruginosa in intensive care units. 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. Translocation of endogenous P. aeruginosa from the colonized intestinal tract is an important pathogenic phenomenon. We identify here 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, is 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 andfor bacterial translocation from the midgut to the hemolymph. Using a bacterial two-hybrid screen, we show that the mammalian factor, FXYD3, which co-localizes with and regulates the function of Na, K-ATPase, directly binds ExoS. A pull-down 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.
Affiliation
Department of Microbiology and Infection Control Science, and Educational and Research Center for Clinical Pharmacy, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414, Japan.
Journal Details
This article was published in the following journal.
Name: Infection and immunity
ISSN: 1098-5522
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20805335
- DOI: http://dx.doi.org/10.1128/IAI.00428-10
Medical and Biotech [MESH] Definitions
Pseudomonas Aeruginosa
A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection.
Bacterial Translocation
The passage of viable bacteria from the gastrointestinal tract to extra-intestinal sites, such as the mesenteric lymph node complex, liver, spleen, kidney, and blood. Factors that promote bacterial translocation include overgrowth with gram-negative enteric bacilli, impaired host immune defenses, and injury to the intestinal mucosa resulting in increased intestinal permeability. These mechanisms can act in concert to promote synergistically the systemic spread of indigenous translocating bacteria to cause lethal sepsis.
Pyocyanine
Antibiotic pigment produced by Pseudomonas aeruginosa.
Eikenella Corrodens
Gram-negative bacteria isolated from infections of the respiratory and intestinal tracts and from the buccal cavity, intestinal tract, and urogenital tract. They are probably part of the normal flora of man and animals.
Pyocins
Bacteriocins elaborated by mutant strains of Pseudomonas aeruginosa. They are protein or protein-lipopolysaccharide complexes lethal to other strains of the same or related species.
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