scholarly journals A new class of inhibitors of the AraC family virulence regulator Vibrio cholerae ToxT

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Anne K. Woodbrey ◽  
Evans O. Onyango ◽  
Maria Pellegrini ◽  
Gabriela Kovacikova ◽  
Ronald K. Taylor ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
New Class ◽  
Virulence Regulator ◽  
Arac Family

scholarly journals Cyclo(valine–valine) inhibits Vibrio cholerae virulence gene expression

Microbiology ◽  
2014 ◽  
Vol 160 (6) ◽  
pp. 1054-1062 ◽  
Author(s):  
Amit Vikram ◽  
Vanessa M. Ante ◽  
X. Renee Bina ◽  
Qin Zhu ◽  
Xinyu Liu ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
Virulence Factor ◽  
Inhibitory Activity ◽  
Virulence Gene ◽  
Side Chains ◽  
Cyclic Dipeptides ◽  
Virulence Gene Expression ◽  
Factor Production ◽  
Virulence Regulator ◽  
Virulence Factor Production

Vibrio cholerae has been shown to produce a cyclic dipeptide, cyclo(phenylalanine–proline) (cFP), that functions to repress virulence factor production. The objective of this study was to determine if heterologous cyclic dipeptides could repress V. cholerae virulence factor production. To that end, three synthetic cyclic dipeptides that differed in their side chains from cFP were assayed for virulence inhibitory activity in V. cholerae. The results revealed that cyclo(valine–valine) (cVV) inhibited virulence factor production by a ToxR-dependent process that resulted in the repression of the virulence regulator aphA. cVV-dependent repression of aphA was found to be independent of known aphA regulatory genes. The results demonstrated that V. cholerae was able to respond to exogenous cyclic dipeptides and implicated the hydrophobic amino acid side chains on both arms of the cyclo dipeptide scaffold as structural requirements for inhibitory activity. The results further suggest that cyclic dipeptides have potential as therapeutics for cholera treatment.

scholarly journals Structure and Function of the Vibrio cholerae Master Virulence Regulator ToxT

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Justin Cruite ◽  
Gabriela Kovacikova ◽  
Karen Skorupski ◽  
Ronald Taylor ◽  
F. Jon Kull
Keyword(s):  
Vibrio Cholerae ◽  
Structure And Function ◽  
And Function ◽  
Virulence Regulator

scholarly journals Binding Site Recognition by Rns, a Virulence Regulator in the AraC Family

1999 ◽  
Vol 181 (7) ◽  
pp. 2110-2117 ◽  
Author(s):  
George P. Munson ◽  
June R. Scott
Keyword(s):  
Binding Sites ◽  
Shigella Flexneri ◽  
Transcriptional Level ◽  
Regulatory Cascade ◽  
Dnase I Footprinting ◽  
Nucleotide Interactions ◽  
Virulence Regulator ◽  
Arac Family

ABSTRACT The expression of CS1 pili by enterotoxigenic strains ofEscherichia coli is regulated at the transcriptional level and requires the virulence regulator Rns, a member of the AraC family of regulatory proteins. Rns binds at two separate sites upstream of Pcoo (the promoter of CS1 pilin genes), which were identified in vitro with an MBP::Rns fusion protein in gel mobility and DNase I footprinting assays. At each site, Rns recognizes asymmetric nucleotide sequences in two regions of the major groove and binds along one face of the DNA helix. Both binding sites are required for activation of Pcoo in vivo, because mutagenesis of either site significantly reduced the level of expression from this promoter. Thus, Rns regulates the expression of CS1 pilin genes directly, not via a regulatory cascade. Analysis of Rns-nucleotide interactions at each site suggests that binding sites for Rns and related virulence regulators are not easily identified because they do not bind palindromic or repeated sequences. A strategy to identify asymmetric binding sites is presented and applied to locate potential binding sites upstream of other genes that Rns can activate, including those encoding the CS2 and CFA/I pili of enterotoxigenic E. coli and the global regulator virB of Shigella flexneri.

Identification and Characterization of a New Class of (6–4) Photolyase from Vibrio cholerae

Biochemistry ◽  
2019 ◽  
Vol 58 (43) ◽  
pp. 4352-4360 ◽  
Author(s):  
Ugur Meric Dikbas ◽  
Mehmet Tardu ◽  
Asena Canturk ◽  
Seref Gul ◽  
Gozde Ozcelik ◽  
...  
Keyword(s):  
Vibrio Cholerae ◽  
New Class ◽  
Identification And Characterization

scholarly journals Calcium Enhances Bile Salt-Dependent Virulence Activation in Vibrio cholerae

