{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T06:23:02Z","timestamp":1790403782457,"version":"4.1.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T00:00:00Z","timestamp":1591920000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"DOI":"10.3389\/fmicb.2020.01300","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T08:09:19Z","timestamp":1591949359000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Spontaneously Occurring Small-Colony Variants of Staphylococcus aureus Show Enhanced Clearance by THP-1 Macrophages"],"prefix":"10.3389","volume":"11","author":[{"given":"Simon M.","family":"Stoneham","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daire M.","family":"Cantillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"Waddell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin J.","family":"Llewelyn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,6,12]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1128\/aac.50.3.841-851.2006","article-title":"Pharmacodynamic evaluation of the intracellular activities of antibiotics against Staphylococcus aureus in a model of THP-1 macrophages.","volume":"50","author":"Barcia-Macay","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"B2","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1128\/jcm.01510-06","article-title":"Prevalence and clinical significance of Staphylococcus aureus small-colony variants in cystic fibrosis lung disease.","volume":"45","author":"Besier","year":"2007","journal-title":"J. Clin. Microbiol."},{"key":"B3","year":"2012","journal-title":"M07\u2013A9. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard\u2014Ninth Edition. CLSI document M07\u2013A9."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008668","article-title":"The identification of markers of macrophage differentiation in PMA-stimulated THP-1 cells and monocyte-derived macrophages.","volume":"5","author":"Daigneault","year":"2010","journal-title":"PLoS One"},{"key":"B5","doi-asserted-by":"publisher","first-page":"5404","DOI":"10.1128\/jb.00948-12","article-title":"Phenotype switching is a natural consequence of Staphylococcus aureus replication.","volume":"194","author":"Edwards","year":"2012","journal-title":"J. Bacteriol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1111\/cmi.12485","article-title":"Inability to sustain intraphagolysosomal killing of Staphylococcus aureus predisposes to bacterial persistence in macrophages.","volume":"18","author":"Jubrail","year":"2016","journal-title":"Cell Microbiol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/j.jinf.2013.10.015","article-title":"Staphylococcus aureus bloodstream infection: a pooled analysis of five prospective, observational studies.","volume":"68","author":"Kaasch","year":"2014","journal-title":"J. Infect."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1086\/515238","article-title":"Persistent infection with small colony variant strains of Staphylococcus aureus in patients with cystic fibrosis.","volume":"177","author":"Kahl","year":"1998","journal-title":"J. Infect. Dis."},{"key":"B9","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1128\/cmr.00069-15","article-title":"clinical significance and pathogenesis of staphylococcal small colony variants in persistent infections.","volume":"29","author":"Kahl","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1038","DOI":"10.1016\/j.ijmm.2014.07.013","article-title":"Staphylococcus aureus isolates from chronic osteomyelitis are characterized by high host cell invasion and intracellular adaptation, but still induce inflammation.","volume":"304","author":"Kalinka","year":"2014","journal-title":"Int. J. Med. Microbiol."},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00119-19","article-title":"Alternative enzyme protection assay to overcome the drawbacks of the gentamicin protection assay for measuring entry and intracellular survival of staphylococci.","volume":"87","author":"Kim","year":"2019","journal-title":"Infect. Immun."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001409","article-title":"A potential new pathway for Staphylococcus aureus dissemination: the silent survival of S. aureus phagocytosed by human monocyte-derived macrophages.","volume":"3","author":"Kubica","year":"2008","journal-title":"PLoS One"},{"key":"B13","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/nature16057","article-title":"Novel antibody-antibiotic conjugate eliminates intracellular S. aureus.","volume":"527","author":"Lehar","year":"2015","journal-title":"Nature"},{"key":"B14","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1093\/infdis\/jiv388","article-title":"Nonstable Staphylococcus aureus small-colony variants are induced by low pH and sensitized to antimicrobial therapy by phagolysosomal alkalinization.","volume":"213","author":"Leimer","year":"2016","journal-title":"J. Infect. Dis."},{"key":"B15","doi-asserted-by":"crossref","first-page":"520","DOI":"10.1056\/NEJM199808203390806","article-title":"Staphylococcus aureus infections.","volume":"339","author":"Lowy","year":"1998","journal-title":"N. Engl. J. Med."