{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T06:22:41Z","timestamp":1788675761267,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,26]],"date-time":"2024-08-26T00:00:00Z","timestamp":1724630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) Germany\u2019s Excellence Strategy\u2014EXC 2124\u2014390838134 \u2018Controlling Microbes to Fight Infections\u2019","doi-asserted-by":"publisher","award":["BB\/W013630\/1"],"award-info":[{"award-number":["BB\/W013630\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fund of University of T\u00fcbingen","award":["BB\/W013630\/1"],"award-info":[{"award-number":["BB\/W013630\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Bicarbonate and CO2 are essential substrates for carboxylation reactions in bacterial central metabolism. In Staphylococcus aureus, the bicarbonate transporter, MpsABC (membrane potential-generating system) is the only carbon concentrating system. An mpsABC deletion mutant can hardly grow in ambient air. In this study, we investigated the changes that occur in S. aureus when it suffers from CO2\/bicarbonate deficiency. Electron microscopy revealed that \u0394mpsABC has a twofold thicker cell wall thickness compared to the parent strain. The mutant was also substantially inert to cell lysis induced by lysostaphin and the non-ionic surfactant Triton X-100. Mass spectrometry analysis of muropeptides revealed the incorporation of alanine into the pentaglycine interpeptide bridge, which explains the mutant\u2019s lysostaphin resistance. Flow cytometry analysis of wall teichoic acid (WTA) glycosylation patterns revealed a significantly lower \u03b1-glycosylated and higher \u00df-glycosylated WTA, explaining the mutant\u2019s increased resistance towards Triton X-100. Comparative transcriptome analysis showed altered gene expression profiles. Autolysin-encoding genes such as sceD, a lytic transglycosylase encoding gene, were upregulated, like in vancomycin-intermediate S. aureus mutants (VISA). Genes related to cell wall-anchored proteins, secreted proteins, transporters, and toxins were downregulated. Overall, we demonstrate that bicarbonate deficiency is a stress response that causes changes in cell wall composition and global gene expression resulting in increased resilience to cell wall lytic enzymes and detergents.<\/jats:p>","DOI":"10.3390\/ijms25179251","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T09:26:51Z","timestamp":1724750811000},"page":"9251","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Staphylococcus aureus Stress Response to Bicarbonate Depletion"],"prefix":"10.3390","volume":"25","author":[{"given":"Elisa","family":"Liberini","sequence":"first","affiliation":[{"name":"Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine T\u00fcbingen (IMIT), University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0556-238X","authenticated-orcid":false,"given":"Sook-Ha","family":"Fan","sequence":"additional","affiliation":[{"name":"Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine T\u00fcbingen (IMIT), University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"The Lundquist Institute, Torrance, CA 90502, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1968-0192","authenticated-orcid":false,"given":"Arnold S.","family":"Bayer","sequence":"additional","affiliation":[{"name":"The Lundquist Institute, Torrance, CA 90502, USA"},{"name":"David Geffen School of Medicine at UCLA\u2013University of California, Los Angeles, CA 90095, 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Infectious Diseases, Faculty of Medicine, Geneva University Hospitals, 1205 Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joe","family":"Gray","sequence":"additional","affiliation":[{"name":"Biosciences Institute, Centre for Bacterial Cell Biology, Newcastle University, Newcastle upon Tyne NE1 7RU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharina","family":"Hipp","sequence":"additional","affiliation":[{"name":"Electron Microscopy Facility, Max-Planck-Institute for Biology, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iris","family":"Koch","sequence":"additional","affiliation":[{"name":"Electron Microscopy Facility, Max-Planck-Institute for Biology, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3209-8626","authenticated-orcid":false,"given":"Andreas","family":"Peschel","sequence":"additional","affiliation":[{"name":"Department of Infection Biology, Interfaculty Institute of Microbiology and Infection Medicine T\u00fcbingen (IMIT), University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"},{"name":"Excellence Cluster 2124 \u2018Controlling Microbes to Fight Infections\u2019 (CMFI), University of T\u00fcbingen, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Sailer","sequence":"additional","affiliation":[{"name":"Electron Microscopy Facility, Max-Planck-Institute for Biology, 72076 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Vollmer","sequence":"additional","affiliation":[{"name":"Biosciences Institute, Centre for Bacterial Cell Biology, Newcastle 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