Chapter 10 : Quorum Sensing in Pathogenesis

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One of the environmental signals measured by is its own cell density, which it achieves by a quorum-sensing mechanism. During inhabitation of aquatic environments, lives in association with various species of phytoplankton and zooplankton, often in the form of biofilms. Once has entered the host and traversed the hostile stomach environment, it must penetrate the mucous layer and adhere to and colonize the epithelial cells of the small intestine. To achieve this, produces a number of virulence factors, including the cholerae toxin (CT) and the toxin coregulated pilus (TCP). TCP is a type IV pilus encoded by the pathogenicity island (VPI) whose probable function is to mediate adherence to the intestinal mucosal cells. When the quorum-sensing pathways of were being dissected at the molecular level, it was noted that the simultaneous mutation of both the CAI-1 and AI-2 systems did not abolish density-dependent light induction from the operon. The mechanisms of quorum-sensing control of biofilm formation in is further complicated by a recent finding that the concentration of the autoinducer CAI-1 is higher in biofilms than in planktonic cultures. To assess the significance of quorum sensing, it is important to carry out experiments under conditions that mimic as closely as possible the natural habitat of .

Citation: Stirling F, Liu Z, Zhu J. 2008. Quorum Sensing in Pathogenesis, p 145-160. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch10

Key Concept Ranking

Gene Expression and Regulation
Quorum Sensing
Furanosyl Borate Diester
Toxin Coregulated Pilus
Signal Transduction
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Image of FIGURE 1

Current model for quorum sensing in At low cell density, LuxQ, CqsA, and LuxU act as autophosphorylating kinases that cause LuxO phosphorylation. Phosphorylated LuxO, in conjunction with σ and Fis, induces the synthesis of the Qrr1–4 sRNAs that act with Hfq to repress HapR production. CsrA also functions via an unknown component (X) to activate LuxO. At high cell density, the autoinducers AI-2 and CAI-1 (produced by LuxS and CqsA, respectively) accumulate and bind to their cognate receptors, LuxP and CqsS. LuxQ, CqsS, and LuxU function as phosphatases, and LuxO is dephosphorylated. Dephosphorylated LuxO is inactive and cannot repress HapR; thus, HapR is produced. CsrA is also repressed by the VarS/VarA/CsrB, C, and D sRNA pathway and thus cannot activate LuxO. VqmA further activates HapR, and HapR functions as an autorepressor. OM, outer membrane; IM, inner membrane; P, phosphate group; gray arrows, direction of phosphate flow; dashed arrows, hypothetical interaction.

Citation: Stirling F, Liu Z, Zhu J. 2008. Quorum Sensing in Pathogenesis, p 145-160. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch10
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Image of FIGURE 2

Repression of virulence factors by HapR. Under conditions that are conducive for virulence factor expression, TcpPH and ToxRS activate the expression of which in turn leads to expression of genes required for the synthesis of cholera toxin and toxin coregulated pili. When HapR is produced at high cell density, it represses the transcription of The repression of AphA leads to the downregulation of TcpPH, ToxT, and subsequently virulence factor expression. TCP, toxin coregulated pili; CT, cholera toxin.

Citation: Stirling F, Liu Z, Zhu J. 2008. Quorum Sensing in Pathogenesis, p 145-160. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch10
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Image of FIGURE 3

Repression of biofilms by HapR. At high cell density, HapR represses polysaccharide expression and therefore biofilm formation. This repression may be via direct repression of the genes, by repression of the positive regulators VpsR or VpsT, or by modulating the level of c-diGMP in the cell. High levels of c-diGMP activate polysaccharide expression, and HapR may function to reduce the c-diGMP concentration in the cell by activating EAL domain containing phosphodiesterases, for example, AcgA, or by repressing GGDEF domain containing diguanylate cyclases, for example, CdgA. The interactions between HapR and the other proteins are not necessarily direct. VPS, polysaccharide.

Citation: Stirling F, Liu Z, Zhu J. 2008. Quorum Sensing in Pathogenesis, p 145-160. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch10
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