Proc Natl Acad Sci USA 2007,104(7):2109–2114.PubMedCrossRef 99. Sam MD, Papagiannis CV, Connolly KM, Corselli L, Iwahara J, Lee J, Phillips M, Wojciak JM, Johnson RC, Clubb RT: Regulation of directionality in bacteriophage lambda site-specific recombination: structure of the Xis protein. J Mol Biol 2002,324(4):791–805.PubMedCrossRef Authors’ contributions SVR conducted all experiments and ARRY-162 in vitro analyzed data. SRC analyzed data and wrote part of the paper. PU conceived this study, analyzed data, and wrote

part of the paper. All authors contributed in writing the manuscript and approved its final content.”
“Background Pseudomonas aeruginosa is an opportunistic pathogen that is prevalent in the gut of hospitalized patients exposed to antibiotics buy Evofosfamide https://www.selleckchem.com/products/cftrinh-172.html and extreme physiologic stress such as major organ transplantation, injury, and sudden and severe insults [1–3]. P. aeruginosa

is one of the most common causes of severe sepsis and its primary site of colonization and source of subsequent infection is the intestinal tract reservoir [3–5]. In previous work from our laboratory we analyzed multi-drug resistant isolates of Pseudomonas aeruginosa obtained from critically ill patients for their ability to disrupt the intestinal epithelial barrier and cause lethal gut-derived sepsis [6]. In these studies we identified that certain highly virulent and lethal isolates of P. aeruginosa respond to phosphate limitation by expressing outer surface appendages containing the phosphate signaling protein PstS [7]. We hypothesized that such responsiveness of these strains to phosphate limitation might have evolved from exposure to the depleted phosphate conditions present in a physiologically stressed host. We previously measured phosphate concentration in the intestine of mice following surgical injury and discovered that phosphate becomes rapidly depleted in the distal intestinal tract mucosa (cecum) and is associated with enhanced PstS expression in P. aeruginosa colonizing the mouse gut [8]. Further work using the prototype strain PAO1 demonstrated in both C. elegans and mice, that phosphate limitation causes activation of a lethal phenotype in P. aeruginosa that can be attenuated

when local phosphate abundance/sufficiency is created via oral supplementation [9, 10]. Molecular analysis of this response demonstrated Arachidonate 15-lipoxygenase that phosphate limitation activates a lethal phenotype in PAO1 via signaling mechanisms interconnecting phosphate acquisition systems (PstS-PhoB), quorum sensing (MvfR-PQS), and iron acquisition system (pyoverdin). We therefore hypothesized that maintenance of phosphate abundance/sufficiency at sites of P. aeruginosa colonization, such as the distal gut, may be a potential strategy to prevent virulence activation and hence mortality through the course of extreme physiologic stress when local phosphate stores become depleted. Yet another important local microenvironmental cue that might affect the virulence and lethality of strains of P.