Impact of Bicarbonate-β-Lactam Exposures on Methicillin-Resistant Staphylococcus aureus (MRSA) Gene Expression in Bicarbonate-β-Lactam-Responsive vs. Non-Responsive Strains

Methicillin-resistant Staphylococcus aureus (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:	Selvi C. Ersoy, Blake M. Hanson, Richard A. Proctor, Cesar A. Arias, Truc T. Tran, Henry F. Chambers, Arnold S. Bayer
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) β-lactam susceptibility sodium bicarbonate (NaHCO<sub>3</sub>) RNA-sequencing (RNA-seq) Genetics QH426-470
Acceso en línea:	https://doaj.org/article/3a0d850746cb45ea808e50bf8ec72ec5
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spelling	oai:doaj.org-article:3a0d850746cb45ea808e50bf8ec72ec52021-11-25T17:40:12ZImpact of Bicarbonate-β-Lactam Exposures on Methicillin-Resistant <i>Staphylococcus aureus</i> (MRSA) Gene Expression in Bicarbonate-β-Lactam-Responsive vs. Non-Responsive Strains10.3390/genes121116502073-4425https://doaj.org/article/3a0d850746cb45ea808e50bf8ec72ec52021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1650https://doaj.org/toc/2073-4425Methicillin-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.Selvi C. ErsoyBlake M. HansonRichard A. ProctorCesar A. AriasTruc T. TranHenry F. ChambersArnold S. BayerMDPI AGarticleMethicillin-resistant <i>Staphylococcus aureus</i> (MRSA)β-lactam susceptibilitysodium bicarbonate (NaHCO<sub>3</sub>)RNA-sequencing (RNA-seq)GeneticsQH426-470ENGenes, Vol 12, Iss 1650, p 1650 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) β-lactam susceptibility sodium bicarbonate (NaHCO<sub>3</sub>) RNA-sequencing (RNA-seq) Genetics QH426-470
spellingShingle	Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) β-lactam susceptibility sodium bicarbonate (NaHCO<sub>3</sub>) RNA-sequencing (RNA-seq) Genetics QH426-470 Selvi C. Ersoy Blake M. Hanson Richard A. Proctor Cesar A. Arias Truc T. Tran Henry F. Chambers Arnold S. Bayer 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
description	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.
format	article
author	Selvi C. Ersoy Blake M. Hanson Richard A. Proctor Cesar A. Arias Truc T. Tran Henry F. Chambers Arnold S. Bayer
author_facet	Selvi C. Ersoy Blake M. Hanson Richard A. Proctor Cesar A. Arias Truc T. Tran Henry F. Chambers Arnold S. Bayer
author_sort	Selvi C. Ersoy
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/3a0d850746cb45ea808e50bf8ec72ec5
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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

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