The Rcs System in Enterobacteriaceae: Envelope Stress Responses and Virulence Regulation

Abstract

The bacterial cell envelope is a protective barrier at the frontline of bacterial interaction with the environment, and its integrity is regulated by various stress response systems. The Rcs (regulator of capsule synthesis) system, a non-orthodox two-component regulatory system (TCS) found in many members of the Enterobacteriaceae family, is one of the envelope stress response pathways. The Rcs system can sense envelope damage or defects and regulate the transcriptome to counteract stress, which is particularly important for the survival and virulence of pathogenic bacteria. In this review, we summarize the roles of the Rcs system in envelope stress responses (ESRs) and virulence regulation. We discuss the environmental and intrinsic sources of envelope stress that cause activation of the Rcs system with an emphasis on the role of RcsF in detection of envelope stress and signal transduction. Finally, the different regulation mechanisms governing the Rcs system’s control of virulence in several common pathogens are introduced. This review highlights the important role of the Rcs system in the environmental adaptation of bacteria and provides a theoretical basis for the development of new strategies for control, prevention, and treatment of bacterial infections.

The Periplasmic Oxidoreductase DsbA Is Required for Virulence of the Phytopathogen Dickeya solani

“…As mentioned previously, we observed an increased content of the transcriptional regulatory protein RcsB, a component of the Rcs system which senses damage or defects within the envelope and regulates the transcriptome to counteract stress. In particular, this system detects outer membrane damage, LPS synthesis defects, peptidoglycan perturbation and the mislocalization of lipoproteins [ 74 ]. The induction of the Rcs system has been reported in the S. enterica dsbA mutant [ 75 ].…”

Hydroxyl Radical Overproduction in the Envelope: an Achilles’ Heel in Peptidoglycan Synthesis

“…In future work, deciphering the protein-protein interaction network of ElyC may reveal its exact role in envelope biology. Furthermore, transcriptomic studies examining the activity of transcription factors related to oxidative stress (e.g., OxyR, SoxR, NsrR) ( 64 – 67 ) or envelope stress (e.g., CpxR, RpoE, RscA) ( 68 – 70 ) may reveal the extent to which the Δ elyC mutant is responding to oxidative damage and envelope stress. Finally, experiments examining the involvement of cytosolic and periplasmic superoxide dismutases or other ROS defenses (e.g., catalases, alkyl hydroperoxide reductases, thiol peroxidase, peroxiredoxin) in the viability of the Δ elyC mutant may also reveal whether other ROS are accumulating in the mutant.…”

Evolutionary analysis in Enterobacterales of the Rcs-repressor protein IgaA unveils two cytoplasmic small β-barrel domains central for function

“…The Rcs system plays a key sensory role in bacteria of the order Enterobacterales for combating insults to their envelope. 1,2 Upon signal perception, the Rcs system is activated by a phosphorelay cascade involving the inner membrane proteins RcsC/RcsD, which transduce the signal to the cytoplasmic transcriptional regulator RcsB. 1 Studies performed mostly in Salmonella enterica serovar Typhimurium (S. Typhimurium) and Escherichia coli have provided compelling evidence for a tight control of the Rcs system under non-stress conditions.…”

“…18.504389 doi: bioRxiv preprint virulence-related factors. 1,2 Ortholog members of the IgaA family characterized to date include UmoB of Proteus miriabilis 9 and GumB of Serratia marcenses. 12 In contrast to S. Typhimurium and E. coli, 3,[5][6][7] the lack of the IgaA orthologs UmoB and GumB does not compromise viability in P. mirabilis or S. marcenses.…”