2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Amanda J. Hay ◽  
Menghua Yang ◽  
Xiaoyun Xia ◽  
Zhi Liu ◽  
Justin Hammons ◽  
...  
Keyword(s):  
Bile Salt ◽  
Vibrio Cholerae ◽  
Bile Salts ◽  
Diarrheal Disease ◽  
Content Type ◽  
Inner Membrane Protein ◽  
Virulence Regulator ◽  
Host Signals

ABSTRACT Vibrio cholerae is the causative bacteria of the diarrheal disease cholera, but it also persists in aquatic environments, where it displays an expression profile that is distinct from that during infection. Upon entry into the host, a tightly regulated circuit coordinates the induction of two major virulence factors: cholera toxin and a toxin-coregulated pilus (TCP). It has been shown that a set of bile salts, including taurocholate, serve as host signals to activate V. cholerae virulence through inducing the activity of the transmembrane virulence regulator TcpP. In this study, we investigated the role of calcium, an abundant mental ion in the gut, in the regulation of virulence. We show that whereas Ca2+ alone does not affect virulence, Ca2+ enhances bile salt-dependent virulence activation for V. cholerae. The induction of TCP by murine intestinal contents is counteracted when Ca2+ is depleted by the high-affinity calcium chelator EGTA, suggesting that the calcium present in the gut is a relevant signal for V. cholerae virulence induction in vivo. We further show that Ca2+ enhances virulence by promoting bile salt-induced TcpP-TcpP interaction. Moreover, fluorescence recovery after photobleaching (FRAP) analysis demonstrated that exposure to bile salts and Ca2+ together decreases the recovery rate for fluorescently labeled TcpP, but not for another inner membrane protein (TatA). Together, these data support a model in which physiological levels of Ca2+ may result in altered bile salt-induced TcpP protein movement and activity, ultimately leading to an increased expression of virulence.

scholarly journals The Fatty Acid Regulator FadR Influences the Expression of the Virulence Cascade in the El Tor Biotype of Vibrio cholerae by Modulating the Levels of ToxT via Two Different Mechanisms

2017 ◽  
Vol 199 (7) ◽  
Author(s):  
Gabriela Kovacikova ◽  
Wei Lin ◽  
Ronald K. Taylor ◽  
Karen Skorupski
Keyword(s):  
Gene Expression ◽  
Vibrio Cholerae ◽  
Virulence Gene ◽  
Enteric Bacteria ◽  
Posttranslational Regulation ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Expression Of Genes ◽  
El Tor ◽  
Virulence Regulator

ABSTRACT FadR is a master regulator of fatty acid (FA) metabolism that coordinates the pathways of FA degradation and biosynthesis in enteric bacteria. We show here that a ΔfadR mutation in the El Tor biotype of Vibrio cholerae prevents the expression of the virulence cascade by influencing both the transcription and the posttranslational regulation of the master virulence regulator ToxT. FadR is a transcriptional regulator that represses the expression of genes involved in FA degradation, activates the expression of genes involved in unsaturated FA (UFA) biosynthesis, and also activates the expression of two operons involved in saturated FA (SFA) biosynthesis. Since FadR does not bind directly to the toxT promoter, we determined whether the regulation of any of its target genes indirectly influenced ToxT. This was accomplished by individually inserting a double point mutation into the FadR-binding site in the promoter of each target gene, thereby preventing their activation or repression. Although preventing FadR-mediated activation of fabA, which encodes the enzyme that carries out the first step in UFA biosynthesis, did not significantly influence either the transcription or the translation of ToxT, it reduced its levels and prevented virulence gene expression. In the mutant strain unable to carry out FadR-mediated activation of fabA, expressing fabA ectopically restored the levels of ToxT and virulence gene expression. Taken together, the results presented here indicate that V. cholerae FadR influences the virulence cascade in the El Tor biotype by modulating the levels of ToxT via two different mechanisms. IMPORTANCE Fatty acids (FAs) play important roles in membrane lipid homeostasis and energy metabolism in all organisms. In Vibrio cholerae, the causative agent of the acute intestinal disease cholera, they also influence virulence by binding into an N-terminal pocket of the master virulence regulator, ToxT, and modulating its activity. FadR is a transcription factor that coordinately controls the pathways of FA degradation and biosynthesis in enteric bacteria. This study identifies a new link between FA metabolism and virulence in the El Tor biotype by showing that FadR influences both the transcription and posttranslational regulation of the master virulence regulator ToxT by two distinct mechanisms.

scholarly journals Vibrio cholerae virulence regulator-coordinated evasion of host immunity

2006 ◽  
Vol 103 (39) ◽  
pp. 14542-14547 ◽  
Author(s):  
A. Hsiao ◽  
Z. Liu ◽  
A. Joelsson ◽  
J. Zhu
Keyword(s):  
Vibrio Cholerae ◽  
Host Immunity ◽  
Virulence Regulator
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