l-Cysteine is required for induced antibiotic resistance in actively swarming Salmonella enterica serovar Typhimurium

Turnbull, Amy L.; Surette, Michael G.

doi:10.1099/mic.0.2008/020347-0

Cited by 71 publications

(71 citation statements)

References 40 publications

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“…It has been previously shown that cysteine synthesis is required for antibiotic resistance of swarming cells (60). Therefore, we examined the effect of cysteine catabolism on antibiotic resistance.…”

Section: Resultsmentioning

confidence: 99%

“…Swarming is a form of motility on semisolid surfaces (34). Cysteine auxotrophs do not swarm on a lowcysteine-containing medium, but additional exogenous cysteine restores swarming (30,48,60).…”

Section: Resultsmentioning

confidence: 99%

“…5C). As negative controls, we constructed TO10 (⌬cydD) and TO4 (⌬cysB), which exhibit defective swarming (30,48,60), and verified their impaired swarming (data not shown). To ensure that the mutant phenotype is specific to swarming motility, we inoculated the strains on swimming motility plates containing 0.25% agar.…”

Section: Resultsmentioning

confidence: 99%

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Cysteine Catabolism and Cysteine Desulfhydrase (CdsH/STM0458) in Salmonella enterica Serovar Typhimurium

2012

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Cysteine is potentially toxic and can affect diverse functions such as oxidative stress, antibiotic resistance, and swarming motility. The contribution of cysteine catabolism in modulating responses to cysteine has not been examined, in part because the genes have not been identified and mutants lacking these genes have not been isolated or characterized. We identified the gene for a previously described cysteine desulfhydrase, which we designated cdsH (formerly STM0458). We also identified a divergently transcribed gene that regulates cdsH expression, which we designated cutR (formerly ybaO, or STM0459). CdsH appears to be the major cysteine-degrading and sulfide-producing enzyme aerobically but not anaerobically. Mutants with deletions of cdsH and ybaO exhibited increased sensitivity to cysteine toxicity and altered swarming motility but unaltered cysteine-enhanced antibiotic resistance and survival in macrophages. Cysteine desulfhydrase (CDS) degrades cysteine to pyruvate, ammonia, and sulfide (19,26,43). The major CDS in Escherichia coli appears to be tryptophanase (TnaA), which has an apparent K m for cysteine of 11 mM (56). TnaA primarily catabolizes tryptophan, which appears to be abundant in the intestinal tract (29). In E. coli, TnaA can become 10% of soluble protein, which suggests the potential to also degrade cysteine in vivo, despite an unfavorable K m (56). Several factors regulate TnaA expression. TnaA is repressed by glucose, pyruvate, and acetate (6, 9, 10, 31). Expression requires cyclic AMP and is induced by tryptophan, cysteine, indole, growth in alkaline broth, depletion of heme and phosphatidyl glycerol, and anaerobic growth with an alternate electron acceptor (9, 51, 52). From these factors, it could be speculated that TnaA contributes to energy generation by degrading tryptophan and possibly cysteine to pyruvate.Salmonella enterica does not have TnaA, yet cysteine induces a powerful CDS (19,26,43). This CDS has been purified from S. enterica, and similarly to TnaA, it contains pyridoxal-5=-phosphate (42). The k cat /K m ratio for L-cysteine, a measure of catalytic efficiency, is 10,340 mM Ϫ1 s Ϫ1 for S. enterica CDS (calculated from values reported by Kredich et al. [42,43]) and 6.7 mM Ϫ1 s Ϫ1for E. coli TnaA (calculated from values reported by Snell [56]). In other words, the S. enterica CDS appears to be more than three orders of magnitude more efficient than TnaA. To explore the function of the S. enterica CDS and cysteine catabolism, we identified the gene for the major CDS and characterized its regulation and the phenotype of mutants lacking this enzyme. MATERIALS AND METHODSStrains and plasmids. Table 1 lists the strains and plasmids used in this study. All gene deletions and replacements were performed originally into the TT22971 background strain as described previously (21), followed by P22 transduction into the appropriate genetic background, and the products were ensured to be phage free by cross-streaking against P22-H5 on green plate agar (15). The following codons were delet...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Cysteine Catabolism and Cysteine Desulfhydrase (CdsH/STM0458) in Salmonella enterica Serovar Typhimurium

