The VarS/VarA Two-component System Modulates the Activity of the Vibrio Cholerae Quorum-sensing Transcriptional Regulator HapR

Overview

Journal Microbiology (Reading)

Specialty Microbiology

Date 2011 Mar 12

PMID 21393367

Citations 36

Authors

Amy M Tsou

Zhi Liu

Tao Cai

Jun Zhu

Affiliations

Soon will be listed here.

Abstract

The human pathogen Vibrio cholerae uses quorum sensing to regulate the expression of a number of phenotypes, including virulence factor production, in response to changes in cell density. It produces small molecules called autoinducers that increase in concentration as cell density increases, and these autoinducers bind to membrane sensors once they reach a certain threshold. This binding leads to signalling through a downstream phosphorelay pathway to alter the expression of the transcriptional regulator HapR. Previously, it was shown that the VarS/VarA two-component system acts on a component of the phosphorelay pathway upstream of HapR to regulate HapR expression levels. Here, we show that in addition to this mechanism of regulation, VarS and VarA also indirectly modulate HapR protein activity. This modulation is mediated by the small RNA CsrB but is independent of the known quorum-sensing system that links the autoinducers to HapR. Thus, the VarS/VarA two-component system intersects with the quorum-sensing network at two levels. In both cases, the effect of VarS and VarA on quorum sensing is dependent on the Csr small RNAs, which regulate carbon metabolism, suggesting that V. cholerae may integrate nutrient status and cell density sensory inputs to tailor its gene expression profile more precisely to surrounding conditions.

Citing Articles

The activity of the quorum sensing regulator HapR is modulated by the bacterial extracellular vesicle (BEV)-associated protein ObfA of Vibrio cholerae.

Ebenberger S, Cakar F, Chen Y, Pressler K, Eberl L, Schild S J Extracell Vesicles. 2024; 13(9):e12507.

PMID: 39252550 PMC: 11386269. DOI: 10.1002/jev2.12507.

Reprogramming of phytopathogen transcriptome by a non-bactericidal pesticide residue alleviates its virulence in rice.

Matsumoto H, Qian Y, Fan X, Chen S, Nie Y, Qiao K Fundam Res. 2024; 2(2):198-207.

PMID: 38933150 PMC: 11197535. DOI: 10.1016/j.fmre.2021.12.012.

L-arabinose affects the growth, biofilm formation, motility, c-di-GMP metabolism, and global gene expression of .

Zhang M, Luo X, Li X, Zhang T, Wu F, Li M J Bacteriol. 2023; 205(9):e0010023.

PMID: 37655915 PMC: 10521368. DOI: 10.1128/jb.00100-23.

Quorum sensing and QsvR tightly control the transcription of encoding an active RNase II-type protein in .

Zhang Y, Xue X, Sun F, Li X, Zhang M, Wu Q Front Microbiol. 2023; 14:1123524.

PMID: 36744098 PMC: 9894610. DOI: 10.3389/fmicb.2023.1123524.

Heterologous expression of quorum sensing transcriptional regulator LitR and its function in virulence-related gene regulation in foodborne pathogen Aeromonas hydrophila.

Zhao J, Li Y, Huang Y, Jin L, Xu Y, Xu M Mol Biol Rep. 2022; 50(3):2049-2060.

PMID: 36542235 DOI: 10.1007/s11033-022-07866-4.

References

Liu Z, Miyashiro T, Tsou A, Hsiao A, Goulian M, Zhu J . Mucosal penetration primes Vibrio cholerae for host colonization by repressing quorum sensing. Proc Natl Acad Sci U S A. 2008; 105(28):9769-74. PMC: 2474479. DOI: 10.1073/pnas.0802241105. View

Sabnis N, Yang H, Romeo T . Pleiotropic regulation of central carbohydrate metabolism in Escherichia coli via the gene csrA. J Biol Chem. 1995; 270(49):29096-104. DOI: 10.1074/jbc.270.49.29096. View

Weilbacher T, Suzuki K, Dubey A, Wang X, Gudapaty S, Morozov I . A novel sRNA component of the carbon storage regulatory system of Escherichia coli. Mol Microbiol. 2003; 48(3):657-70. DOI: 10.1046/j.1365-2958.2003.03459.x. View

De Silva R, Kovacikova G, Lin W, Taylor R, Skorupski K, Kull F . Crystal structure of the Vibrio cholerae quorum-sensing regulatory protein HapR. J Bacteriol. 2007; 189(15):5683-91. PMC: 1951804. DOI: 10.1128/JB.01807-06. View

Hammer B, Bassler B . Quorum sensing controls biofilm formation in Vibrio cholerae. Mol Microbiol. 2003; 50(1):101-4. DOI: 10.1046/j.1365-2958.2003.03688.x. View

