The PhoP/PhoQ System and Its Role in Serratia marcescens Pathogenesis

Abstract

Serratia marcescens is able to invade, persist, and multiply inside nonphagocytic cells, residing in nonacidic, nondegradative, autophagosome-like vacuoles. In this work, we have examined the physiological role of the PhoP/PhoQ system and its function in the control of critical virulence phenotypes in S. marcescens . We have demonstrated the involvement of the PhoP/PhoQ system in the adaptation of this bacterium to growth on scarce environmental Mg 2+ , at acidic pH, and in the presence of polymyxin B. We have also shown that these environmental conditions constitute signals that activate the PhoP/PhoQ system. We have found that the two S. marcescens mgtE orthologs present a conserved PhoP-binding motif and demonstrated that mgtE1 expression is PhoP dependent, reinforcing the importance of PhoP control in magnesium homeostasis. Finally, we have demonstrated that phoP expression is activated intracellularly and that a phoP mutant strain is defective in survival inside epithelial cells. We have shown that the Serratia PhoP/PhoQ system is involved in prevention of the delivery to degradative/acidic compartments.

Serratia marcescens arn , a PhoP-Regulated Locus Necessary for Polymyxin B Resistance

“…marcescens PhoPQ has been demonstrated to control critical virulence phenotypes and be involved in the adaptation to growth with scarce Mg 2ϩ and in the presence of PB, which constitute signals to activate the PhoPQ system (27). Here we found that S. marcescens PhoP can sense both Mg 2ϩ and PB to activate the expression of ugd and arn genes, which are involved in LPS synthesis and modification.…”

“…The ability of S. marcescens to survive the killing action of CAPs is clearly important in the pathogenesis of S. marcescens (27). Although some studies revealed that proteases and LPS modification appeared to be necessary for CAP resistance in other bacteria (3,4), the molecular mechanisms underlying the CAP resistance of S. marcescens remain totally unknown.…”

“…The sequences of arnB and arnC were similar to the first and second genes of the arn (or pmr) operon (arnBCADTEF) in Yer-sinia pestis (http://www.ncbi.nlm.nih.gov/nuccore/NC_004088.1 ?reportϭgenbank&fromϭ2110265&toϭ2117676), an enterobacterium phylogenetically more closely related to S. marcescens (27), E. coli, and Salmonella (5,28). Analysis of the amino acid sequences indicated that arnB and arnC may encode bacterial UDP-4-amino-4-deoxy-L-arabinose-oxoglutarate aminotransferase and undecaprenyl phosphate-4-amino-4-deoxy-L-arabinose transferase, respectively.…”

Bacterial Mg2+Homeostasis, Transport, and Virulence

“…The PhoP regulons (i.e., the collections of genes controlled by PhoP) are widely divergent, possibly because of differences in the ecological niches occupied by bacterial species that harbor PhoP/PhoQ homologs. Nonetheless, these regulons share certain features: First, PhoP regulates expression of at least one Mg 2+ transporter gene (92), e.g., mgtA in Escherichia coli and mgtE in Serratia marscecens (5, 61). Second, the PhoP/PhoQ system positively regulates its own transcription in Salmonella (115), E. coli (61), and Yersinia pestis (92), and this seems to be conserved in other enteric species.…”

When Too Much ATP Is Bad for Protein Synthesis

“…The PhoP/PhoQ system is found in a wide range of gram-negative bacterial species [66-73]. Its role in governing the adaptation to low Mg 2+ conditions is conserved within the family Enterobacteriaceae [57].…”