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Chapter 11 : Signal Integration and Virulence Gene Regulation in

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Abstract:

In addition to the quorum-sensing two-component system (TCS) , three other distinct TCSs are presently known to be involved: , and . This chapter begins with the well-studied locus, ≈3 kb in length and consisting of divergent transcription units, driven by promoters P2 and P3. Indeed, groupings broadly correlate with strain genotypes, and analysis of several strain sets revealed that genotypic class, with rare exceptions, associated with a single group, pointing to group differentiation as a primary evolutionary event that preceded genotypic divergence. The role of was recently analyzed using an antisense RNA approach to repress its expression conditionally, with which it was demonstrated that this TCS differentially regulates virulence genes such as and in aerobic and anaerobic conditions. It has been noted that the pore-forming Panton-Valentine leukocidin toxin, associated with staphylococcal necrotizing pneumonia, has recently also been demonstrated to downregulate the expression of several exoproteins at the transcriptional level, and it is predicted that yet other variable genes encoding toxins that cause toxinoses will be shown to act in the manner described above. Transcription factors feed back to , establishing additional feedback loops, and probably interact similarly with the other TCSs. At least two of the superantigens (SAgs), signaling through BB-4, transmit information through the transcription factors for downregulation of the various exoprotein genes.

Citation: Geisinger E, Novick R. 2008. Signal Integration and Virulence Gene Regulation in , p 161-184. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch11

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Image of FIGURE 1
FIGURE 1

The two-component systems known to affect the virulon. (A) The quorum-sensing system. The pro-AIP peptide is processed and secreted by AgrB, binds to an extracellular loop in the receptor-HPK, AgrC, activating autophosphorylation, followed by phosphorylation of the response regulator, AgrA, which, in conjunction with SarA, activates the two promoters, P2 and P3, leading to the production of RNAIII, which controls transcription of the target genes via intracellular regulatory mediators, including Rot and a second two-component module, and possibly others. (B). . The locus, about 3.5 kb, contains four open reading frames, P, Q, R, and S. R and S form a classical two-component signaling module. The functions of P and Q are unknown. is transcribed from two or three promoters, one of which is active in an -null strain and the other(s) is activated by RNAIII. All three major transcripts, A, B, and C, end at ter. D may be independently transcribed or derived from C by processing. PCR probes used to map the transcripts are shown. (C). (adapted from Fournier et al. [ ]). The locus encodes a receptor-HPK () and a response regulator (), driven by a single promoter and followed by a terminator stem-loop. (D). (adapted from Yarwood et al. [ ]). The locus encodes a receptor-HPK () and a response regulator (), driven by a single promoter that generates two transcripts whose relative significance is unknown.

Citation: Geisinger E, Novick R. 2008. Signal Integration and Virulence Gene Regulation in , p 161-184. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch11
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Image of FIGURE 2
FIGURE 2

Comparison of sequences. Sequences were aligned visually. Predicted AIPs are in bold and are set between spaces. Those for which sequence has been confirmed by in vitro synthesis or by mass spectroscopy are indicated with footnote. Saur, ; Sarc, ; Sarl, ; Scap, ; Scapr, ; Scarn, ; Sconc, ; Sconu, ; Sepi, ; Sgal, ; Sint, ; Slug, ; Ssim, ;Swar, ; Sxyl, .

Citation: Geisinger E, Novick R. 2008. Signal Integration and Virulence Gene Regulation in , p 161-184. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch11
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Image of FIGURE 3
FIGURE 3

Regulatory interactions involving SarA and its homologs. Arrows represent upregulation, bars represent downregulation. Gray lines represent translation; black lines represent interactions that are probably, but not always certainly, transcriptional. The interactions illustrated are based on reviews by Arvidson and Tegmark ( ) and Cheung and Zhang ( ) and on papers by Manna and Cheung ( ), Ingavale et al. ( ), and Said-Salim et al. ( ). Although the abbreviations are mostly in italics, on the assumption that the interactions are likely to be at the transcriptional level, there is actually very little evidence to indicate whether they are direct or indirect or at what level they occur. Question marks represent the most speculative. σ is shown entering the system via and , which have σ-dependent promoters and are likely to represent important intermediates in the pathways by which environmental signals are handled.

Citation: Geisinger E, Novick R. 2008. Signal Integration and Virulence Gene Regulation in , p 161-184. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch11
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Tables

Generic image for table
TABLE 1

Staphylococcal extracellular accessory proteins

Citation: Geisinger E, Novick R. 2008. Signal Integration and Virulence Gene Regulation in , p 161-184. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch11
Generic image for table
TABLE 2

Known accessory gene regulation and transcription units in

Citation: Geisinger E, Novick R. 2008. Signal Integration and Virulence Gene Regulation in , p 161-184. In Winans S, Bassler B (ed), Chemical Communication among Bacteria. ASM Press, Washington, DC. doi: 10.1128/9781555815578.ch11

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