The quorum sensing transcription factor AphA directly regulates natural competence in Vibrio cholerae

Haycocks, James R. J.; Warren, Gemma; Walker, Lucas; Chlebek, Jennifer L.; Dalia, Triana N.; Grainger, David C.

doi:10.1371/journal.pgen.1008362

Cited by 30 publications

(30 citation statements)

References 63 publications

(98 reference statements)

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“…Little is known about vchM regulation but it was recently shown that the V . cholerae quorum sensing low density transcriptional regulator AphA is able to bind the vchM region [ 55 ] leaving the possibility that vchM may be regulated by quorum sensing. Moreover, vchM was previously found to be differentially expressed between different stages of human infection [ 56 ], suggesting the possibility that modulation of cytosine methylation levels can be adaptative during V .…”

Section: Discussionmentioning

confidence: 99%

Deficiency in cytosine DNA methylation leads to high chaperonin expression and tolerance to aminoglycosides in Vibrio cholerae

2021

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Antibiotic resistance has become a major global issue. Understanding the molecular mechanisms underlying microbial adaptation to antibiotics is of keen importance to fight Antimicrobial Resistance (AMR). Aminoglycosides are a class of antibiotics that target the small subunit of the bacterial ribosome, disrupting translational fidelity and increasing the levels of misfolded proteins in the cell. In this work, we investigated the role of VchM, a DNA methyltransferase, in the response of the human pathogen Vibrio cholerae to aminoglycosides. VchM is a V. cholerae specific orphan m5C DNA methyltransferase that generates cytosine methylation at 5’-RCCGGY-3’ motifs. We show that deletion of vchM, although causing a growth defect in absence of stress, allows V. cholerae cells to cope with aminoglycoside stress at both sub-lethal and lethal concentrations of these antibiotics. Through transcriptomic and genetic approaches, we show that groESL-2 (a specific set of chaperonin-encoding genes located on the second chromosome of V. cholerae), are upregulated in cells lacking vchM and are needed for the tolerance of vchM mutant to lethal aminoglycoside treatment, likely by fighting aminoglycoside-induced misfolded proteins. Interestingly, preventing VchM methylation of the four RCCGGY sites located in groESL-2 region, leads to a higher expression of these genes in WT cells, showing that the expression of these chaperonins is modulated in V. cholerae by DNA methylation.

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Section: Discussionmentioning

confidence: 99%

Deficiency in cytosine DNA methylation leads to high chaperonin expression and tolerance to aminoglycosides in Vibrio cholerae

2021

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“…Haycocks et al mapped global binding of the TF AphA, expressed at low cell density, and found that it activated the virulence cascade during colonisation as well as repressing natural competence. The latter is controlled by the TF HapR under high cell density and as such the study identified a mechanism by which V. cholerae directly regulates the marine-to-host lifestyle switch [86].…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 94%

Plastic Circuits: Regulatory Flexibility in Fine Tuning Pathogen Success

O’Boyle

Turner

Roe

et al. 2020

Trends in Microbiology

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Bacteria encode hundreds of conserved transcription factors that are routinely repurposed to regulate horizontally acquired virulence genes in bacterial pathogens.These transcription factors are often nonessential for growth but can be adapted to regulate genes essential for virulence.Global approaches to map DNA-binding proteins reveal details of direct regulatory reactions that occur in vivo and, combined with gene expression studies, can decipher complete transcription factor regulons.Regulatory rewiring occurs not only between species encoding orthologous genes but also within species, creating very personalised circuits of regulation that benefit individual pathogenic lifestyles.

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“…Regarding QS, we observed that genes known to be activated or inhibited by AphA [27,28] in V. cholerae are, respectively, up-and downregulated by TOB in hapR+ strain (Figure 3A), suggesting activation of the AphA low cell density regulon upon TOB treatment. In V. cholerae, the level of AphA protein is known to be negatively controlled by the concerted action of AI-2, CAI-1 and DPO (an autoinducer that is part of a third QS pathway in V. cholerae [29]), with AphA being barely detectable upon the simultaneous presence of these autoinducers [30].…”

Section: Tob Influences Qs Response Of V Cholerae and Interferes With Ai-2 Signaling Of Photorhabdus Luminescensmentioning

confidence: 99%

Interplay between Sublethal Aminoglycosides and Quorum Sensing: Consequences on Survival in V. cholerae

Carvalho

Krin

Korlowski

et al. 2021

Cells

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Antibiotics are well known drugs which, when present above certain concentrations, are able to inhibit the growth of certain bacteria. However, a growing body of evidence shows that even when present at lower doses (subMIC, for sub-minimal inhibitory concentration), unable to inhibit or affect microbial growth, antibiotics work as signaling molecules, affect gene expression and trigger important bacterial stress responses. However, how subMIC antibiotic signaling interplays with other well-known signaling networks in bacteria (and the consequences of such interplay) is not well understood. In this work, through transcriptomic and genetic approaches, we have explored how quorum-sensing (QS) proficiency of V. cholerae affects this pathogen’s response to subMIC doses of the aminoglycoside tobramycin (TOB). We show that the transcriptomic signature of V. cholerae in response to subMIC TOB depends highly on the presence of QS master regulator HapR. In parallel, we show that subMIC doses of TOB are able to negatively interfere with the AI-2/LuxS QS network of V. cholerae, which seems critical for survival to aminoglycoside treatment and TOB-mediated induction of SOS response in this species. This interplay between QS and aminoglycosides suggests that targeting QS signaling may be a strategy to enhance aminoglycoside efficacy in V. cholerae.

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The quorum sensing transcription factor AphA directly regulates natural competence in Vibrio cholerae

Cited by 30 publications

References 63 publications

Deficiency in cytosine DNA methylation leads to high chaperonin expression and tolerance to aminoglycosides in Vibrio cholerae

Deficiency in cytosine DNA methylation leads to high chaperonin expression and tolerance to aminoglycosides in Vibrio cholerae

Plastic Circuits: Regulatory Flexibility in Fine Tuning Pathogen Success

Interplay between Sublethal Aminoglycosides and Quorum Sensing: Consequences on Survival in V. cholerae

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