Abstract
BackgroundMulti-drug resistant Pseudomonas aeruginosa nosocomial infections are increasingly recognized worldwide. In this study, we focused on the virulence of multi-drug resistant clinical strains P. aeruginosa against the intestinal epithelial barrier, since P. aeruginosa can cause lethal sepsis from within the intestinal tract of critically ill and immuno-compromised patients via mechanisms involving disruption of epithelial barrier function.MethodsWe screened consecutively isolated multi-drug resistant P. aeruginosa clinical strains for their ability to disrupt the integrity of human cultured intestinal epithelial cells (Caco-2) and correlated these finding to related virulence phenotypes such as adhesiveness, motility, biofilm formation, and cytotoxicity.ResultsResults demonstrated that the majority of the multi-drug resistant P. aeruginosa clinical strains were attenuated in their ability to disrupt the barrier function of cultured intestinal epithelial cells. Three distinct genotypes were found that displayed an extreme epithelial barrier-disrupting phenotype. These strains were characterized and found to harbor the exoU gene and to display high swimming motility and adhesiveness.ConclusionThese data suggest that detailed phenotypic analysis of the behavior of multi-drug resistant P. aeruginosa against the intestinal epithelium has the potential to identify strains most likely to place patients at risk for lethal gut-derived sepsis. Surveillance of colonizing strains of P. aeruginosa in critically ill patients beyond antibiotic sensitivity is warranted.
Highlights
Multi-drug resistant Pseudomonas aeruginosa nosocomial infections are increasingly recognized worldwide
Bacterial isolates Under IRB protocol #11646B, University of Chicago, 35 strains of P. aeruginosa were consecutively obtained from the clinical microbiology laboratory from those selectively screened for gentamicin (Gm) resistance
P. aeruginosa strains were consecutively collected based on their resistance to gentamicin (Gm), most clinical isolates displayed multiple antibiotic resistances to various antibiotics clinical used against P. aerugi
Summary
The purpose of this study was to determine the ability of MDR P. aeruginosa to disrupt epithelial integrity of Caco-2 monolayers and to correlate these findings to other relevant virulence features of P. aeruginosa including adhesiveness, motility, ability to form biofilm, and the presence of specific type III secretion related genes exoU and exoS
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