ToxR interferes with CRP‐dependent transcriptional activation of <i>ompT</i> in <i>Vibrio cholerae</i>

Li, Caiyi C.; Merrell, D. Scott; Camilli, Andrew; Kaper, James B.

doi:10.1046/j.1365-2958.2002.02845.x

Cited by 38 publications

(42 citation statements)

References 52 publications

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“…OmpT and OmpW have been reported to be strongly induced in rabbit ileal loops (Xu et al, 2003). Downregulation of ompT in the Dcrp mutant is consistent with the report of Li et al (2002) showing that CRP directly activates the ompT promoter. As expected, the Dcrp mutants displayed increased sensitivity to sodium deoxycholate.…”

Section: Discussionsupporting

confidence: 88%

The cyclic AMP receptor protein modulates quorum sensing, motility and multiple genes that affect intestinal colonization in Vibrio cholerae

et al. 2007

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Vibrio cholerae is the causative agent of cholera, which continues to be a major public health concern in Asia, Africa and Latin America. The bacterium can persist outside the human host and alternates between planktonic and biofilm community lifestyles. Transition between the different lifestyles is mediated by multiple signal transduction pathways including quorum sensing. Expression of the Zn-metalloprotease haemagglutinin (HA)/protease is subject to a dual regulation which involves the quorum-sensing regulator HapR and the cAMP receptor protein. In a previous study, we observed that a mutant defective in the cAMP-receptor protein (CRP) expressed lower levels of HapR. To further investigate the role of CRP in modulating HapR and other signal transduction pathways, we performed global gene expression profiling of a Dcrp mutant of El Tor biotype V. cholerae. Here we show that CRP is required for the biosynthesis of cholera autoinducer 1 (CAI-1) and affects the expression of multiple HapR-regulated genes. As expected, the Dcrp mutant produced more cholera toxin and enhanced biofilm. Expression of flagellar genes, reported to be affected in DhapR mutants, was diminished in the Dcrp mutant. However, an epistasis analysis indicated that cAMP-CRP affects motility by a mechanism independent of HapR. Inactivation of crp inhibited the expression of multiple genes reported to be strongly induced in vivo and to affect the ability of V. cholerae to colonize the small intestine and cause disease. These genes included ompU, ompT and ompW encoding outer-membrane proteins, the alternative sigma factor s E required for intestinal colonization, and genes involved in anaerobic energy metabolism. Our results indicate that CRP plays a crucial role in the V. cholerae life cycle by affecting quorum sensing and multiple genes required for survival of V. cholerae in the human host and the environment.

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Section: Discussionsupporting

confidence: 88%

The cyclic AMP receptor protein modulates quorum sensing, motility and multiple genes that affect intestinal colonization in Vibrio cholerae

et al. 2007

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“…The toxTindependent branch includes two outer membrane porins called OmpU and OmpT (9). These two porins are directly and differentially regulated by ToxR in that ompU transcription is induced, whereas ompT transcription is repressed (2,6,9). There are some studies that suggest important functions for ompU during intestinal colonization, namely, increased resistance to bile and anionic detergents (13,14), an organic acid tolerance response (7), and adhesion to epithelial cells (18).…”

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confidence: 99%

The ompU Paralogue vca1008 Is Required for Virulence of Vibrio cholerae

2004

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We made single and combined mutations in ompU, ompT, and the two putative porin genes vca1008 and vc0972. The fitness of the strains was tested in vitro and in the infant mouse model of intestinal infection. We also studied the transcriptional induction of vca1008 in vitro and during mouse infection. We show that vca1008 is induced during infection and is necessary and sufficient (in the absence of ompU, ompT, and vc0972) for infection.Vibrio cholerae is a gram-negative bacterium and facultative pathogen that can cause an acute secretory diarrhea known as cholera. When V. cholerae enters a host it has to sense the new environment and induce an adaptive response that facilitates its survival and multiplication in the small intestine. ToxR is a transmembrane transcriptional activator that is part of a complex virulence gene regulon (the ToxR regulon) of more than 20 genes (9,12,17). The ToxR regulon is organized in two separate branches: the toxT-dependent and the toxT-independent branches. In the toxT-dependent branch, the transcriptional activator ToxT, controlled directly by ToxR, regulates the transcription of the cholera toxin and toxin-coregulated pilus and other factors essential for virulence (3). The toxTindependent branch includes two outer membrane porins called OmpU and OmpT (9). These two porins are directly and differentially regulated by ToxR in that ompU transcription is induced, whereas ompT transcription is repressed (2, 6, 9). There are some studies that suggest important functions for ompU during intestinal colonization, namely, increased resistance to bile and anionic detergents (13,14), an organic acid tolerance response (7), and adhesion to epithelial cells (18). However, one study reported that OmpU does not mediate adherence to rabbit intestinal epithelia (11), and another study reported that ⌬ompU and ⌬ompT strains exhibited no growth defect in vitro nor any detectable attenuation of virulence in infant mice (14).We recently used the recombination-based in vivo expression technology (RIVET) (1) to identify V. cholerae gene vca1008 as being transcriptionally induced during infection of the infant mouse small intestine (C. Osorio, J. Crawford, J. Michalsky, H. Martinez-Wilson, J. Kaper, and A. Camilli, unpublished data). This gene is one of three putative porin genes located on chromosome (Chr) II, and it encodes a protein that is closely related to the Chr I-encoded OmpU porin, having 33% identity and 55% similarity. The other Chr II-encoded putative porins, OmpS and OmpW, are orthologues of the Escherichia coli maltose-specific LamB and uncharacterized OmpW, respectively. The OmpU and VCA1008 paralogues are more closely related to the E. coli nonspecific porins OmpF, OmpC, and PhoE than are the other putative or known porins of V. cholerae (Fig. 1). In contrast, V. cholerae OmpT and VC0972 porins are only distantly related to these proteins (Fig. 1).The relatedness of OmpU and VCA1008 leads to the possibility of an overlap in their function, which might explain why mutations in ompU alone...

