{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:33:08Z","timestamp":1790425988909,"version":"4.1.0"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T00:00:00Z","timestamp":1649808000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Microbiol"],"published-print":{"date-parts":[[2022,12]]},"abstract":"Abstract<\/jats:title>\n Background<\/jats:title>\n Chlorhexidine gluconate (CHG) is a disinfectant agent with different applications in health care. Improper use of CHG causes antimicrobial resistance in bacteria as a public health threat. Since Staphylococcus aureus<\/jats:italic> is a common bacteria, it is expected usually exposed to CHG in the hospital and community. The present study aimed to correlate the phenotypic and genotypic changes in a S. aureus<\/jats:italic> strain upon serial adaptation with supra-inhibitory CHG concentration for 50\u00a0days.<\/jats:p>\n <\/jats:sec>\n Results<\/jats:title>\n After in vitro serial culture of 5\u2009\u00d7\u2009105<\/jats:sup>\u00a0CFU\/ml of a clinical vancomycin-susceptible S. aureus<\/jats:italic> strain (VAN-S) into brain heart infusion (BHI) broth containing CHG 1\/4, 1\/2, 1, and 2\u2009\u00d7\u2009minimal inhibitory concentration (MIC) values of VAN-S in 37\u00a0\u00b0C during 50\u00a0days, we isolated a S. aureus<\/jats:italic> strain (CHGVan-I<\/jats:sub>) with a\u2009\u2265\u2009twofold decrease in susceptibility to CHG and vancomycin. CHG-induced CHGVan-I<\/jats:sub> strain was considered as a vancomycin-intermediate S. aureus<\/jats:italic> (VISA) strain with a VAN MIC of 4\u00a0\u03bcg\/ml using the broth macro dilution method. However, reduced resistance was observed to tetracycline family antibiotics (doxycycline and tetracycline) using a modified Kirby-Bauer disk diffusion test. Moreover, a remarkable reduction was detected in growth rate, hemolysis activity (the lysis of human red blood cells by alpha-hemolysin), and colony pigmentation (on BHI agar plates). Biofilm formation (using the Microtiter plate method and crystal violet staining) was significantly increased upon CHG treatment. Adaptive changes in the expression of a set of common genes related to the development of VISA phenotype (gra<\/jats:italic>TSR, vra<\/jats:italic>TSR, wal<\/jats:italic>KR, agr<\/jats:italic> RNAIII, sce<\/jats:italic>D, pbp<\/jats:italic>B, and fmt<\/jats:italic>A) were analyzed by Reverse Transcription quantitative PCR (RT-qPCR) experiment. Significant changes in vra<\/jats:italic>TSR, agr<\/jats:italic> RNAIII, sce<\/jats:italic>D, and pbp<\/jats:italic>B expression were observed. However, gene sequencing of the two-component system vra<\/jats:italic>TSR using the Sanger sequencing method did not detect any non-synonymous substitution in CHGVan-I<\/jats:sub> compared to wild-type. The clonality of VAN-S and CHGVan-I<\/jats:sub> strains was verified using the pulsed-field gel electrophoresis (PFGE) method.<\/jats:p>\n <\/jats:sec>\n Conclusions<\/jats:title>\n The importance of the present study should be stated in new detected mechanisms underlying VISA development. We found a link between the improper CHX use and the development of phenotypic and genotypic features, typical of VISA clinical isolates, in a CHG-induced strain.<\/jats:p>\n Since disruption of the cell wall biosynthesis occurs in VISA isolates, our CHG-induced VISA strain proved new insights into the role of CHG in the stimulation of the S. aureus<\/jats:italic> cell wall.<\/jats:p>\n <\/jats:sec>","DOI":"10.1186\/s12866-022-02522-0","type":"journal-article","created":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T08:03:12Z","timestamp":1649836992000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Phenotypic and genotypic changes of Staphylococcus aureus in the presence of the inappropriate concentration of chlorhexidine gluconate"],"prefix":"10.1186","volume":"22","author":[{"given":"Neda","family":"Baseri","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shahin","family":"Najar-Peerayeh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bita","family":"Bakhshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floriana","family":"Campanile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,13]]},"reference":[{"key":"2522_CR1","unstructured":"Lunestad BT, M\u00f8retr\u00f8 T, Hegstad K, Langsrud S, Scheie AA, Kapperud G, et al. 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All methods were carried out in accordance with relevant guidelines and regulations. The wild-type VAN-S strain was obtained from a patient (in Motahhari Hospital, Tehran, Iran) with an informed consent. For alpha-hemolysis analysis, the whole blood was obtained from a healthy volunteer with an informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors have no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"100"}}