Reactive oxygen species are the major antibacterials against Salmonella Typhimurium purine auxotrophs in the phagosome of RAW 264.7 cells

Mantena, Radha Kr; Wijburg, Odilia L. C.; Vindurampulle, Christofer J.; Bennett-Wood, Vicki; Walduck, Anna; Drummond, Grant Raymond; Davies, John K.; Robins-Browne, Roy M.; Strugnell, Richard A.

doi:10.1111/j.1462-5822.2007.01105.x

Cited by 53 publications

(25 citation statements)

References 61 publications

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“…5C), SAV0862 (1), clpx (15), clp (15), sodA (24), srtA (22), ftsH (28), srrA (42), saeR-saeS (27), sarZ (7), sarA (4), sigB (21), rsbU (21), sucB (35), and dnaD (11), has been shown to result in attenuated virulence of S. aureus in vivo. Thus, the dramatic virulence attenuation of purA and purH mutant strains is most likely due to a combination of several effects, including nutrient limitation, energy metabolism, stress response, and altered (34). In the current study, the expression of 23 genes involved in DNA repair is also affected by purA or purH mutation (see Table S1).…”

Section: Discussionmentioning

confidence: 65%

Golden Pigment Production and Virulence Gene Expression Are Affected by Metabolisms in Staphylococcus aureus

Lan¹,

et al. 2010

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The pathogenesis of staphylococcal infections is multifactorial. Golden pigment is an eponymous feature of the human pathogen Staphylococcus aureus that shields the microbe from oxidation-based clearance, an innate host immune response to infection. Here, we screened a collection of S. aureus transposon mutants for pigment production variants. A total of 15 previously unidentified genes were discovered. Notably, disrupting metabolic pathways such as the tricarboxylic acid cycle, purine biosynthesis, and oxidative phosphorylation yields mutants with enhanced pigmentation. The dramatic effect on pigment production seems to correlate with altered expression of virulence determinants. Microarray analysis further indicates that purine biosynthesis impacts the expression of ϳ400 genes involved in a broad spectrum of functions including virulence. The purine biosynthesis mutant and oxidative phosphorylation mutant strains exhibit significantly attenuated virulence in a murine abscess model of infection. Inhibition of purine biosynthesis with a known smallmolecule inhibitor results in altered virulence gene expression and virulence attenuation during infection. Taken together, these results suggest an intimate link between metabolic processes and virulence gene expression in S. aureus. This study also establishes the importance of purine biosynthesis and oxidative phosphorylation for in vivo survival.Staphylococcus aureus causes a variety of infections in humans, ranging from minor skin and wound infections to lifethreatening diseases (31). The pathogenesis of staphylococcal infections is a multifactorial process that depends on the expression of different virulence factors controlled by multiple regulatory systems in conjunction with environmental and nutritional signals (46). The high degree of variability in the expression of virulence genes is modulated by a complex network regulated by factors such as the agr locus (RNAIII), SarA, and SigB (5, 9), which allows the bacterium to adapt to changing environmental conditions for survival and developing infection.The species epithet of S. aureus reflects its characteristic surface pigmentation (aureus, meaning "golden" in Latin) (43). The yellowish-orange (golden) pigment produced by S. aureus has been linked to virulence, owing to its antioxidant property (29,30). The golden pigmentation of S. aureus is the product of a C 30 triterpenoid carotenoid biosynthesis pathway, and the carotenoid pigment biosynthesis genes are organized in an operon crtOPQMN controlled by the alternative sigma factor SigB (3, 39). Since many virulence genes are coordinately regulated in S. aureus (5, 9, 31), we hypothesized that genes affecting pigmentation may also influence the production of virulence determinants and have an impact on the pathogenesis of S. aureus.Herein, we present an analysis of S. aureus golden pigment biosynthesis and regulatory pathways at the genomic level by screening the Phoenix (⌽N⌶) library, a collection of defined transposon insertions into 1,812 open reading frame...

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Section: Discussionmentioning

confidence: 65%

Golden Pigment Production and Virulence Gene Expression Are Affected by Metabolisms in Staphylococcus aureus

Lan¹,

et al. 2010

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“…ROS, such as O 2 -, OH -and H 2 O 2 , are highly genotoxic/ mutagenic and harmful to cellular macromolecules such as DNA, proteins and lipids [2] . The adverse effect is represented by the oxidative stress that can arise from a lack of antioxidant defence or by an increase of oxidative processes in the body [3] .…”

Section: Introductionmentioning

confidence: 99%

Evaluation of antigenotoxic effects of carotenoids from green algae Chlorococcum humicola using human lymphocytes

Bhagavathy

Sumathi²

2012

Asian Pacific Journal of Tropical Biomedicine

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“…Thus, many virulence genes are integrated into "housekeeping" gene regulatory networks, coded for by a core genome, which steer bacterial stress responses (12,17,27,55). Selected anabolic pathways also contribute to virulence of S. serovar Typhimurium (18,27), evidently by providing biochemical building blocks for bacterial replication (36).…”

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confidence: 99%

Thioredoxin 1 Participates in the Activity of theSalmonella entericaSerovar Typhimurium Pathogenicity Island 2 Type III Secretion System

et al. 2009

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The facultative intracellular pathogen Salmonella enterica serovar Typhimurium relies on its Salmonella pathogenicity island 2 (SPI2) type III secretion system (T3SS) for intracellular replication and virulence. We report that the oxidoreductase thioredoxin 1 (TrxA) and SPI2 are coinduced for expression under in vitro conditions that mimic an intravacuolar environment, that TrxA is needed for proper SPI2 activity under these conditions, and that TrxA is indispensable for SPI2 activity in both phagocytic and epithelial cells. Infection experiments in mice demonstrated that SPI2 strongly contributed to virulence in a TrxA-proficient background whereas SPI2 did not affect virulence in a trxA mutant. Complementation analyses using wild-type trxA or a genetically engineered trxA coding for noncatalytic TrxA showed that the catalytic activity of TrxA is essential for SPI2 activity in phagocytic cells whereas a noncatalytic variant of TrxA partially sustained SPI2 activity in epithelial cells and virulence in mice. These results show that TrxA is needed for the intracellular induction of SPI2 and provide new insights into the functional integration between catalytic and noncatalytic activities of TrxA and a bacterial T3SS in different settings of intracellular infections.

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Reactive oxygen species are the major antibacterials against Salmonella Typhimurium purine auxotrophs in the phagosome of RAW 264.7 cells

Cited by 53 publications

References 61 publications

Golden Pigment Production and Virulence Gene Expression Are Affected by Metabolisms in Staphylococcus aureus

Golden Pigment Production and Virulence Gene Expression Are Affected by Metabolisms in Staphylococcus aureus

Evaluation of antigenotoxic effects of carotenoids from green algae Chlorococcum humicola using human lymphocytes

Thioredoxin 1 Participates in the Activity of theSalmonella entericaSerovar Typhimurium Pathogenicity Island 2 Type III Secretion System

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