{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T14:36:44Z","timestamp":1774795004889,"version":"3.50.1"},"reference-count":90,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T00:00:00Z","timestamp":1626134400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"crossref","award":["AI121860"],"award-info":[{"award-number":["AI121860"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Antimicrobial Resistance and Therapeutic Discovery Training Program","award":["NIAID T32 award AI106699-05"],"award-info":[{"award-number":["NIAID T32 award AI106699-05"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    Vancomycin-intermediate\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (VISA) typically arises through accumulation of chromosomal mutations that alter cell-wall thickness and global regulatory pathways. Genome-based prediction of VISA requires understanding whether strain background influences patterns of mutation that lead to resistance. We used an iterative method to experimentally evolve three important methicillin-resistant\n                    <jats:italic>S. aureus<\/jats:italic>\n                    (MRSA) strain backgrounds\u2014(CC1, CC5 and CC8 (USA300)) to generate a library of 120 laboratory selected VISA isolates. At the endpoint, isolates had vancomycin MICs ranging from 4 to 10 \u03bcg\/mL. We detected mutations in more than 150 genes, but only six genes (already known to be associated with VISA from prior studies) were mutated in all three background strains (\n                    <jats:italic>walK, prs, rpoB, rpoC, vraS, yvqF<\/jats:italic>\n                    ). We found evidence of interactions between loci (e.g.,\n                    <jats:italic>vraS<\/jats:italic>\n                    and\n                    <jats:italic>yvqF<\/jats:italic>\n                    mutants were significantly negatively correlated) and\n                    <jats:italic>rpoB, rpoC, vraS<\/jats:italic>\n                    and\n                    <jats:italic>yvqF<\/jats:italic>\n                    were more frequently mutated in one of the backgrounds. Increasing vancomycin resistance was correlated with lower maximal growth rates (a proxy for fitness) regardless of background. However, CC5 VISA isolates had higher MICs with fewer rounds of selection and had lower fitness costs than the CC8 VISA isolates. Using multivariable regression, we found that genes differed in their contribution to overall MIC depending on the background. Overall, these results demonstrated that VISA evolved through mutations in a similar set of loci in all backgrounds, but the effect of mutation in common genes differed with regard to fitness and contribution to resistance in different strains.\n                  <\/jats:p>","DOI":"10.7717\/peerj.11764","type":"journal-article","created":{"date-parts":[[2021,7,13]],"date-time":"2021-07-13T03:06:09Z","timestamp":1626145569000},"page":"e11764","source":"Crossref","is-referenced-by-count":18,"title":["Effect of genetic background on the evolution of Vancomycin-Intermediate\n                    <i>Staphylococcus aureus<\/i>\n                    (VISA)"],"prefix":"10.7717","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3212-2120","authenticated-orcid":true,"given":"Michelle","family":"Su","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle H.","family":"Davis","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Peterson","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9789-8915","authenticated-orcid":true,"given":"Claudia","family":"Solis-Lemus","sequence":"additional","affiliation":[{"name":"Wisconsin Institute for Discovery and Department of Plant Pathology, University of Wisconsin-Madison, Madison, Wisconsin, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah W.","family":"Satola","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8966-9680","authenticated-orcid":true,"given":"Timothy D.","family":"Read","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, School of Medicine, Emory University, Atlanta, Georgia, USA"},{"name":"Department of Dermatology, School of Medicine, Emory University, Atlanta, Georgia, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"4443","published-online":{"date-parts":[[2021,7,13]]},"reference":[{"issue":"3","key":"10.7717\/peerj.11764\/ref-1","doi-asserted-by":"publisher","first-page":"e00444-16","DOI":"10.1128\/mBio.00444-16","article-title":"Whole-genome sequencing for routine pathogen surveillance in public health: a population 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