Stationary‐phase induction of <scp><i>vvpS</i></scp> expression by three transcription factors: repression by <scp>LeuO</scp> and activation by <scp>SmcR</scp> and <scp>CRP</scp>

Kim, Jeong‐A; Park, Jin Hwan; Lee, Mi-Ae; Lee, Hyunjung; Park, Soon‐Jung; Kim, Kun-Soo; Choi, Sang Ho; Lee, Kyu‐Ho

doi:10.1111/mmi.13028

Cited by 13 publications

(19 citation statements)

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“…In Vibrio parahaemolyticus LeuO has been shown to regulate expression of the type III secretion system, and serine protease production in Vibrio vulnificus (Kim et al, 2015;Whitaker et al, 2012). Taken together these results suggest that LeuO probably functions to regulate diverse genes involved in environmental adaptation in the Vibrionaceae.…”

Section: Discussionmentioning

confidence: 51%

The LysR-type regulator LeuO regulates the acid tolerance response in Vibrio cholerae

Ante

Bina

2015

Microbiology

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Vibrio cholerae is a neutrophilic enteric pathogen that is extremely sensitive to acid. As V. cholerae passages through the host gastrointestinal tract it is exposed to a variety of environmental stresses including low pH and volatile fatty acids. Exposure to acidic environments induces expression of the V. cholerae acid tolerance response. A key component of the acid tolerance response is the cad system, which is encoded by cadC and the cadBA operon. CadB is a lysine/cadaverine antiporter and CadA is a lysine decarboxylase and these function together to counter low intracellular and extracellular pH. CadC is a membrane-associated transcription factor that activates cadBA expression in response to acidic conditions. Herein we investigated the role of the LysR-type transcriptional regulator LeuO in the V. cholerae acid tolerance response. Transcriptional reporter assays revealed that leuO expression repressed cadC transcription, indicating that LeuO was a cadC repressor. Consistent with this, leuO expression was inversely linked to lysine decarboxylase production and leuO overexpression resulted in increased sensitivity to organic acids. Overexpression of leuO in a cadA mutant potentiated killing by organic acids, suggesting that the function of leuO in the acid tolerance response extended beyond its regulation of the cad system. Collectively, these studies have identified a new physiological role for LeuO in V. cholerae acid tolerance.

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Section: Discussionmentioning

confidence: 51%

The LysR-type regulator LeuO regulates the acid tolerance response in Vibrio cholerae

Ante

Bina

2015

Microbiology

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“…LeuO has also been associated with virulence gene regulation in Yersinia enterocolitica (27). The function of LeuO as a global regulator appears to be conserved in the Vibrionaceae, in which LeuO has been shown to contribute to biofilm production, cell wall degradation, and virulence gene regulation (23,(28)(29)(30).…”

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confidence: 99%

Vibrio cholerae leuO Transcription Is Positively Regulated by ToxR and Contributes to Bile Resistance

et al. 2015

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Vibrio cholerae is an aquatic organism and facultative human pathogen that colonizes the small intestine. In the small intestine, V. cholerae is exposed to a variety of antimicrobial compounds, including bile. V. cholerae resistance to bile is multifactorial and includes alterations in the membrane permeability barrier that are mediated by ToxR, a membrane-associated transcription factor. ToxR has also been shown to be required for activation of the LysR family transcription factor leuO in response to cyclic dipeptides. LeuO has been implicated in the regulation of multiple V. cholerae phenotypes, including biofilm production and virulence. In this study, we investigated the effects of bile on leuO expression. We show that leuO transcription increased in response to bile and bile salts but not in response to other detergents. The bile-dependent increase in leuO expression was dependent on ToxR, which was found to bind directly to the leuO promoter. The periplasmic domain of ToxR was required for basal leuO expression and for the bile-dependent induction of both leuO and ompU transcription. V. cholerae mutants that did not express leuO exhibited increased bile susceptibility, suggesting that LeuO contributes to bile resistance. Our collective results demonstrate that ToxR activates leuO expression in response to bile and that LeuO is a component of the ToxR-dependent responses that contribute to bile resistance. IMPORTANCEThe success of Vibrio cholerae as a human pathogen is dependent upon its ability to rapidly adapt to changes in its growth environment. Growth in the human gastrointestinal tract requires the expression of genes that provide resistance to host antimicrobial compounds, including bile. In this work, we show for the first time that the LysR family regulator LeuO mediates responses in V. cholerae that contribute to bile resistance. Vibrio cholerae is a Gram-negative bacterial pathogen and the causal agent of the severe diarrheal disease cholera. V. cholerae exists naturally in aquatic reservoirs and is capable of colonizing the human small intestine. The transition of V. cholerae from the aquatic ecosystem to growth in the human gastrointestinal tract is mediated by transcriptional responses that are required for colonization and disease development. Many of the genes that contribute to intestinal colonization are under the control of the membrane-associated regulatory protein ToxR, which functions as one of the primary regulators in the ToxR regulon (reviewed in reference 1). The ToxR regulon is divided into two branches, a ToxTdependent branch, which controls the expression of virulence factors, and a ToxT-independent branch, which reciprocally regulates the production of the outer membrane porins OmpU and OmpT. The ToxT-dependent branch of the ToxR regulon is a hierarchical regulatory cascade that regulates the expression of genes encoding the production of cholera toxin (CT) and the toxin-coregulated pilus (TCP) in response to environmental cues in the host.ToxR is a membrane-associated ...

