{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T05:04:48Z","timestamp":1789707888080,"version":"4.0.1"},"reference-count":98,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/CAL-EST\/30713\/2017"],"award-info":[{"award-number":["PTDC\/CAL-EST\/30713\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/04413\/2025"],"award-info":[{"award-number":["UID\/04413\/2025"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["LA\/P\/0117\/2020"],"award-info":[{"award-number":["LA\/P\/0117\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["2022.07931.PTDC"],"award-info":[{"award-number":["2022.07931.PTDC"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["2021.05063.BD"],"award-info":[{"award-number":["2021.05063.BD"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"\n Multidrug efflux pumps (MDR EPs) play a major role in the emergence of antimicrobial resistance in\n Staphylococcus aureus<\/jats:italic>\n . Among these, the native NorA is the most well-studied MDR EP in this species. However, efflux-mediated resistance is only scarcely characterized in other staphylococci. The aims of this study were to assess the genetic variability and phylogenetic relations of main efflux pump genes in\n S. aureus<\/jats:italic>\n and four other pathogenic staphylococci, and to identify new putative MDR transporters in these species. Nucleotide sequences of\n norA<\/jats:italic>\n ,\n norB<\/jats:italic>\n ,\n norC<\/jats:italic>\n ,\n norB\/C<\/jats:italic>\n ,\n mepA<\/jats:italic>\n and related sequences of\n S. aureus<\/jats:italic>\n ,\n Staphylococcus epidermidis<\/jats:italic>\n ,\n Staphylococcus haemolyticus<\/jats:italic>\n ,\n Staphylococcus lugdunensis<\/jats:italic>\n and\n Staphylococcus hominis<\/jats:italic>\n were compiled and assessed for gene variability. The\n norA<\/jats:italic>\n variability was further evaluated in a collection of clinical strains of\n S. epidermidis<\/jats:italic>\n ,\n S. haemolyticus<\/jats:italic>\n and\n S. hominis<\/jats:italic>\n . Phylogenetic analyses were performed to characterize the evolution of\n norA<\/jats:italic>\n across the five species and to explore potential relations between\n norB<\/jats:italic>\n ,\n norC<\/jats:italic>\n ,\n norB\/C<\/jats:italic>\n and related sequences. Additional putative MDR transporter genes were searched in public databases and then BLAST searched against complete genomes of each species. Only\n S. aureus<\/jats:italic>\n presented several\n norA<\/jats:italic>\n and\n norB<\/jats:italic>\n alleles. The relations between the\n norA<\/jats:italic>\n genes of the five species follow the evolutionary relations of these staphylococci. Phylogenetic analysis also revealed the existence of a\n norB\/C<\/jats:italic>\n gene in\n S. aureus<\/jats:italic>\n , which is homologous to the\n norB\/C<\/jats:italic>\n genes of\n S. epidermidis<\/jats:italic>\n ,\n S. haemolyticus<\/jats:italic>\n ,\n S. lugdunensis<\/jats:italic>\n and\n S. hominis<\/jats:italic>\n . It also indicated that\n S. aureus norB<\/jats:italic>\n and\n norC<\/jats:italic>\n as well as the newly assigned\n S. haemolyticus norB\/C-like<\/jats:italic>\n are related genes, absent in the other species.\n In silico<\/jats:italic>\n analysis identified several new candidate MDR transporters in the five species. This study provides a novel, comprehensive comparative analysis of major efflux pump determinants across five clinically relevant\n Staphylococcus<\/jats:italic>\n species. This analysis expanded our knowledge of the\n norA<\/jats:italic>\n evolutionary pathways and provided a framework for a more consistent annotation of\n norB<\/jats:italic>\n ,\n norC<\/jats:italic>\n and related determinants among these staphylococci. The identification of putatively new MDR transporter determinants in staphylococcal species of clinical relevance other than\n S. aureus<\/jats:italic>\n provides a framework for future functional studies.\n <\/jats:p>","DOI":"10.3389\/fphar.2026.1870078","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:36:20Z","timestamp":1789706180000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Occurrence, variability and evolutionary relations of efflux pump determinants across five pathogenic Staphylococcus species"],"prefix":"10.3389","volume":"17","author":[{"given":"Carolina","family":"Ferreira","sequence":"first","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa","place":["Lisbon, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Martinho","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa","place":["Lisbon, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Parreira","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa","place":["Lisbon, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9","family":"Melo-Cristino","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Microbiologia, Servi\u00e7o de Patologia Cl\u00ednica, Centro Hospitalar Universit\u00e1rio Lisboa Norte","place":["Lisboa, Portugal"]},{"name":"Instituto de Microbiologia, Faculdade de Medicina, Universidade de Lisboa","place":["Lisbon, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Viveiros","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa","place":["Lisbon, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia Santos","family":"Costa","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa","place":["Lisbon, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Couto","sequence":"additional","affiliation":[{"name":"Global Health and Tropical Medicine, GHTM, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa","place":["Lisbon, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"W39","DOI":"10.1093\/nar\/gkv416","article-title":"The MEME suite","volume":"43","author":"Bailey","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1080\/14787210.2020.1730813","article-title":"Emergence of coagulase-negative staphylococci","volume":"18","author":"Becker","year":"2020","journal-title":"Expert Rev. anti-infect. 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