ArticleThe Journal of infectious diseases2016
The Global Regulon sarA Regulates β-Lactam Antibiotic Resistance in Methicillin-Resistant Staphylococcus aureus In Vitro and in Endovascular Infections.
Article in The Journal of infectious diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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40 citing papers in PubMed, 58 citations in OpenAlex.
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- Berberine hydrochloride reduces staphyloxanthin synthesis by inhibiting fni genes in methicillin-resistant Staphylococcus aureus.Molecular biology reports · 2024Article
- Cinnamaldehyde targets SarA to enhance β-lactam antibiotic activity against methicillin-resistantmLife · 2024Article
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- Molecular Determinants of β-Lactam Resistance in Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2023Review
- Impact of Bicarbonate on PBP2a Production, Maturation, and Functionality in Methicillin-ResistantAntimicrobial agents and chemotherapy · 2023Article
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- Insights into the Effects and Mechanism of Andrographolide-Mediated Recovery of Susceptibility of Methicillin-Resistant Staphylococcus aureus to β-Lactam Antibiotics.Microbiology spectrum · 2023Article
- Study of SarA by DNA Affinity Capture Assay (DACA) Employing Three Promoters of Key Virulence and Resistance Genes in Methicillin-ResistantAntibiotics (Basel, Switzerland) · 2022Article
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Authors and funding
8 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundThe global regulator sarA modulates virulence of methicillin-resistant Staphylococcus aureus (MRSA) via regulation of principal virulence factors (eg, adhesins and toxins) and biofilm formation. Resistance of S. aureus strains to β-lactam antibiotics (eg, oxacillin) depends on the production of penicillin-binding protein 2a (PBP2a), encoded by mecA
methodsIn the present study, we investigated the impact of sarA on the phenotypic and genotypic characteristics of oxacillin resistance both in vitro and in an experimental endocarditis model, using prototypic healthcare- and community-associated MRSA parental and their respective sarA mutant strain sets.
resultsAll sarA mutants (vs respective MRSA parental controls) displayed significant reductions in oxacillin resistance and biofilm formation in vitro and oxacillin persistence in an experimental endocarditis model in vivo. These phenotypes corresponded to reduced mecA expression and PBP2a production and an interdependency of sarA and sigB regulators. Moreover, RNA sequencing analyses showed that sarA mutants exhibited significantly increased levels of primary extracellular proteases and suppressed pyrimidine biosynthetic pathway, argininosuccinate lyase-encoding, and ABC transporter-related genes as compared to the parental strain.
conclusionsThese results suggested that sarA regulates oxacillin resistance in mecA-positive MRSA. Thus, abrogation of this regulator represents an attractive and novel drug target to potentiate efficacy of existing antibiotic for MRSA therapy.
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