{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:55:52Z","timestamp":1791233752322,"version":"4.1.0"},"reference-count":30,"publisher":"Bentham Science Publishers Ltd.","issue":"1","license":[{"start":{"date-parts":[[2017,6,30]],"date-time":"2017-06-30T00:00:00Z","timestamp":1498780800000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/legalcode"}],"content-domain":{"domain":["openmicrobiologyjournal.com","benthamopen.com"],"crossmark-restriction":true},"short-container-title":["TOMICROJ"],"published-print":{"date-parts":[[2017,6,30]]},"abstract":"<jats:sec><jats:title>Objectives:<\/jats:title><jats:p>Methicillin-resistant<jats:italic>Staphylococcus aureus<\/jats:italic>(MRSA) across the world often leave clinicians with little or no choice of treatment options. The multi-drug efflux (MDE) genes are bacterial survival mechanisms responsible for the pumping out of antibiotics and other biocides from the cytoplasm. Whilst effort is being made in the development of antibiotic adjuvants such as efflux pumps inhibitors, information is needed on the diversity of these MDEs in the circulating<jats:italic>S. aureus<\/jats:italic>and on the growth dynamics of the clinical isolates in response to antibiotics is not regularly examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods:<\/jats:title><jats:p>Here, we evaluated the diversity of MDEs in cinical<jats:italic>S. aureus<\/jats:italic>recovered in a tertiary academic hospital, Pretoria, South African hospital using PCR and also employed visual minimum inhibitory concentration and quantitative analysis of spectrophometric measurements of bacterial growth in the presence of a model \u03b2 lactam antibiotic (methicillin), to phenotypically elucidate the resistance pattern of these isolates in response to methicillin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results:<\/jats:title><jats:p>Three major distribution patterns of MDEs were observed in the clinical isolates evaluated. Moreover,<jats:italic>nor<\/jats:italic>A,<jats:italic>nor<\/jats:italic>B and<jats:italic>tet<\/jats:italic>38 were present in 98.9% of the isolates while other MDE were present in different proportions ranging from 40 to 98.6% of the isolates. In addition,<jats:italic>S. aureus<\/jats:italic>isolates, be it of MRSA or MSSA genotype did not habour the same set of MDEs despite being recovered from the same hospital setting. Finally, we showed that MSSA displayed phenotypic resistance to methicilllin despite the non-detection of the<jats:italic>mec<\/jats:italic>A resistance gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions:<\/jats:title><jats:p>Our data suggest that the growth of<jats:italic>S. aureus<\/jats:italic>may be enhanced by \u03b2 lactams (methicillin) and that MSSA may also display resistance to methicillin and perhaps other \u03b2 lactam antibiotics. The high prevalence of MDEs suggestive of resistance to a broad spectrum of biocides and fluoroquinolones are particularly disturbing.<\/jats:p><\/jats:sec>","DOI":"10.2174\/1874285801711010132","type":"journal-article","created":{"date-parts":[[2017,7,17]],"date-time":"2017-07-17T09:13:45Z","timestamp":1500282825000},"page":"132-141","update-policy":"https:\/\/doi.org\/10.2174\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Diversity of Multidrug Efflux Genes and Phenotypic Evaluation of the In vitro Resistance Dynamics of Clinical Staphylococcus Aureus Isolates Using Methicillin; a Model \u03b2-lactam"],"prefix":"10.2174","volume":"11","author":[{"given":"John F.","family":"Antiabong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen M.","family":"Kock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nontombi M.","family":"Mbelle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marthie M.","family":"Ehlers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"965","reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0934-8840(98)80165-5","volume":"287","author":"Mlynarczyk A.","year":"1998","unstructured":"Mlynarczyk A, Mlynarczyk G, Jeljaszewicz J. The genome of Staphylococcus aureus: A review. Zentralbl Bakteriol 1998; 287 : 277-314.","journal-title":"Zentralbl. Bakteriol."