Maintaining Integrity Under Stress: Envelope Stress Response Regulation of Pathogenesis in Gram-Negative Bacteria - PubMed (original) (raw)

Review

Maintaining Integrity Under Stress: Envelope Stress Response Regulation of Pathogenesis in Gram-Negative Bacteria

Claire L Hews et al. Front Cell Infect Microbiol. 2019.

Abstract

The Gram-negative bacterial envelope is an essential interface between the intracellular and harsh extracellular environment. Envelope stress responses (ESRs) are crucial to the maintenance of this barrier and function to detect and respond to perturbations in the envelope, caused by environmental stresses. Pathogenic bacteria are exposed to an array of challenging and stressful conditions during their lifecycle and, in particular, during infection of a host. As such, maintenance of envelope homeostasis is essential to their ability to successfully cause infection. This review will discuss our current understanding of the σE- and Cpx-regulated ESRs, with a specific focus on their role in the virulence of a number of model pathogens.

Keywords: Cpx response; Gram-negative bacteria; envelope stress; pathogenesis; sigmaE response.

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Figures

Figure 1

Figure 1

Regulated intramembrane proteolysis (RIP) leads to activation of the σE ESR. In the presence of misfolded proteins, a conformational change as a result of misfolded proteins binding to the PDZ domain of DegS occurs. Subsequently the protease domain of DegS is exposed and the periplasmic domain of RseA is cleaved. RseP then cleaves RseA at the cytoplasmic domain, releasing the σE-bound RseA portion into the cytoplasm. Binding of the adaptor protein SspB to RseA-σE recruits the ClpXP protease for degradation of RseA and release of free σE. σE binds to RNA polymerase and transcription of the σE regulon is induced.

Figure 2

Figure 2

The sRNAs MicL, RybB, and MicA exert control over OM homeostasis and the σE envelope stress response. The presence of misfolded OMPs activates the σE ESR through a proteolytic cleavage cascade as described in Figure 1. The σE regulon includes the Hfq-associating sRNAs micL, rybB, and micA. MicL inhibits lpp mRNA translation leading to a reduction in Lpp production. RybB and MicA reduce ompC and ompW mRNA levels, reducing the flux of uOMPs into the periplasm during stress and σE inducing conditions. Normal arrows represent positive regulation and blunt arrows indicate negative regulation. Dashed lines indicate where regulation is indirect and/or where intermediate factors are unknown.

Figure 3

Figure 3

σE-regulation of virulence factors in Escherichia coli, Salmonella enterica, and Pseudomonas spp. The σE ESR regulates many virulence factors and surface structures, such as adhesins, in multiple bacteria such as Salmonella enterica (A), E. coli (B), and Pseudomonas spp. (C), primarily via the upregulation of periplasmic folding factors. Additionally, a number of bacteria-specific factors are regulated by this ESR. These include hydrogen cyanide in Pseudomonas sp. and the Salmonella pathogenicity islands (SPIs), SPI-1, and SPI-2. Normal arrows represent positive regulation and blunt arrows indicate negative regulation. Dashed lines indicate where regulation is indirect and/or where intermediate factors are unknown.

Figure 4

Figure 4

The Cpx response senses and responds to a variety of envelope stresses. Proposed inducing cues of the Cpx response are shown with red arrows and corresponding red lettering: (A) stresses that lead to protein misfolding; (B) damage to peptidoglycan; (C) surface signals; (D) monitoring periplasmic redox states; (E) OM lipoprotein trafficking defects. In the absence of induction, the phosphatase activity of CpxA keeps CpxR unphphosphorylated. Upon induction, phosphotransfer from phosphorylated CpxA to CpxR leads to CpxR-P modulation of transcription of genes involved in several processes. Genes shown are representative, but not exhaustive of the Cpx regulon.

Figure 5

Figure 5

The Cpx response is involved in the pathogenesis of several Gram-negative bacteria. The Cpx response regulates many different processes related to the pathogenesis of several different organisms, such as Escherichia coli (A), Salmonella enterica (B), Vibrio cholerae (C), and Yersinia spp. (D). Cpx regulation not only regulates the assembly of envelope-localized virulence determinants but also several other processes that impact envelope integrity and affect the ability of bacteria to colonize hosts. Proposed positive regulation is indicated by regular arrows, whereas blunt arrows represent negative regulation. Dashed lines indicate where regulation is indirect.

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