Glutathione in Bacteria

Смирнова, Г. В.; Oktyabrsky, Oleg N.

doi:10.1007/s10541-005-0248-3

Cited by 161 publications

(167 citation statements)

References 131 publications

(157 reference statements)

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“…However, in addition to being able to be metabolized into H 2 S, glutathione and its catabolic intermediate CysGly have been shown to have important functions in other bacteria (51). Both glutathione and Cys-Gly can play critical roles in maintaining or altering the redox status of a cell and can help protect components of the cell from oxidative damage.…”

Section: Discussionmentioning

confidence: 99%

A 52-kDa Leucyl Aminopeptidase from Treponema denticola Is a Cysteinylglycinase That Mediates the Second Step of Glutathione Metabolism

Chu

Lai

et al. 2008

Journal of Biological Chemistry

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The metabolism of glutathione by the periodontal pathogen Treponema denticola produces hydrogen sulfide, which may play a role in the host tissue destruction seen in periodontitis. H 2 S production in this organism has been proposed to occur via a three enzyme pathway, ␥-glutamyltransferase, cysteinylglycinase (CGase), and cystalysin. In this study, we describe the purification and characterization of T. denticola CGase. Standard approaches were used to purify a 52-kDa CGase activity from T. denticola, and high pressure liquid chromatography electrospray ionization tandem mass spectrometry analysis of this molecule showed that it matches the amino acid sequence of a predicted 52-kDa protein in the T. denticola genome data base. A recombinant version of this protein was overexpressed in and purified from Escherichia coli and shown to catalyze the hydrolysis of cysteinylglycine (Cys-Gly) with the same kinetics as the native protein. . Importantly, in combination with the two other previously purified T. denticola enzymes, ␥-glutamyltransferase and cystalysin, CGase mediates the in vitro degradation of glutathione into the expected end products, including H 2 S. These results prove that T. denticola contains the entire three-step pathway to produce H 2 S from glutathione, which may be important for pathogenesis.The volatile sulfur compound H 2 S can be produced by the metabolic activity of numerous oral bacteria, including several periodontal pathogens (1-3). This gas, which is malodorous and highly toxic (4 -6), is found in high concentrations in periodontal pockets (7-9) and may play a role in some of the tissue destruction seen in periodontal diseases (7,8,10). H 2 S can be produced from the metabolism of several molecules, but glutathione (L-␥-glutamyl-L-cysteinylglycine) is believed to be the major source for H 2 S production in the oral cavity; human cells, especially polymorphonuclear leucocytes, have high concentrations (up to 4 mM) of glutathione that can be released when host cells are damaged in the periodontal pocket. Although a number of oral bacteria have been tested, only a few of them are able to catabolize glutathione into H 2 S (3, 11, 12). Treponema denticola, which appears to play a significant role in the development of acute and chronic periodontal diseases in humans (13-17), is the only oral pathogen in which the proteins involved in this catabolic pathway have begun to be identified and characterized (18 -22). Glutathione catabolism to H 2 S (and glutamate, glycine, ammonia, and pyruvate) has been proposed to occur via a three-step enzyme pathway in this spirochete (12). In the first step, glutathione is split into glutamate and Cys-Gly. This dipeptide is then hydrolyzed into glycine and L-cysteine followed by the breakdown of L-cysteine into pyruvate, ammonia, and H 2 S. The enzymes involved in the first and third steps have been purified from T. denticola and characterized (19 -30). ␥-Glutamyltransferase (GGT) 2 is a 27-kDa protein that catalyzes the cleavage of glutathione into glutamate ...

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Section: Discussionmentioning

confidence: 99%

A 52-kDa Leucyl Aminopeptidase from Treponema denticola Is a Cysteinylglycinase That Mediates the Second Step of Glutathione Metabolism

Chu

Lai

et al. 2008

Journal of Biological Chemistry

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“…In other bacteria, these genes have been shown to enhance fitness under nutrient and temperature stress (31) (Dataset S2). Protein quality control, involving genes for protein recycling (clpS, htpX, lon, and tldD) and stabilization (dsbC and pcm), also appeared important in vivo, as were genes for the synthesis (gshAB) and activity (gstA) of glutathione, an antioxidant that contributes to general stress tolerance and detoxification (32).…”

Section: Significancementioning

confidence: 99%

Genome-wide screen identifies host colonization determinants in a bacterial gut symbiont

