Antioxidant Functions of Nitric Oxide Synthase in a Methicillin Sensitive<i>Staphylococcus aureus</i>

Vaish, Manisha; Singh, Vipender

doi:10.1155/2013/312146

Cited by 19 publications

(19 citation statements)

References 30 publications

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“…Many studies that proposed to identify and characterize major components in the oxidative stress response of S. aureus used SH1000 as their model strain (28,43,(57)(58)(59). One consideration raised by our studies into the role of BSH in the oxidative stress response is whether the results of studies conducted in SH1000 or in strains of the 8325 lineage, such as RN6390 and RN4220, which do not produce BSH, are reflective of the results that would be obtained with clinical isolates.…”

Section: Figmentioning

confidence: 99%

Importance of Bacillithiol in the Oxidative Stress Response of Staphylococcus aureus

et al. 2014

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In Staphylococcus aureus, the low-molecular-weight thiol called bacillithiol (BSH), together with cognate S-transferases, is believed to be the counterpart to the glutathione system of other organisms. To explore the physiological role of BSH in S. aureus, we constructed mutants with the deletion of bshA (sa1291), which encodes the glycosyltransferase that catalyzes the first step of BSH biosynthesis, and fosB (sa2124), which encodes a BSH-S-transferase that confers fosfomycin resistance, in several S. aureus strains, including clinical isolates. Mutation of fosB or bshA caused a 16-to 60-fold reduction in fosfomycin resistance in these S. aureus strains. High-pressure liquid chromatography analysis, which quantified thiol extracts, revealed some variability in the amounts of BSH present across S. aureus strains. Deletion of fosB led to a decrease in BSH levels. The fosB and bshA mutants of strain COL and a USA300 isolate, upon further characterization, were found to be sensitive to H 2 O 2 and exhibited decreased NADPH levels compared with those in the isogenic parents. Microarray analyses of COL and the isogenic bshA mutant revealed increased expression of genes involved in staphyloxanthin synthesis in the bshA mutant relative to that in COL under thiol stress conditions. However, the bshA mutant of COL demonstrated decreased survival compared to that of the parent in human wholeblood survival assays; likewise, the naturally BSH-deficient strain SH1000 survived less well than its BSH-producing isogenic counterpart. Thus, the survival of S. aureus under oxidative stress is facilitated by BSH, possibly via a FosB-mediated mechanism, independently of its capability to produce staphyloxanthin.

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Section: Figmentioning

confidence: 99%

Importance of Bacillithiol in the Oxidative Stress Response of Staphylococcus aureus

et al. 2014

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“…[147][148][149] The S. aureus nitric oxide synthase also protects against killing by neutrophils, as well as being involved in the development of skin abscesses in a mouse model. [150][151][152] Staphylococcus aureus is tolerant to nitrosative stress by transcriptional reprogramming that involves at least 84 identified genes, many of which have roles in iron-homeostasis and hypoxic metabolism; the latter falling under the influence of the indirect O 2 -responsive SrrAB two-component system (see above). Consequently, an srrAB mutant exhibited enhanced sensitivity to NO and this was partially attributed to dysregulation of the NO detoxification enzyme Hmp (see above), but the divergently transcribed ldh1 gene, encoding lactate dehydrogenase was subsequently shown to be essential for virulence and maintaining redox balance during nitrosative stress.…”

Section: Nitric Oxide Responsesmentioning

confidence: 99%

Transcriptional regulation of bacterial virulence gene expression by molecular oxygen and nitric oxide

2014

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Molecular oxygen (O 2 ) and nitric oxide (NO) are diatomic gases that play major roles in infection. The host innate immune system generates reactive oxygen species and NO as bacteriocidal agents and both require O 2 for their production. Furthermore, the ability to adapt to changes in O 2 availability is crucial for many bacterial pathogens, as many niches within a host are hypoxic. Pathogenic bacteria have evolved transcriptional regulatory systems that perceive these gases and respond by reprogramming gene expression. Direct sensors possess iron-containing co-factors (iron-sulfur clusters, mononuclear iron, heme) or reactive cysteine thiols that react with O 2 and/or NO. Indirect sensors perceive the physiological effects of O 2 starvation. Thus, O 2 and NO act as environmental cues that trigger the coordinated expression of virulence genes and metabolic adaptations necessary for survival within a host. Here, the mechanisms of signal perception by key O 2 -and NO-responsive bacterial transcription factors and the effects on virulence gene expression are reviewed, followed by consideration of these aspects of gene regulation in two major pathogens, Staphylococcus aureus and Mycobacterium tuberculosis.

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“…NOS is involved in the production of NO by Bacillus subtilis (Gusarov and Nudler, 2005; Gusarov et al, 2008), Bacillus anthracis (Shatalin et al, 2008), Bacillus cereus (Montgomery et al, 2010), Geobacillus stearothermophilus (Kabir et al, 2008), Streptomyces turgidiscabies (Kers et al, 2004), Deinococcus radiodurans (Patel et al, 2009), and Staphylococcus aureus (van Sorge et al, 2013). S. aureus NOS is involved in resistance to oxidative stress and antibiotics, and virulence (Vaish and Singh, 2013; van Sorge et al, 2013; Sapp et al, 2014). In all sequenced S. aureus genomes, the nos gene is part of a cluster containing another gene encoding a prephenate dehydratase, which is involved in phenylalanine biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

Evidence for Nitric Oxide Synthase Activity in Staphylococcus xylosus Mediating Nitrosoheme Formation

Ras

Zuliani²,

Derkx

et al. 2017

Front. Microbiol.

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Staphylococcus xylosus is used as a starter culture in fermented meat products and contributes to color formation by the reduction of nitrate to nitrite. Nitrite is a food additive that is chemically turned to nitric oxide (NO) in meat but its safety has been questioned. The objective of this study was to determine the ability of NO synthase (NOS) of S. xylosus C2a to produce NO. For this purpose, a nos deletion mutant (Δnos) in S. xylosus was constructed and NO production was evaluated in a test based on its ability to form nitrosomyoglobin and nitrosoheme. Production of NO was abrogated in the Δnos mutant under aerobic conditions and reduced about 35-40% comparing to the wild type C2a under limited oxygenation. This mutant was sensitive to oxidative stress. The expression of genes encoding catalase was modulated in the mutant with an up-regulation of katA and a down-regulation of katB and katC. The Δnos mutant displayed high colony pigmentation after prolonged growth on agar medium. Finally, the Δnos mutant showed no growth in minimal medium. Growth was not restored in the minimal medium by complementation with nos, but was restored by either addition of phenylalanine or complementation with pdt, a gene that encodes a prephenate dehydratase involved in phenylalanine biosynthesis and co-transcribed with nos. Our findings clearly demonstrate NOS-mediated NO production in S. xylosus, a meat-associated coagulase-negative Staphylococcus.

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Antioxidant Functions of Nitric Oxide Synthase in a Methicillin SensitiveStaphylococcus aureus

Cited by 19 publications

References 30 publications

Importance of Bacillithiol in the Oxidative Stress Response of Staphylococcus aureus

Importance of Bacillithiol in the Oxidative Stress Response of Staphylococcus aureus

Transcriptional regulation of bacterial virulence gene expression by molecular oxygen and nitric oxide

Evidence for Nitric Oxide Synthase Activity in Staphylococcus xylosus Mediating Nitrosoheme Formation

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