{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T16:15:58Z","timestamp":1789402558431,"version":"build-2803163510"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:p><jats:italic>Staphylococcus aureus<\/jats:italic> is part of normal human flora and is widely associated with hospital-acquired bacteremia. <jats:italic>S. aureus<\/jats:italic> has shown a diverse array of resistance to environmental stresses and antibiotics. Methicillin-resistant <jats:italic>S. aureus<\/jats:italic> (MRSA) is on the high priority list of new antibiotics discovery and glycopeptides are considered the last drug of choice against MRSA. <jats:italic>S. aureus<\/jats:italic> has developed resistance against glycopeptides and the emergence of vancomycin-intermediate-resistant, vancomycin-resistant, and teicoplanin-resistant strains is globally reported. Teicoplanin-associated genes tcaR-tcaA-tcaB (tcaRAB) is known as the <jats:italic>S. aureus<\/jats:italic> glycopeptide resistance operon that is associated with glycopeptide resistance. Here, for the first time, the role of tcaRAB in <jats:italic>S. aureus<\/jats:italic> persister cells formation, and \u0394tcaA dependent persisters\u2019 ability to resuscitate the bacterial population was explored. We recovered a clinical strain of MRSA from a COVID-19 patient which showed a high level of resistance to teicoplanin, vancomycin, and methicillin. Whole genome RNA sequencing revealed that the tcaRAB operon expression was altered followed by high expression of <jats:italic>glyS<\/jats:italic> and <jats:italic>sgtB<\/jats:italic>. The RNA-seq data revealed a significant decrease in <jats:italic>tcaA<\/jats:italic> (<jats:italic>p<\/jats:italic> =\u20090.008) and <jats:italic>tcaB<\/jats:italic> (<jats:italic>p<\/jats:italic> =\u20090.04) expression while <jats:italic>tcaR<\/jats:italic> was not significantly altered. We knocked down <jats:italic>tcaA<\/jats:italic>, <jats:italic>tcaB<\/jats:italic>, and <jats:italic>tcaR<\/jats:italic> using CRISPR-dCas9 and the results showed that when <jats:italic>tcaA<\/jats:italic> was suppressed by dCas9, a significant increase was witnessed in persister cells while <jats:italic>tcaB<\/jats:italic> suppression did not induce persistence. The results were further evaluated by creating a <jats:italic>tcaA<\/jats:italic> mutant that showed \u0394tcaA formed a significant increase in persisters in comparison to the wild type. Based on our findings, we concluded that <jats:italic>tcaA<\/jats:italic> is the gene that increases persister cells and glycopeptide resistance and could be a potential therapeutic target in <jats:italic>S. aureus<\/jats:italic>.<\/jats:p>","DOI":"10.3389\/fmicb.2023.1241995","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T07:15:44Z","timestamp":1697181344000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["Teicoplanin associated gene tcaA inactivation increases persister cell formation in Staphylococcus aureus"],"prefix":"10.3389","volume":"14","author":[{"given":"Gul","family":"Habib","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haji","family":"Gul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prevez","family":"Ahmad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azam","family":"Hayat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mujaddad Ur","family":"Rehman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihab","family":"Mohamed Moussa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hosam O.","family":"Elansary","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/npre.2010.4282.2","article-title":"Differential expression analysis for sequence count data","author":"Anders","year":"2010","journal-title":"Nat. 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