{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:36:42Z","timestamp":1785429402347,"version":"3.56.0"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T00:00:00Z","timestamp":1772496000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2026,3,3]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n The presence of heterogeneous vancomycin-intermediate\n Staphylococcus aureus<\/jats:italic>\n (hVISA) among methicillin-resistant\n Staphylococcus aureus<\/jats:italic>\n (MRSA) strains has been associated with vancomycin treatment failure, especially in cases of MRSA pneumonia. This study aimed to analyze the molecular characteristics and risk factors for hVISA among MRSA strains isolated from pneumonia patients and to validate the most important risk factors. All the MRSA clinical isolates were collected in a multicenter, prospective, observational clinical trial from July 2012 to June 2020. The hVISA strains were verified via a modified population analysis profile\u2013area under the curve method, and the prevalence of hVISA in hospitalized pneumonia patients was 53.5% (61\/114). Sequence type 5 (ST5)-MRSA, the dominant hVISA strain, and ST764-MRSA, the dominant vancomycin-susceptible\n S. aureus<\/jats:italic>\n (VSSA) strain, exhibited comparable incidences (27.2% vs 36.8%) but with different hVISA detection rates (90.3% vs 21.4%,\n P<\/jats:italic>\n < 0.001). Furthermore, the efflux pump gene\n qacA<\/jats:italic>\n was identified by multivariate logistic regression analysis as an independent significant predictor of hVISA occurrence in ST5-MRSA (\n P<\/jats:italic>\n < 0.001). This association was confirmed when both the recipient ST5-MRSA and ST764-MRSA strains that acquired the\n qacA<\/jats:italic>\n -borne plasmid exhibited phenotypic transformation from VSSA to hVISA. This study provides evidence that the acquisition of\n qacA<\/jats:italic>\n by the VSSA strain is associated with the formation of hVISA in MRSA isolates from hospitalized pneumonia patients.\n <\/jats:p>\n <\/jats:sec>\n \n IMPORTANCE<\/jats:title>\n \n Methicillin-resistant\n Staphylococcus aureus<\/jats:italic>\n (MRSA) is among the leading causes of pulmonary infections, and currently, vancomycin use remains an effective intervention. The irrational use of vancomycin has increased the prevalence of heterogeneous vancomycin-intermediate\n Staphylococcus aureus<\/jats:italic>\n (hVISA)\/vancomycin-intermediate\n S. aureus<\/jats:italic>\n strains in pneumonia patients infected with MRSA, but the underlying molecular characteristics remain unknown. This study focused on the evidently high detection rates of hVISA strains from pneumonia patients from a prospective observational study in China and investigated the predictive risk factors for the dominant hVISA strain sequence type 5 (ST5)-MRSA. Multivariate logistic regression analysis of variables identified as significant for host, pathogen, and genetic characteristics revealed that qacA was a significant independent predictor of the development of hVISA in ST5-MRSA, which was confirmed by plasmid-based experiments. This study provides new insights and an improved understanding of the decreased vancomycin susceptibility of MRSA in pneumonia patients and provides evidence-based support for optimizing clinical treatment plans from an innovative perspective to maintain the efficacy of vancomycin.\n <\/jats:p>\n <\/jats:sec>\n \n CLINICAL TRIALS<\/jats:title>\n \n This study is registered with the China Clinical Trials Registry as\n ChiCTR-OPC-16007920<\/jats:related-object>\n and\n ChiCTR-OPC-17012567<\/jats:related-object>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1128\/spectrum.01963-25","type":"journal-article","created":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T14:00:44Z","timestamp":1770040844000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["qacA<\/i>\n is a key factor in heteroresistance to vancomycin in sequence type 5 methicillin-resistant\n Staphylococcus aureus<\/i>\n isolates from pneumonia patients"],"prefix":"10.1128","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0001-9269","authenticated-orcid":false,"given":"Kaiting","family":"Zhang","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Antibiotics, Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission & National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0353-1697","authenticated-orcid":false,"given":"Lin","family":"Xi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013q1eq08","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Antibiotics, Key Laboratory of Clinical Pharmacology of Antibiotics, National Population and Family Planning Commission & National 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