Abstract
Yersinia pestis, the causative agent of plague, has a complex infectious cycle that alternates between mammalian hosts (rodents and humans) and insect vectors (fleas). Consequently, it must adapt to a wide range of host environments to achieve successful propagation. Y. pestis PhoP is a response regulator of the PhoP/PhoQ two-component signal transduction system that plays a critical role in the pathogen’s adaptation to hostile conditions. PhoP is activated in response to various host-associated stress signals detected by the sensor kinase PhoQ and mediates changes in global gene expression profiles that lead to cellular responses. Y. pestis PhoP is required for resistance to antimicrobial peptides, as well as growth under low Mg2+ and other stress conditions, and controls a number of metabolic pathways, including an alternate carbon catabolism. Loss of phoP function in Y. pestis causes severe defects in survival inside mammalian macrophages and neutrophils in vitro, and a mild attenuation in murine plague models in vivo, suggesting its role in pathogenesis. A Y. pestis phoP mutant also exhibits reduced ability to form biofilm and to block fleas in vivo, indicating that the gene is also important for establishing a transmissible infection in this vector. Additionally, phoP promotes the survival of Y. pestis inside the soil-dwelling amoeba Acanthamoeba castellanii, a potential reservoir while the pathogen is quiescent. In this review, we summarize our current knowledge on the mechanisms of PhoP-mediated gene regulation in Y. pestis and examine the significance of the roles played by the PhoP regulon at each stage of the Y. pestis life cycle.
Highlights
Yersinia pestis, a gram-negative bacterium that causes plague, emerged as a subclone of Yersinia pseudotuberculosis as recently as 5000–6000 years ago [1,2,3,4]
We summarize our current knowledge on the signals that activate Y. pestis PhoP in different host environments, the genes and molecular pathways that are regulated by PhoP, and different ways by which the PhoP regulon contributes to the adaptation of Y. pestis to various stages of its life cycle
Tracking studies have shown that Y. pestis reaches draining lymph nodes as quickly as 10 min after intradermal inoculation, without using macrophages and neutrophils as carriers [43], suggesting that these cells are not required for trafficking or the pathogenesis of Y. pestis
Summary
A gram-negative bacterium that causes plague, emerged as a subclone of Yersinia pseudotuberculosis as recently as 5000–6000 years ago [1,2,3,4]. To decrease the binding of the positively-charged CAMPs, Y. pestis uses the gene products of the PhoP-regulated pmrHFIJKLM ( termed arnBCADTEF or pbgP operon) and ugd ( termed pmrE) genes to add a 4-aminoarabinose to the lipid A, thereby neutralizing the negative charge of the outer membrane [21,22]. Another phoP-regulated gene, pagP, encodes a lipopolysaccharide (LPS) modifying enzyme that mediates the transfer of a palmitate group to the lipid A in Y. pseudotuberculosis and Yersinia enterocolitica.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
