Impact of Bicarbonate-β-Lactam Exposures on Methicillin-Resistant <i>Staphylococcus aureus</i> (MRSA) Gene Expression in Bicarbonate-β-Lactam-Responsive vs. Non-Responsive Strains
Methicillin-resistant <i>Staphylococcus aureu</i><i>s</i> (MRSA) infections represent a difficult clinical treatment issue. Recently, a novel phenotype was discovered amongst selected MRSA which exhibited enhanced β-lactam susceptibility in vitro in the presence of NaHCO<s...
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| Autores principales: | , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/3a0d850746cb45ea808e50bf8ec72ec5 |
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| Sumario: | Methicillin-resistant <i>Staphylococcus aureu</i><i>s</i> (MRSA) infections represent a difficult clinical treatment issue. Recently, a novel phenotype was discovered amongst selected MRSA which exhibited enhanced β-lactam susceptibility in vitro in the presence of NaHCO<sub>3</sub> (termed ‘NaHCO<sub>3</sub>-responsiveness’). This increased β-lactam susceptibility phenotype has been verified in both ex vivo and in vivo models. Mechanistic studies to-date have implicated NaHCO<sub>3</sub>-mediated repression of genes involved in the production, as well as maturation, of the alternative penicillin-binding protein (PBP) 2a, a necessary component of MRSA β-lactam resistance. Herein, we utilized RNA-sequencing (RNA-seq) to identify genes that were differentially expressed in NaHCO<sub>3</sub>-responsive (MRSA 11/11) vs. non-responsive (COL) strains, in the presence vs. absence of NaHCO<sub>3</sub>-β-lactam co-exposures. These investigations revealed that NaHCO<sub>3</sub> selectively repressed the expression of a cadre of genes in strain 11/11 known to be a part of the <i>sigB</i>-<i>sarA</i>-<i>agr</i> regulon, as well as a number of genes involved in the anchoring of cell wall proteins in MRSA. Moreover, several genes related to autolysis, cell division, and cell wall biosynthesis/remodeling, were also selectively impacted by NaHCO<sub>3</sub>-OXA exposure in the NaHCO<sub>3</sub>-responsive strain MRSA 11/11. These outcomes provide an important framework for further studies to mechanistically verify the functional relevance of these genetic perturbations to the NaHCO<sub>3</sub>-responsiveness phenotype in MRSA. |
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