Bicarbonate Resensitization of Methicillin-Resistant <i>Staphylococcus aureus</i> to β-Lactam Antibiotics.
Ersoy. Selvi C SC; Abdelhady. Wessam W; Li. Liang L; Chambers. Henry F HF; Xiong. Yan Q YQ; Bayer. Arnold S AS
Key Findings
- Sodium bicarbonate in testing media reveals a subset of MRSA strains that become susceptible to β‑lactam antibiotics (oxacillin, cefazolin).
- Bicarbonate lowers expression of mecA and sarA genes, reducing the resistance protein PBP2a in responsive strains.
- In bicarbonate‑supplemented conditions, β‑lactams work synergistically with the host peptide LL‑37 to kill the responsive MRSA strains.
Practical Outcomes
- Testing MRSA isolates with bicarbonate could identify infections treatable with standard β‑lactams, potentially avoiding more toxic or expensive drugs. However, clinical protocols for using bicarbonate or LL‑37 in patients are not established, so this insight is mainly useful for informing future research and discussions with healthcare providers.
Summary
The study shows that adding sodium bicarbonate (baking‑soda) to lab tests can make some MRSA bacteria become sensitive again to common antibiotics like oxacillin and cefazolin, especially when the natural immune peptide LL‑37 is present. This suggests a possible way to treat certain MRSA infections with cheaper, less toxic drugs, but it’s still early‑stage research and not a ready‑to‑use protocol for people.
Abstract
Endovascular infections caused by methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) are a major health care concern, especially infective endocarditis (IE). Standard antimicrobial susceptibility testing (AST) defines most MRSA strains as "resistant" to β-lactams, often leading to the use of costly and/or toxic treatment regimens. In this investigation, five prototype MRSA strains, representing the range of genotypes in current clinical circulation, were studied. We identified two distinct MRSA phenotypes upon AST using standard media, with or without sodium bicarbonate (NaHCO<sub>3</sub>) supplementation: one highly susceptible to the antistaphylococcal β-lactams oxacillin and cefazolin (NaHCO<sub>3</sub> responsive) and one resistant to such agents (NaHCO<sub>3</sub> nonresponsive). These phenotypes accurately predicted clearance profiles of MRSA from target tissues in experimental MRSA IE treated with each β-lactam. Mechanistically, NaHCO<sub>3</sub> reduced the expression of two key genes involved in the MRSA phenotype, <i>mecA</i> and <i>sarA</i>, leading to decreased production of penicillin-binding protein 2a (that mediates methicillin resistance), in NaHCO<sub>3</sub>-responsive (but not in NaHCO<sub>3</sub>-nonresponsive) strains. Moreover, both cefazolin and oxacillin synergistically killed NaHCO<sub>3</sub>-responsive strains in the presence of the host defense antimicrobial peptide (LL-37) in NaHCO<sub>3</sub>-supplemented media. These findings suggest that AST of MRSA strains in NaHCO<sub>3</sub>-containing media may potentially identify infections caused by NaHCO<sub>3</sub>-responsive strains that are appropriate for β-lactam therapy.
Study Information
pubmed
2019
2019-06-24T00:00:00.000Z
10.1128/aac.00496-19