},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0207312","article-title":"Intraphagolysosomal conditions predispose to Staphylococcus epidermidis small colony variants persistence in macrophages.","volume":"13","author":"Magry\u015b","year":"2018","journal-title":"PLoS One"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1128\/aac.01146-08","article-title":"Intracellular activity of antibiotics in a model of human THP-1 macrophages infected by a Staphylococcus aureus small-colony variant strain isolated from a cystic fibrosis patient: study of antibiotic combinations.","volume":"53","author":"Nguyen","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1830","DOI":"10.1128\/iai.03016-14","article-title":"Staphylococcus aureus adapts to oxidative stress by producing H2O2-resistant small-colony variants via the SOS response.","volume":"83","author":"Painter","year":"2015","journal-title":"Infect. Immun."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2014.00099","article-title":"Staphylococcus aureus small colony variants (SCVs): a road map for the metabolic pathways involved in persistent infections.","volume":"4","author":"Proctor","year":"2014","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B20","doi-asserted-by":"publisher","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":"B21","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1038\/nrmicro1384","article-title":"Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections.","volume":"4","author":"Proctor","year":"2006","journal-title":"Nat. Rev. Microbiol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1172\/jci109844","article-title":"Early bacterial clearance from murine lungs. Species-dependent phagocyte response.","volume":"66","author":"Rehm","year":"1980","journal-title":"J. Clin. Invest."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2017.01354","article-title":"Intracellular survival of Staphylococcus aureus in endothelial cells: a matter of growth or persistence.","volume":"19","author":"Rollin","year":"2017","journal-title":"Front. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1443","DOI":"10.1128\/aac.00205-10","article-title":"Intra- and extracellular activities of dicloxacillin and linezolid against a clinical Staphylococcus aureus strain with a small-colony-variant phenotype in an in vitro model of THP-1 macrophages and an in vivo mouse peritonitis model.","volume":"55","author":"Sandberg","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"B25","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1078\/1438-4221-00282","article-title":"Mutations are involved in emergence of aminoglycoside-induced small colony variants of Staphylococcus aureus.","volume":"293","author":"Schaaff","year":"2003","journal-title":"Int. J. Med. Microbiol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1016\/j.cmi.2016.06.020","article-title":"Post-invasion events after infection with Staphylococcus aureus are strongly dependent on both the host cell type and the infecting S. aureus strain.","volume":"22","author":"Strobel","year":"2016","journal-title":"Clin. Microbiol. Infect."},{"key":"B27","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1038\/nrmicro2508","article-title":"Are bloodstream leukocytes Trojan Horses for the metastasis of Staphylococcus aureus?","volume":"9","author":"Thwaites","year":"2011","journal-title":"Nat. Rev. Microbiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1086\/656047","article-title":"Staphylococcus aureus small-colony variants are adapted phenotypes for intracellular persistence.","volume":"202","author":"Tuchscherr","year":"2010","journal-title":"J. Infect. Dis."},{"key":"B29","doi-asserted-by":"publisher","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":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.01866","article-title":"Novel pathways for ameliorating the fitness cost of gentamicin resistant small colony variants.","volume":"7","author":"Vestergaard","year":"2016","journal-title":"Front. Microbiol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.ijantimicag.2007.10.026","article-title":"Staphylococcus aureus small colony variants: a challenge to microbiologists and clinicians.","volume":"31","author":"von Eiff","year":"2008","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B32","doi-asserted-by":"publisher","first-page":"4706","DOI":"10.1128\/jb.179.15.4706-4712.1997","article-title":"A site-directed Staphylococcus aureus hemB mutant is a small-colony variant which persists intracellularly.","volume":"179","author":"von Eiff","year":"1997","journal-title":"J. Bacteriol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"687","DOI":"10.1128\/jb.188.2.687-693.2006","article-title":"henotype microarray profiling of Staphylococcus aureus menD and hemB mutants with the small-colony-variant phenotype.","volume":"188","author":"von Eiff","year":"2006","journal-title":"J. Bacteriol."},{"key":"B34","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-06527-0","article-title":"Prolonged bacterial lag time results in small colony variants that represent a sub-population of persisters.","volume":"9","author":"Vulin","year":"2018","journal-title":"Nat. Commun."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fmicb.2020.01300\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T08:09:22Z","timestamp":1591949362000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fmicb.2020.01300\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,12]]},"references-count":34,"alternative-id":["10.3389\/fmicb.2020.01300"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2020.01300","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,12]]},"article-number":"1300"}}