Powell

Leonard

Kwong

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

133

152

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Animal guts are often colonized by host-specialized bacterial species to the exclusion of other transient microorganisms, but the genetic basis of colonization ability is largely unknown. The bacterium Snodgrassella alvi is a dominant gut symbiont in honey bees, specialized in colonizing the hindgut epithelium. We developed methods for transposon-based mutagenesis in S. alvi and, using high-throughput DNA sequencing, screened genome-wide transposon insertion (Tnseq) and transcriptome (RNA-seq) libraries to characterize both the essential genome and the genes facilitating host colonization. Comparison of Tn-seq results from laboratory cultures and from monoinoculated worker bees reveal that 519 of 2,226 protein-coding genes in S. alvi are essential in culture, whereas 399 are not essential but are beneficial for gut colonization. Genes facilitating colonization fall into three broad functional categories: extracellular interactions, metabolism, and stress responses. Extracellular components with strong fitness benefits in vivo include trimeric autotransporter adhesins, O antigens, and type IV pili (T4P). Experiments with T4P mutants establish that T4P in S. alvi likely function in attachment and biofilm formation, with knockouts experiencing a competitive disadvantage in vivo. Metabolic processes promoting colonization include essential amino acid biosynthesis and iron acquisition pathways, implying nutrient scarcity within the hindgut environment. Mechanisms to deal with various stressors, such as for the repair of double-stranded DNA breaks and protein quality control, are also critical in vivo. This genome-wide study identifies numerous genetic networks underlying colonization by a gut commensal in its native host environment, including some known from more targeted studies in other hostmicrobe symbioses.type IV pilus | transposon mutagenesis | microbiota | symbiosis | Neisseriaceae

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“…The role of MexT in protecting against redox imbalances generated by the disulfide stress elicitor diamide [diazenedicarboxylic acid bis(N,N,-di-methylamide)] was determined, and the ability of diamide to induce MexT-regulated targets was investigated. Disulfide stress is a subcategory of oxidative stress caused by perturbation of the thiol-disulfide balance in the cytoplasm, which can arise due to the accumulation of thiol-reactive compounds such as quinones (34,58). Diamide reacts readily with free thiols, causing thiol-disulfide imbalances in the cytoplasm and the formation of aberrant disulfide bonds (25,58).…”

mentioning

confidence: 99%

“…Disulfide stress is a subcategory of oxidative stress caused by perturbation of the thiol-disulfide balance in the cytoplasm, which can arise due to the accumulation of thiol-reactive compounds such as quinones (34,58). Diamide reacts readily with free thiols, causing thiol-disulfide imbalances in the cytoplasm and the formation of aberrant disulfide bonds (25,58). Diamide thus simulates stress-inducing redox imbalances caused by naturally occurring electrophiles.…”

mentioning

confidence: 99%

MexT Functions as a Redox-Responsive Regulator Modulating Disulfide Stress Resistance in Pseudomonas aeruginosa

et al. 2012

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MexT is a global LysR transcriptional regulator known to modulate antibiotic resistance and virulence in Pseudomonas aeruginosa. In this study, a novel role for MexT in mediating intrinsic disulfide stress resistance was demonstrated, representing the first identified phenotype associated with inactivation of this regulator in wild-type cells. Disruption of mexT resulted in increased susceptibility to the disulfide stress elicitor diamide [diazenedicarboxylic acid bis(N,N,-di-methylamide)]. This compound is known to elicit a specific stress response via depletion of reduced glutathione and alteration of the cellular redox environment, implicating MexT in redox control. In support of this, MexT-regulated targets, including the MexEF-OprN multidrug efflux system, were induced by subinhibitory concentrations of diamide. A mexF insertion mutant also exhibited increased diamide susceptibility, implicating the MexEF-OprN efflux system in MexT-associated disulfide stress resistance. Purified MexT protein was observed to form an oligomeric complex in the presence of oxidized glutathione, with a calculated redox potential of ؊189 mV. This value far exceeds the thiol-disulfide redox potential of the bacterial cytoplasm, ensuring that MexT remains reduced under normal physiological conditions. MexT is activated by mutational disruption of the predicted quinone oxidoreductase encoded by mexS. Alterations in the cellular redox state were observed in a mexS mutant (PA14nfxC), supporting a model whereby the perception of MexS-associated redox signals by MexT leads to the induction of the MexEF-OprN efflux system, which, in turn, may mediate disulfide stress resistance via efflux of electrophilic compounds.

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Glutathione in Bacteria

Cited by 161 publications

References 131 publications

A 52-kDa Leucyl Aminopeptidase from Treponema denticola Is a Cysteinylglycinase That Mediates the Second Step of Glutathione Metabolism

A 52-kDa Leucyl Aminopeptidase from Treponema denticola Is a Cysteinylglycinase That Mediates the Second Step of Glutathione Metabolism

Genome-wide screen identifies host colonization determinants in a bacterial gut symbiont

MexT Functions as a Redox-Responsive Regulator Modulating Disulfide Stress Resistance in Pseudomonas aeruginosa

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