{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:22:41Z","timestamp":1790403761781,"version":"4.1.0"},"reference-count":18,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T00:00:00Z","timestamp":1559260800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>One of the most interesting features of Staphylococcus aureus is its ability to switch to a small colony variant (SCV). This switch allows the pathogen to survive periods of antibiotic treatment or pressure from the immune system of the host and further enables it to start the infection once again after the environmental stress declines. However, so far only little is known about this reversion back to the more virulent wild type phenotype. Therefore, this study aimed to analyze the frequency of reversion to the wild type phenotype of thymidine auxotroph S. aureus SCV isolates (TD-SCVs) obtained from patients with cystic fibrosis (CF). With the use of single cell starting cultures, the occurrence of the thymidine prototroph revertants was monitored. The underlying mutational cause of the SCVs and subsequent revertants were analyzed by sequencing the gene coding for thymidylate synthase (ThyA), whose mutations are known to produce thymidine auxotroph S. aureus SCV. In our study, the underlying mutational cause for the switch to the TD-SCV phenotype was primarily point mutations. Out of twelve isolates, seven isolates showed an occurrence of revertants with a frequency ranging from 90.06% to 0.16%. This high variability in the frequency of reversion to the wild type was not expected. However, this variability in the frequency of reversion may also be the key to successful re-infection of the host. Sometimes quick reversion to the wild type proves necessary for survival, whereas other times, staying hidden for a bit longer leads to success in re-colonization of the host.<\/jats:p>","DOI":"10.3390\/ijerph16111940","type":"journal-article","created":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T11:59:56Z","timestamp":1559303996000},"page":"1940","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Phenotypic Stability of Staphylococcus aureus Small Colony Variants (SCV) Isolates from Cystic Fibrosis (CF) Patients"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8472-2155","authenticated-orcid":false,"given":"Clemens","family":"Kittinger","sequence":"first","affiliation":[{"name":"Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4859-4867","authenticated-orcid":false,"given":"Daniela","family":"Toplitsch","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Folli","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilian","family":"Masoud Landgraf","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1592-4559","authenticated-orcid":false,"given":"Gernot","family":"Zarfel","sequence":"additional","affiliation":[{"name":"Diagnostic and Research Center for Molecular BioMedicine, Medical University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.ijmm.2013.09.012","article-title":"Extended Staphylococcus Aureus Persistence in Cystic Fibrosis is Associated with Bacterial Adaptation","volume":"303","author":"Hirschhausen","year":"2013","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"15","DOI":"10.4137\/MBI.S25800","article-title":"Phenotypic and Genotypic Characteristics of Small Colony Variants and their Role in Chronic Infection","volume":"8","author":"Johns","year":"2015","journal-title":"Microbiol. Insights"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1007\/s00284-016-0994-z","article-title":"Analysis and Characterization of Staphylococcus Aureus Small Colony Variants Isolated from Cystic Fibrosis Patients in Austria","volume":"72","author":"Zarfel","year":"2016","journal-title":"Curr. Microbiol."},{"key":"ref_4","first-page":"515","article-title":"Small Colony Variants (SCVs) of Staphylococcus Aureus\u2014A Bacterial Survival Strategy","volume":"12","author":"Kahl","year":"2013","journal-title":"Infect. Genet. Evol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"548","DOI":"10.1007\/s12223-010-0089-3","article-title":"Small Colony Variants of Staphylococcus Aureus\u2014Review","volume":"55","author":"Melter","year":"2010","journal-title":"Folia Microbiol. (Praha)"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"7265","DOI":"10.1128\/AAC.00742-15","article-title":"Thymidine-Dependent Staphylococcus Aureus Small-Colony Variants are Induced by Trimethoprim-Sulfamethoxazole (SXT) and have Increased Fitness during SXT Challenge","volume":"59","author":"Kriegeskorte","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1128\/JB.00912-07","article-title":"In Vivo Mutations of Thymidylate Synthase (Encoded by thyA) are Responsible for Thymidine Dependency in Clinical Small-Colony Variants of Staphylococcus Aureus","volume":"190","author":"Chatterjee","year":"2008","journal-title":"J. Bacteriol."},{"key":"ref_8","first-page":"33","article-title":"Staphylococcus Aureus Small Colony Variants (SCVs) and their Role in Disease. Anim","volume":"12","author":"Atalla","year":"2011","journal-title":"Health Res. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1093\/cid\/cit270","article-title":"Staphylococcus Aureus Small-Colony Variants are Independently Associated with Worse Lung Disease in Children with Cystic Fibrosis","volume":"57","author":"Wolter","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1128\/IAI.01487-13","article-title":"Identification of Point Mutations in Clinical Staphylococcus Aureus Strains that Produce Small-Colony Variants Auxotrophic for Menadione","volume":"82","author":"Dean","year":"2014","journal-title":"Infect. Immun."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Lannergard, J., Cao, S., Norstrom, T., Delgado, A., Gustafson, J.E., and Hughes, D. (2011). Genetic Complexity of Fusidic Acid-Resistant Small Colony Variants (SCV) in Staphylococcus Aureus. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028366"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1128\/JCM.01170-11","article-title":"Thymidine Auxotrophic Staphylococcus Aureus Small-Colony Variant Endocarditis and Left Ventricular Assist Device Infection","volume":"50","author":"Seville","year":"2012","journal-title":"J. Clin. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3146","DOI":"10.1128\/JCM.00132-07","article-title":"Emergence of an Epidemic Clone of Community-Associated Methicillin-Resistant Panton-Valentine Leucocidin-Negative Staphylococcus Aureus in Cystic Fibrosis Patient Populations","volume":"45","author":"Campana","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.ijmm.2010.08.002","article-title":"Impact of Staphylococcus Aureus on the Pathogenesis of Chronic Cystic Fibrosis Lung Disease","volume":"300","author":"Kahl","year":"2010","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1093\/clinids\/20.1.95","article-title":"Persistent and Relapsing Infections Associated with Small-Colony Variants of Staphylococcus Aureus","volume":"20","author":"Proctor","year":"1995","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2183","DOI":"10.1128\/AAC.01395-07","article-title":"The Thymidine-Dependent Small-Colony-Variant Phenotype is Associated with Hypermutability and Antibiotic Resistance in Clinical Staphylococcus Aureus Isolates","volume":"52","author":"Besier","year":"2008","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/emmm.201000115","article-title":"Staphylococcus Aureus Phenotype Switching: An Effective Bacterial Strategy to Escape Host Immune Response and Establish a Chronic Infection","volume":"3","author":"Tuchscherr","year":"2011","journal-title":"EMBO Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3221","DOI":"10.1128\/AEM.07307-11","article-title":"Microbial Scout Hypothesis, Stochastic Exit from Dormancy, and the Nature of Slow Growers","volume":"78","author":"Buerger","year":"2012","journal-title":"Appl. Environ. Microbiol."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/11\/1940\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:55:11Z","timestamp":1760187311000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/11\/1940"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,31]]},"references-count":18,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,6]]}},"alternative-id":["ijerph16111940"],"URL":"https:\/\/doi.org\/10.3390\/ijerph16111940","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,31]]}}}