The Staphylococcus aureus thiol/oxidative stress global regulator Spx controls trfA, a gene implicated in cell wall antibiotic resistance
| Autor: | William L. Kelley, Ambre Jousselin, Adriana Renzoni, Daniel Pablo Lew, Christine Barras |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Staphylococcus aureus
Transcription Genetic Molecular Sequence Data Oxidative Stress/genetics Cell Wall/drug effects/genetics Bacillus subtilis Biology Methicillin Resistance/genetics medicine.disease_cause Microbiology Anti-Bacterial Agents/pharmacology Staphylococcus aureus/drug effects/isolation & purification/metabolism 03 medical and health sciences Bacterial Proteins Rapid amplification of cDNA ends Cell Wall Mechanisms of Resistance Sulfhydryl Compounds/metabolism Drug Resistance Multiple Bacterial Gene expression medicine Transcriptional regulation Pharmacology (medical) Sulfhydryl Compounds Membrane Proteins/genetics Oxacillin/pharmacology Promoter Regions Genetic Gene Oxacillin 030304 developmental biology Pharmacology Regulation of gene expression ddc:616 0303 health sciences Base Sequence 030306 microbiology Membrane Proteins Promoter Gene Expression Regulation Bacterial Sequence Analysis DNA biology.organism_classification Anti-Bacterial Agents Drug Resistance Multiple Bacterial/genetics Oxidative Stress Infectious Diseases Bacterial Proteins/genetics/metabolism Methicillin Resistance |
| Zdroj: | Antimicrobial Agents and Chemotherapy, Vol. 57, No 7 (2013) pp. 3283-92 Antimicrobial Agents and Chemotherapy |
| ISSN: | 0066-4804 |
| Popis: | S. aureus combats cell wall antibiotic stress by altered gene expression mediated by various environmental signal sensors. In this study, we examined the transcriptional regulation of trfA , a gene related to mecA of Bacillus subtilis encoding an adaptor protein implicated in multiple roles, notably, proteolysis and genetic competence. Despite strong sequence similarity to B. subtilis mecA , the function of S. aureus trfA remains largely unexplored; however, its deletion leads to almost complete loss of resistance to oxacillin and glycopeptide antibiotics in glycopeptide-intermediate S. aureus (GISA) derivatives of methicillin-susceptible or methicillin-resistant S. aureus (MRSA) clinical or laboratory isolates. Northern blot analysis and 5′ rapid amplification of cDNA ends (RACE) mapping revealed that trfA was expressed monocistronically by three promoters. Cell wall-active antibiotic exposure led to both increased trfA transcription and enhanced steady-state TrfA levels. trfA promoter regulation was not dependent upon the cell wall stress sentinel VraSR and other sensory stress systems, such as GraRS, WalkRK, Stk1/Stp1, and SigB. Notably, we discovered that the global oxidative-stress regulator Spx controlled trfA transcription. This finding was also confirmed using a strain with enhanced Spx levels resulting from a defect in yjbH , encoding a Spx-interacting protein governing Spx proteolytic degradation. A cohort of clinical GISA strains revealed significant steady-state upregulation of trfA compared to corresponding susceptible parental strains, further supporting a role for trfA in antibiotic resistance. These data provide strong evidence for a link between cell wall antibiotic stress and evoked responses mediated by an oxidative-stress sensor. |
| Databáze: | OpenAIRE |
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