Transcriptome analysis of the Mg2+-responsive PhoP regulator in Yersinia pestis

PhoP was previously shown to be important for Yersinia pestis survival in macrophage and under macrophage-induced stresses. In this work, a phoP disruptant of Y pestis 201 was generated using the Red cloning procedure. The transcription profile of the wildtype Y pestis was then compared with that of the phoP mutant under Mg2+-limiting conditions. It was revealed that PhoP/PhoQ governed a wide set of cellular pathways in Y pestis, especially including the positive regulation of many metabolic processes, Mg2+ transport, peptidoglycan remodeling, lipopolysaccharide (LPS) modification and various stress-protective functions. The Mg2+ transport system regulated by PhoP may make Y pestis to maintain the magnesium homeostasis under low Mg2+ environments. The PhoP-controlled stress-protective functions likely constitute the molecular basis for the observation that mutation of the phoP gene rendered the bacteria more sensitive to various macrophage-induced stresses. Modification of LPS mediated by PhoP is hypothesized to not only neutralize negative charges as normally done by Mg2+ ions, but also mediate the resistance of Y pestis to antimicrobial peptides. The microarray results provide a population of candidate genes or pathways, and further biochemical experiments are needed to elucidate the PhoP-dependent mechanisms by which Y pestis survives the antibacterial strategies employed by host macrophages. (c) 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved.