A Functional
            <i>cra</i>
            Gene Is Required for
            <i>Salmonella enterica</i>
            Serovar Typhimurium Virulence in BALB/c Mice

Allen, James H.; Utley, Maryjane; Bosch, Han van den; Nuijten, Piet J. M.; Witvliet, M.; McCormick, Beth A.; Krogfelt, Karen A.; Licht, Tine Rask; Brown, D. J. F.; Mauel, Michael J.; Leatham, Mary P.; Laux, David C.; Cohen, Paul S.

doi:10.1128/iai.68.6.3772-3775.2000

Cited by 22 publications

(12 citation statements)

References 21 publications

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“…The Cra protein was initially characterized as the fructose repressor FruR and was demonstrated to be a global regulatory protein in carbohydrate metabolism (Saier & Ramseier, 1996). Although it has been shown that Cra regulates numerous genes involved in carbohydrate metabolism (Saier & Ramseier, 1996; Sarkar et al , 2008), growth rate (Ow et al , 2007) and bacterial virulence (Allen et al , 2000), there is no report showing the role of Cra in acid survival. And here, we also detected the decreased expression of cra at acidic pH (Fig.…”

Section: Discussionmentioning

confidence: 99%

Cra negatively regulates acid survival in Yersinia pseudotuberculosis

Zhang

et al. 2011

FEMS Microbiology Letters

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Survival in acidic environments is important for successful infection of gastrointestinal pathogens. Many bacteria have evolved elaborate mechanisms by inducing or repressing gene expression, which subsequently provide pH homeostasis and enable acid survival. In this study, we employed comparative proteomic analysis to identify the acid-responsive proteins of a food-borne enteric bacterium, Yersinia pseudotuberculosis. The expression level of eight proteins involved in carbohydrate metabolism was up- or downregulated over twofold at pH 4.5 compared with pH 7.0. The role of a global transcriptional regulator catabolite repressor/activator Cra was further studied in this acid survival process. lacZ-fusion analysis showed that expression of cra was repressed under acidic pH. Deletion of the cra gene increased acid survival by 10-fold, whereas complementation restored the wild-type phenotype. These results lead us to propose that, in response to acidic pH, the expression of cra gene is downregulated to increase acid survival. This is the first study to demonstrate the regulatory role of Cra in acid survival in an enteric bacterium.

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Section: Discussionmentioning

confidence: 99%

Cra negatively regulates acid survival in Yersinia pseudotuberculosis

Zhang

et al. 2011

FEMS Microbiology Letters

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“…Cra has been reported to be an activator of virulence in both Salmonella (22) and EHEC (34). We previously reported on Cra's ability to activate Ler, the master regulator of the LEE genes, and consequently the transcription and translation of genes in this PI (34).…”

Section: Resultsmentioning

confidence: 99%

“…Due to the fact that Cra and KdpE not only regulate virulence factors (22,23,34) but also are involved in carbon metabolism regulation (15)(16)(17)44), we investigated whether these regulators affected EHEC growth rates. In particular, we wanted to examine differences during growth in low-glucose DMEM, conditions that have been shown to be optimal for LEE gene expression and AE lesion formation in vitro (45,46).…”

Section: Resultsmentioning

confidence: 99%

“…These metabolic intermediates bind to the inducer binding domain of Cra, decreasing its binding affinity for target promoters and consequently decreasing its regulatory function. Cra has been shown to regulate virulence in Salmonella enterica, with the cra mutant being avirulent in murine infections (22)(23)(24), and to be a facilitator of Shigella flexneri pathogenesis (25).…”

mentioning

confidence: 99%

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The Interacting Cra and KdpE Regulators Are Involved in the Expression of Multiple Virulence Factors in Enterohemorrhagic Escherichia coli

2013

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The human pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7 codes for two interacting DNA binding proteins, Cra and KdpE, that coregulate expression of the locus of enterocyte effacement (LEE) genes in a metabolite-dependent manner. Cra is a transcription factor that uses fluctuations in the concentration of carbon metabolism intermediates to positively regulate virulence of EHEC. KdpE is a response regulator that activates the transcription of homeostasis genes in response to salt-induced osmolarity and virulence genes in response to changes in metabolite concentrations. Here, we probed the transcriptional profiles of the ⌬cra, ⌬kdpE, and ⌬cra ⌬kdpE mutant strains and show that Cra and KdpE share several targets besides the LEE, but both Cra and KdpE also have independent targets. Several genes within O-islands (genomic islands present in EHEC but absent from E. coli K-12), such as Z0639, Z0640, Z3388, Z4267, and espFu (encoding an effector necessary for formation of attaching and effacing lesions on epithelial cells), were directly regulated by both Cra and KdpE, while Z2077 was only regulated by Cra. These studies identified and confirmed new direct targets for Cra and KdpE that included putative virulence factors as well as characterized virulence factors, such as EspFu and EspG. These results map out the role of the two interacting regulators, Cra and KdpE, in EHEC pathogenesis and global gene regulation.

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“…Catabolism of C2 substrates such as fatty acids also appears to play a role in Salmonella metabolism in vivo , because mutants of S. typhimurium that cannot grow on C2 substrates in vitro are attenuated in mice (Utley et al ., 1998). Moreover, gene products required for normal growth and/or persistence in vivo include malic enzyme (Valentine et al ., 1998), isocitrate lyase (Fang et al ., 2005) and catabolite repressor/activator (Cra) (Allen et al ., 2000), which upregulates expression of key enzymes in the glyoxylate and gluconeogenesis pathways (Saier and Ramseier, 1996) (Figs 1 and 3). Interestingly, isocitrate lyase appears to be dispensable for acute lethal infection in genetically susceptible mice but essential for persistence in a mouse model of chronic infection (Fang et al ., 2005).…”

Section: Salmonellaementioning

confidence: 99%