Role of the hprT–ftsH locus in Staphylococcus aureus

Lithgow, James K.; Ingham, Eileen; Foster, Simon J.

doi:10.1099/mic.0.26674-0

Cited by 41 publications

(44 citation statements)

References 41 publications

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“…Recently, it was shown that mutation of cysM encoding cysteine synthase caused increased sensitivity of S. aureus to tellurite, hydrogen peroxide, acid, and diamide and also significantly reduced the ability of S. aureus to recover from starvation in amino acid-or phosphate-limiting conditions, indicating that cysteine has a role in the S. aureus oxidant stress response and survival mechanisms (12). Also of interest, mutation of a membrane-bound, ATPand Zn 2ϩ -dependent "AAA-type" protease gene in S. aureus led to pleiotropic defects, including slower growth, sensitivity to salt, acid, methyl viologen, and potassium tellurite stresses, and reduced survival in amino acid-or phosphate-limiting conditions (13). Thus, these data provide further support for the hypothesis that the reduced ⌬⌿ and ATP of the SCVs play a role in the susceptibility of these variants to selenite, tellurite, and nitrite.…”

Section: Discussionmentioning

confidence: 99%

Phenotype Microarray Profiling of Staphylococcus aureus menD and hemB Mutants with the Small-Colony-Variant Phenotype

et al. 2006

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Standard biochemical tests have revealed that hemin and menadione auxotrophic Staphylococcus aureus smallcolony variants (SCVs) exhibit multiple phenotypic changes. To provide a more complete analysis of the SCV phenotype, two genetically defined mutants with a stable SCV phenotype were comprehensively tested. These mutants, generated via mutations in menD or hemB that yielded menadione and hemin auxotrophs, were subjected to phenotype microarray (PM) analysis of over 1,500 phenotypes (including utilization of different carbon, nitrogen, phosphate, and sulfur sources; growth stimulation or inhibition by amino acids and other nutrients, osmolytes, and metabolic inhibitors; and susceptibility to antibiotics). Compared to parent strain COL, the hemB mutant was defective in utilization of a variety of carbon sources, including Krebs cycle intermediates and compounds that ultimately generate ATP via electron transport. The phenotype of the menD mutant was similar to that of the hemB mutant, but the defects in carbon metabolism were more pronounced than those seen with the hemB mutant. In both mutant strains, hexose phosphates and other carbohydrates that provide ATP in the absence of electron transport stimulated growth. Other phenotypes of SCV mutants, such as hypersensitivity to sodium selenite, sodium tellurite, and sodium nitrite, were also uncovered by the PM analysis. Key results of the PM analysis were confirmed in independent growth studies and by using Etest strips for susceptibility testing. PM technology is a new and efficient technology for assessing cellular phenotypes in S. aureus.

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Section: Discussionmentioning

confidence: 99%

Phenotype Microarray Profiling of Staphylococcus aureus menD and hemB Mutants with the Small-Colony-Variant Phenotype

et al. 2006

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“…Inactivation of some of these genes, for instance, qoxB (Fig. 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).…”

Section: Discussionmentioning

confidence: 99%

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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“…Of the three, ClpP appears to have the greatest impact in shaping the S. aureus proteome (14), and when disrupted, it causes significant defects in growth, survival, virulence gene expression, and cell wall maintenance (15,16). FtsH has a modest role in regulating growth, stress resistance, starvation survival, and pathogenicity (17), but with a putative localization to the inner membrane, it is thought to mainly degrade membrane-bound targets. Very little is known about ClpQ, in part because a ⌬clpQ mutant of S. aureus exhibits few phenotypes (18) and shows few alterations to stress responses.…”

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confidence: 99%

Role of Adaptor TrfA and ClpPC in Controlling Levels of SsrA-Tagged Proteins and Antitoxins in Staphylococcus aureus

2014

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bStaphylococcus aureus responds to changing extracellular environments in part by adjusting its proteome through alterations of transcriptional priorities and selective degradation of the preexisting pool of proteins. In Bacillus subtilis, the proteolytic adaptor protein MecA has been shown to play a role in assisting with the proteolytic degradation of proteins involved in competence and the oxidative stress response. However, the targets of TrfA, the MecA homolog in S. aureus, have not been well characterized. In this work, we investigated how TrfA assists chaperones and proteases to regulate the proteolysis of several classes of proteins in S. aureus. By fusing the last 3 amino acids of the SsrA degradation tag to Venus, a rapidly folding yellow fluorescent protein, we obtained both fluorescence-based and Western blot assay-based evidence that TrfA and ClpCP are the adaptor and protease, respectively, responsible for the degradation of the SsrA-tagged protein in S. aureus. Notably, the impact of TrfA on degradation was most prominent during late log phase and early stationary phase, due in part to a combination of transcriptional regulation and proteolytic degradation of TrfA by ClpCP. We also characterized the temporal transcriptional regulation governing TrfA activity, wherein Spx, a redox-sensitive transcriptional regulator degraded by ClpXP, activates trfA transcription while repressing its own promoter. Finally, the scope of TrfA-mediated proteolysis was expanded by identifying TrfA as the adaptor that works with ClpCP to degrade antitoxins in S. aureus. Together, these results indicate that the adaptor TrfA adds temporal nuance to protein degradation by ClpCP in S. aureus.

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Role of the hprT–ftsH locus in Staphylococcus aureus

Cited by 41 publications

References 41 publications

Phenotype Microarray Profiling of Staphylococcus aureus menD and hemB Mutants with the Small-Colony-Variant Phenotype

Phenotype Microarray Profiling of Staphylococcus aureus menD and hemB Mutants with the Small-Colony-Variant Phenotype

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

Role of Adaptor TrfA and ClpPC in Controlling Levels of SsrA-Tagged Proteins and Antitoxins in Staphylococcus aureus

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