The Interplay between Two Transcriptional Repressors and Chaperones Orchestrates Helicobacter pylori Heat-Shock Response

Abstract

The ability to gauge the surroundings and modulate gene expression accordingly is a crucial feature for the survival bacterial pathogens. In this respect, the heat-shock response, a universally conserved mechanism of protection, allows bacterial cells to adapt rapidly to hostile conditions and to survive during environmental stresses. The important and widespread human pathogen Helicobacter pylori enrolls a collection of highly conserved heat-shock proteins to preserve cellular proteins and to maintain their homeostasis, allowing the pathogen to adapt and survive in the hostile niche of the human stomach. Moreover, various evidences suggest that some chaperones of H. pylori may play also non-canonical roles as, for example, in the interaction with the extracellular environment. In H. pylori, two dedicated transcriptional repressors, named HspR and HrcA, homologues to well-characterized regulators found in many other bacterial species, orchestrate the regulation of heat-shock proteins expression. Following twenty years of intense research, characterized by molecular, as well as genome-wide, approaches, it is nowadays possible to appreciate the complex picture representing the heat-shock regulation in H. pylori. Specifically, the HspR and HrcA repressors combine to control the transcription of target genes in a way that the HrcA regulon results embedded within the HspR regulon. Moreover, an additional level of control of heat-shock genes’ expression is exerted by a posttranscriptional feedback regulatory circuit in which chaperones interact and modulate HspR and HrcA DNA-binding activity. This review recapitulates our understanding of the roles and regulation of the most important heat-shock proteins of H. pylori, which represent a crucial virulence factor for bacterial infection and persistence in the human host.

Cooperative Regulation of Campylobacter jejuni Heat-Shock Genes by HspR and HrcA

“…In the human pathogen H. pylori , chaperones genes’ regulation by HspR and HrcA is built on an almost identical circuitry to the one here drawn for C. jejuni , where the regulon of HrcA appears to be entirely enclosed within the HspR regulon [ 36 ]. However, in H. pylori the two regulatory proteins bind to their operators in an independent manner and do not display any direct protein–protein interaction [ 13 , 37 ]. Indeed, in a previous work by our group, we assayed the DNA binding activities of HspR and HrcA under the same competitive conditions used in this work for the homologous regulators of C. jejuni .…”

Resistance of Listeria monocytogenes to Stress Conditions Encountered in Food and Food Processing Environments

“…This allows binding of RNA polymerase-σ 32 to the promoters of clp genes inducing the transcription of clpC and clpP . Following temperature-dependent autophosphorylation, McsB, assisted by McsA, targets CtsR to degradation by ClpCP protease (based on Krüger et al, 2001 ; Roncarati and Scarlato, 2017 ; Roncarati and Scarlato, 2018 ).…”

Helicobacter pylori Virulence Factor Cytotoxin-Associated Gene A (CagA)-Mediated Gastric Pathogenicity

“…In response to a sudden temperature increase, bacterial cells promptly induce the expression of a group of proteins knows as heat-shock proteins (HSPs). The HSPs are crucial for cellular protection, survival, and adaptation to adverse environmental conditions [ 112 ]. Several studies have demonstrated the role of heat shock protein 1 (HSP1) in stabilizing the persistent infection mediated by CagA [ 113 , 114 ].…”