{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:21:26Z","timestamp":1790727686956,"version":"4.1.0"},"reference-count":23,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T00:00:00Z","timestamp":1568764800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T00:00:00Z","timestamp":1568764800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013115","name":"Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents","doi-asserted-by":"crossref","award":["[2012]241"],"award-info":[{"award-number":["[2012]241"]}],"id":[{"id":"10.13039\/501100013115","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Microbiol"],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n              <jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>We aimed to determine the evolutionary pathways of rifampicin resistance in <jats:italic>Staphylococcus aureus<\/jats:italic>, and the impact of resistance mutations in the <jats:italic>rpoB<\/jats:italic> gene on fitness.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Three clinical strains and one reference strain were used to select for rifampicin-resistant <jats:italic>S. aureus<\/jats:italic> variants. The mutations responsible for rifampicin resistance in all of the selected isolates in vitro were investigated by polymerase chain reaction (PCR) and DNA sequencing. To compare the fitness cost of <jats:italic>rpoB<\/jats:italic> mutations against their corresponding original isolates, we performed bacterial growth curve assays, static biofilm assays, in vitro competition experiments and an infection model of <jats:italic>Galleria mellonella<\/jats:italic> larvae.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>We obtained four rifampicin-resistant <jats:italic>S. aureus<\/jats:italic> isolates that showed high levels of resistance to rifampicin with a minimal inhibitory concentration (MIC) of 128\u2009mg\/L, and all isolates had a mutation at position 481 (H481F\/Y) in RpoB. A broth microdilution assay indicated that mutation of H481F\/Y did not affect susceptibility to common antibacterial drugs but slightly increased the vancomycin MIC. To identify the pathways involved in the development of rifampicin resistance, 32 variants (eight mutants for each strain) and four original isolates were selected for gene sequencing. Different generations of isolates were found to harbor various mutations sites. Compared with the corresponding original isolates, an in vitro fitness assay of the variant isolates showed that growth and virulence were reduced, with a statistically significantly decreased fitness, whereas the capacity for biofilm formation was elevated.<\/jats:p>\n              <\/jats:sec>\n              <jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings suggested that the acquisition of rifampicin resistance in <jats:italic>S. aureus<\/jats:italic> was dynamic and was associated with a significant fitness cost.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12866-019-1573-9","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T12:05:21Z","timestamp":1568808321000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Evolution of resistance mechanisms and biological characteristics of rifampicin-resistant Staphylococcus aureus strains selected in vitro"],"prefix":"10.1186","volume":"19","author":[{"given":"Chong","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renchi","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beibei","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuebin","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiucai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangkuo","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guofeng","family":"Dong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianming","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2171-4710","authenticated-orcid":false,"given":"Tieli","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,9,18]]},"reference":[{"key":"1573_CR1","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1128\/JB.00261-16","volume":"198","author":"M Villanueva","year":"2016","unstructured":"Villanueva M, Jousselin A, Baek KT, Prados J, Andrey DO, Renzoni A, et al. 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