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“…cAMP is an important signalling molecule regulating various cellular functions, including virulence factors from a diverse range of pathogens (Alspaugh et al, 2002;Caler et al, 2000;D'Souza & Heitman, 2001;Gross et al, 2003;Lee et al, 2003;Li et al, 2002). There is little information about the role of cAMP in mycobacteria, despite its presence in both fast-and slow-growing, as well as pathogenic and nonpathogenic, species (Padh & Venkitasubramanian, 1977).…”

Section: Discussionmentioning

confidence: 99%

Regulation of the expression of whiB1 in Mycobacterium tuberculosis: role of cAMP receptor protein

2006

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The wbl (whiB-like) genes encode putative transcription factors unique to actinomycetes. This study characterized the promoter element of one of the seven wbl genes of Mycobacterium tuberculosis, whiB1 (Rv3219c). The results reveal that whiB1 is transcribed by a class I-type cAMP receptor protein (CRP)-dependent promoter, harbouring a CRP-binding site positioned at "58?5 with respect to its transcription start point. In vivo promoter activity analysis and electrophoretic mobility shift assays suggest that the expression of whiB1 is indeed regulated by cAMP-dependent binding of CRP M (encoded by the M. tuberculosis gene Rv3676) to the whiB1 59 untranslated region (59UTR). b-Galactosidase gene fusion analysis revealed induction of the whiB1 promoter in M. tuberculosis on addition of exogenous dibutyric cAMP (a diffusible cAMP analogue) only when an intact CRP-binding site was present. These results indicate that M. tuberculosis whiB1 transcription is regulated in part by cAMP levels via direct binding of cAMP-activated CRP M to a consensus CRP-binding site in the whiB1 59UTR. INTRODUCTIONMycobacterium tuberculosis, the aetiological agent of tuberculosis, accounts for nearly 2 million human deaths every year. Approximately one-third of the world's population is latently infected with M. tuberculosis, and 7 to 8 million new TB cases occur annually (Dye et al., 1999). M. tuberculosis can survive in diverse surroundings ranging from the human host to droplet nuclei in the atmosphere. Adaptation to such diverse conditions requires controlled regulation of the expression of key genes that allow the bacillus to alter its physiology in response to changes in environmental stimuli. Sequencing of the M. tuberculosis genome has revealed the presence of more than 100 regulatory proteins, 13 sigma factors and 11 two-component systems (Cole et al., 1998), which provide the bacterium with a high degree of adaptability.The Wbl (WhiB-like) family of proteins is present throughout the actinomycetes but absent from all other organisms evaluated so far (Molle et al., 2000;Soliveri et al., 2000). Due to the presence of a conserved helix-turn-helix motif, these proteins are believed to function as DNA-binding transcription regulators. The first of these proteins, WhiB, was identified in Streptomyces coelicolor, a Gram-positive sporulating bacterium closely related to M. tuberculosis. S. coelicolor whiB mutants produce abnormally long, tightly coiled aerial hyphae that are completely blocked in their ability to form sporulation septa (Chater, 1972;Davis & Chater, 1992;Flardh et al., 1999). Studies of whiB orthologues in mycobacteria have shown that the M. smegmatis whiB2 gene (also called whmD) is essential ; M. tuberculosis whiB3 plays a role in virulence and its gene product may interact with a sigma factor of RNA polymerase (Steyn et al., 2002); whiB7 of M. tuberculosis is involved in multi-drug resistance (Morris et al., 2005). Each of the Wbl family of proteins contains four invariant cysteine residues, which are believed to be inv...

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ToxR interferes with CRP‐dependent transcriptional activation of ompT in Vibrio cholerae

Cited by 38 publications

References 52 publications

The cyclic AMP receptor protein modulates quorum sensing, motility and multiple genes that affect intestinal colonization in Vibrio cholerae

The cyclic AMP receptor protein modulates quorum sensing, motility and multiple genes that affect intestinal colonization in Vibrio cholerae

The ompU Paralogue vca1008 Is Required for Virulence of Vibrio cholerae

Regulation of the expression of whiB1 in Mycobacterium tuberculosis: role of cAMP receptor protein

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