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“…Effect of a crp mutation on vvpM transcription. Expression of genes vvpE and vvpS is coactivated by the cAMP-CRP complex via synergistic interactions with SmcR (9,15). To determine whether CRP also participates in vvpM expression, luciferase activity of the vvpM-luxAB transcriptional fusion was monitored in a Δcrp mutant strain.…”

Section: Resultsmentioning

confidence: 99%

“…Expression of both vvpE and vvpS is reported to be induced by the quorum-sensing (QS) regulatory mechanism (9,10). QS functions in a cell density-dependent manner via chemical communication using signaling molecules called autoinducers (AI).…”

mentioning

confidence: 99%

“…In the case of vvpE and vvpS, their expression is activated by direct binding of SmcR to the regulatory regions of the corresponding genes, resulting in production of these exoproteases at high cell density (12,15). A global regulator, cAMP receptor protein (CRP), is also involved in transcription activation of vvpE and vvpS via formation of a complex with 3=,5=-AMP (termed the cAMP-CRP complex) (9,15). The vvpE and vvpS genes have served as experimental models in studies on the molecular mechanisms of transcription regulation coordinately controlled by SmcR with other transcription factors, such as the cAMP-CRP complex, sigma factor S, IHF, Fur, and LeuO (9,16,17).…”

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confidence: 99%

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Repression of VvpM Protease Expression by Quorum Sensing and the cAMP-cAMP Receptor Protein Complex in Vibrio vulnificus

et al. 2018

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Septicemia-causing produces at least three exoproteases, VvpE, VvpS, and VvpM, all of which participate in interactions with human cells. Expression of VvpE and VvpS is induced in the stationary phase by multiple transcription factors, including sigma factor S, SmcR, and the cAMP-cAMP receptor protein (cAMP-CRP) complex. Distinct roles of VvpM, such as induction of apoptosis, lead us to hypothesize VvpM expression is different from that of the other exoproteases. Its transcription, which was found to be independent of sigma S, is induced at the early exponential phase and then becomes negligible upon entry into the stationary phase. SmcR and CRP were studied regarding the control of expression. Transcription of was repressed by SmcR and cAMP-CRP complex individually, which specifically bound to the regions -2 to +20 and +6 to +27, respectively, relative to the transcription initiation site. Derepression of gene expression was 10- to 40-fold greater in an double mutant than in single-gene mutants. Therefore, these results show that the expression of exoproteases is differentially regulated, and in this way, distinct proteases can engage in specific interactions with a host. An opportunistic human pathogen, produces multiple extracellular proteases that are involved in diverse interactions with a host. The total exoproteolytic activity is detected mainly in the supernatants of the high-cell-density cultures. However, some proteolytic activity derived from a metalloprotease, VvpM, was present in the supernatants of the low-cell-density cultures sampled at the early growth period. In this study, we present the regulatory mechanism for VvpM expression via repression by at least two transcription factors. This type of transcriptional regulation is the exact opposite of those for expression of the other exoproteases. Differential regulation of each exoprotease's production then facilitates the pathogen's participation in the distinct interactions with a host.

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Stationary‐phase induction of vvpS expression by three transcription factors: repression by LeuO and activation by SmcR and CRP

Cited by 13 publications

References 57 publications

The LysR-type regulator LeuO regulates the acid tolerance response in Vibrio cholerae

The LysR-type regulator LeuO regulates the acid tolerance response in Vibrio cholerae

Vibrio cholerae leuO Transcription Is Positively Regulated by ToxR and Contributes to Bile Resistance

Repression of VvpM Protease Expression by Quorum Sensing and the cAMP-cAMP Receptor Protein Complex in Vibrio vulnificus

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