A shift in pH to ~7.5 in the intestinal mucus during physiological stress can lead to activation of multiple siderophore-related genes that directly impact microbial virulence. We show for the first time
that suppression of siderophore-related virulence expression in P. aeruginosa can be achieved without providing iron by creating conditions of local phosphate sufficiency at pH 6.0. These findings may have significant therapeutic implications given that there is reluctance to provide excess iron in the face of life threatening infection. Understanding the local cues that activate virulence of common pathogens that colonize the gut during critical illness may lead to new insight into their pathogenesis. Acknowledgements We thank Selleck LY2603618 Irina Morozova for her technical assistance, Pierre Cornelis for ΔPvdD/ΔPchEF double mutant, and Michael Vasil for permission MK-0457 price to interpret and present his data (Ochsner et al., 2002) in Figure 4 for discussion purposes. We thank Jaejung Kim, Siming Shou, and Ashwin Vishnuvardhana, the University of Chicago Core Functional Genomics Facility for processing and statistical analysis of microarray data. This study was funded by NIH RO1 GM062344-11 (JA). References 1. Shimizu K, Ogura H, Goto M, Asahara T, Nomoto K, Morotomi M, Yoshiya K, Matsushima A, Sumi Y, Kuwagata
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