2012

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“…Indeed, it has been demonstrated that deletion of genes belonging to the cysteine biosynthetic pathway leads to a bacterial phenotype with reduced virulence, compromised fitness and a susceptibility to antibiotics several fold higher than the wild strains 8,9 . The recent disclosure of a number of additional moonlighting activities of OASS, specifically for OASS-A isoform, that is, toxin activation in some strains of Escherichia coli (E. coli) 10 , gene expression in Bacillus subtilis (B. subtilis) 11 , and the involvement of the enzyme in some pathologically relevant processes as the formation of biofilm and swarming motility, has further focused the interest of researchers toward these proteins [11][12][13][14][15][16][17][18] . These activities span from toxin activation in contact-dependent growth inhibition of uropathogenic E. coli strains 10 , to gene expression in B. subtilis 11 and the involvement of the enzyme in some pathologically-relevant processes as the formation of biofilm and swarming motility 19 .…”

Section: Introductionmentioning

confidence: 99%

Cyclopropane-1,2-dicarboxylic acids as new tools for the biophysical investigation ofO-acetylserine sulfhydrylases by fluorimetric methods and saturation transfer difference (STD) NMR

Annunziato¹,

Pieroni²,

Benoni

et al. 2016

Journal of Enzyme Inhibition and Medicinal Chemistry

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Cysteine is a building block for many biomolecules that are crucial for living organisms. O-Acetylserine sulfhydrylase (OASS), present in bacteria and plants but absent in mammals, catalyzes the last step of cysteine biosynthesis. This enzyme has been deeply investigated because, beside the biosynthesis of cysteine, it exerts a series of ''moonlighting'' activities in bacteria. We have previously reported a series of molecules capable of inhibiting Salmonella typhimurium (S. typhymurium) OASS isoforms at nanomolar concentrations, using a combination of computational and spectroscopic approaches. The cyclopropane-1,2-dicarboxylic acids presented herein provide further insights into the binding mode of small molecules to OASS enzymes. Saturation transfer difference NMR (STD-NMR) was used to characterize the molecule/ enzyme interactions for both OASS-A and B. Most of the compounds induce a several fold increase in fluorescence emission of the pyridoxal 5 0 -phosphate (PLP) coenzyme upon binding to either OASS-A or OASS-B, making these compounds excellent tools for the development of competition-binding experiments.

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“…It was recently demonstrated that this dedicated cysteine desulfhydrase (CDS; EC 2.5.1.47) is encoded by stm0458, which was renamed cdsH (25). CDS is thought to participate in the detoxification of excess cysteine (26), and recent reports suggest an additional role for this enzyme in maintaining sulfide concentrations at a high enough level to support antibiotic resistance and pathogenesis (25,30,31). In general, a PLP-dependent CDS performs chemistry similar to that of IlvA, catalyzing ␤-elimination of the sulfhydryl group from cysteine, yielding sulfide, ammonia, and pyruvate (26,29).…”

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confidence: 99%

Endogenous Synthesis of 2-Aminoacrylate Contributes to Cysteine Sensitivity in Salmonella enterica

et al. 2014

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RidA, the archetype member of the widely conserved RidA/YER057c/UK114 family of proteins, prevents reactive enamine/imine intermediates from accumulating in Salmonella enterica by catalyzing their hydrolysis to stable keto acid products. In the absence of RidA, endogenous 2-aminoacrylate persists in the cellular environment long enough to damage a growing list of essential metabolic enzymes. Prior studies have focused on the dehydration of serine by the pyridoxal 5=-phosphate (PLP)-dependent serine/threonine dehydratases, IlvA and TdcB, as sources of endogenous 2-aminoacrylate. The current study describes an additional source of endogenous 2-aminoacrylate derived from cysteine. The results of in vivo analysis show that the cysteine sensitivity of a ridA strain is contingent upon CdsH, the predominant cysteine desulfhydrase in S. enterica. The impact of cysteine on 2-aminoacrylate accumulation is shown to be unaffected by the presence of serine/threonine dehydratases, revealing another mechanism of endogenous 2-aminoacrylate production. Experiments in vitro suggest that 2-aminoacrylate is released from CdsH following cysteine desulfhydration, resulting in an unbound aminoacrylate substrate for RidA. This work expands our understanding of the role played by RidA in preventing enamine stress resulting from multiple normal metabolic processes.

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l-Cysteine is required for induced antibiotic resistance in actively swarming Salmonella enterica serovar Typhimurium

Cited by 71 publications

References 40 publications

Cysteine Catabolism and Cysteine Desulfhydrase (CdsH/STM0458) in Salmonella enterica Serovar Typhimurium

Cysteine Catabolism and Cysteine Desulfhydrase (CdsH/STM0458) in Salmonella enterica Serovar Typhimurium

Cyclopropane-1,2-dicarboxylic acids as new tools for the biophysical investigation ofO-acetylserine sulfhydrylases by fluorimetric methods and saturation transfer difference (STD) NMR

Endogenous Synthesis of 2-Aminoacrylate Contributes to Cysteine Sensitivity in Salmonella enterica

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