Tsou A, Cai T, Liu Z, Zhu J, Kulkarni R . Regulatory targets of quorum sensing in Vibrio cholerae: evidence for two distinct HapR-binding motifs. Nucleic Acids Res. 2009; 37(8):2747-56. PMC: 2677876. DOI: 10.1093/nar/gkp121. View

Herren C, Mitra A, Palaniyandi S, Coleman A, Elankumaran S, Mukhopadhyay S . The BarA-UvrY two-component system regulates virulence in avian pathogenic Escherichia coli O78:K80:H9. Infect Immun. 2006; 74(8):4900-9. PMC: 1539585. DOI: 10.1128/IAI.00412-06. View

Liu M, Gui G, Wei B, Preston 3rd J, Oakford L, Yuksel U . The RNA molecule CsrB binds to the global regulatory protein CsrA and antagonizes its activity in Escherichia coli. J Biol Chem. 1997; 272(28):17502-10. DOI: 10.1074/jbc.272.28.17502. View

Wong S, Carroll P, Rahme L, Ausubel F, Calderwood S . Modulation of expression of the ToxR regulon in Vibrio cholerae by a member of the two-component family of response regulators. Infect Immun. 1998; 66(12):5854-61. PMC: 108741. DOI: 10.1128/IAI.66.12.5854-5861.1998. View

10.

Metcalf W, Jiang W, Daniels L, Kim S, Haldimann A, Wanner B . Conditionally replicative and conjugative plasmids carrying lacZ alpha for cloning, mutagenesis, and allele replacement in bacteria. Plasmid. 1996; 35(1):1-13. DOI: 10.1006/plas.1996.0001. View

11.

Romeo T, Gong M, Liu M, Brun-Zinkernagel A . Identification and molecular characterization of csrA, a pleiotropic gene from Escherichia coli that affects glycogen biosynthesis, gluconeogenesis, cell size, and surface properties. J Bacteriol. 1993; 175(15):4744-55. PMC: 204926. DOI: 10.1128/jb.175.15.4744-4755.1993. View

12.

Pernestig A, Georgellis D, Romeo T, Suzuki K, Tomenius H, Normark S . The Escherichia coli BarA-UvrY two-component system is needed for efficient switching between glycolytic and gluconeogenic carbon sources. J Bacteriol. 2003; 185(3):843-53. PMC: 142795. DOI: 10.1128/JB.185.3.843-853.2003. View

13.

Neiditch M, Federle M, Pompeani A, Kelly R, Swem D, Jeffrey P . Ligand-induced asymmetry in histidine sensor kinase complex regulates quorum sensing. Cell. 2006; 126(6):1095-108. PMC: 3468944. DOI: 10.1016/j.cell.2006.07.032. View

14.

Gao R, Mack T, Stock A . Bacterial response regulators: versatile regulatory strategies from common domains. Trends Biochem Sci. 2007; 32(5):225-34. PMC: 3655528. DOI: 10.1016/j.tibs.2007.03.002. View

15.

Hsiao A, Liu Z, Joelsson A, Zhu J . Vibrio cholerae virulence regulator-coordinated evasion of host immunity. Proc Natl Acad Sci U S A. 2006; 103(39):14542-7. PMC: 1599996. DOI: 10.1073/pnas.0604650103. View

16.

Liu Z, Hsiao A, Joelsson A, Zhu J . The transcriptional regulator VqmA increases expression of the quorum-sensing activator HapR in Vibrio cholerae. J Bacteriol. 2006; 188(7):2446-53. PMC: 1428415. DOI: 10.1128/JB.188.7.2446-2453.2006. View

17.

Zhu J, Mekalanos J . Quorum sensing-dependent biofilms enhance colonization in Vibrio cholerae. Dev Cell. 2003; 5(4):647-56. DOI: 10.1016/s1534-5807(03)00295-8. View

18.

Mitrophanov A, Groisman E . Signal integration in bacterial two-component regulatory systems. Genes Dev. 2008; 22(19):2601-11. PMC: 2751022. DOI: 10.1101/gad.1700308. View

19.

Miller M, Skorupski K, Lenz D, Taylor R, Bassler B . Parallel quorum sensing systems converge to regulate virulence in Vibrio cholerae. Cell. 2002; 110(3):303-14. DOI: 10.1016/s0092-8674(02)00829-2. View

20.

Zhu J, Miller M, Vance R, Dziejman M, Bassler B, Mekalanos J . Quorum-sensing regulators control virulence gene expression in Vibrio cholerae. Proc Natl Acad Sci U S A. 2002; 99(5):3129-34. PMC: 122484. DOI: 10.1073/pnas.052694299. View