},{"key":"ref2","doi-asserted-by":"crossref","first-page":"59","DOI":"10.2174\/1874285801307010059","volume":"7","author":"Costa S.S.","year":"2013","unstructured":"Costa SS, Viveiros M, Amaral L, Couto I. Multidrug efflux pumps in Staphylococcus aureus: an update. Open Microbiol J 2013; 7 : 59-71.","journal-title":"Open Microbiol. J."},{"key":"ref3","doi-asserted-by":"crossref","first-page":"3144","DOI":"10.1099\/mic.0.2008\/021188-0","volume":"154","author":"Huet A.A.","year":"2008","unstructured":"Huet AA, Raygada JL, Mendiratta K, Seo SM, Kaatz GW. Multidrug efflux pump overexpression in Staphylococcus aureus after single and multiple in vitro exposures to biocides and dyes. Microbiol-Sgm 2008; 154 : 3144-53.","journal-title":"Microbiol-Sgm"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1111\/j.1574-695X.2009.00585.x","volume":"57","author":"Makgotlho P.E.","year":"2009","unstructured":"Makgotlho PE, Kock MM, Hoosen A, et al. Molecular identification and genotyping of MRSA isolates. FEMS Immunol Med Microbiol 2009; 57 : 104-15.","journal-title":"FEMS Immunol. Med. Microbiol."},{"key":"ref5","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1002\/nmi2.53","volume":"2","author":"Oosthuysen W.F.","year":"2014","unstructured":"Oosthuysen WF, Orth H, Lombard C, Sinha B, Wasserman E. In vitro characterization of representative clinical South African Staphylococcus aureus isolates from various clonal lineages. New Microbes New Infect 2014; 2 : 115-22.","journal-title":"New Microbes New Infect."},{"key":"ref6","first-page":"4","author":"Zeng X.","year":"2013","unstructured":"Zeng X, Lin J. Beta-lactamase induction and cell wall metabolism in gram-negative bacteria. Front Microbiol 2013; 4.","journal-title":"Front. Microbiol."},{"key":"ref7","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.gene.2015.03.017","volume":"563","author":"Antiabong J.F.","year":"2015","unstructured":"Antiabong JF, Ball AS, Brown MH. The effects of iron limitation and cell density on prokaryotic metabolism and gene expression: Excerpts from Fusobacterium necrophorum strain 774 (sheep isolate). Gene 2015; 563 : 94-102.","journal-title":"Gene"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1016\/j.mcp.2010.01.001","volume":"24","author":"McClure J.A.","year":"2010","unstructured":"McClure JA, Conly JM, Elsayed S, Zhang K. Multiplex-PCR assay to facilitate identification of the recently described staphylococcal cassette chromosome mec type VIII. Mol Cell Probes 2010; 24 : 229-32.","journal-title":"Mol. Cell. Probes"},{"key":"ref9","unstructured":"Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing. Clinical and Laboratory Standards Institute Twenty-Fouth Informational Supplement Document M100-S24 C, 2014. Wayne, USA. 2014."},{"key":"ref10","doi-asserted-by":"crossref","first-page":"S350","DOI":"10.1086\/533591","volume":"46","author":"Gordon R.J.","year":"2008","unstructured":"Gordon RJ, Lowy FD. Pathogenesis of methicillin-resistant Staphylococcus aureus infection. Clin Infect Dis 2008; 46 : S350-9.","journal-title":"Clin. Infect. Dis."},{"key":"ref11","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1600-0625.2012.01502.x","volume":"21","author":"Van der Kooi-Pol Y.","year":"2012","unstructured":"Van der Kooi-Pol Y. High genetic diversity of staphylococcus aureus strains colonizing patients with epidermolysis bullosa. Exp Dermatol 2012; 21 : 463-6.","journal-title":"Exp. Dermatol."},{"key":"ref12","first-page":"775","volume":"10","author":"Antiabong J.F.","year":"2016","unstructured":"Antiabong JF, Kock MM, Maphanga TG, Salawu AM, Ehlers MM. Diversity of MRSA SCCmec elements in Pretoria region of South Africa: The problem of variation in the assigned SCCmec types by different multiplex-polymerase chain reaction (pcr) methods and a call for an African consensus. Am J Ment Retard 2016; 10 : 775-82.","journal-title":"Am. J. Ment. Retard."},{"key":"ref13","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/phar.1220","volume":"33","author":"Kullar R.","year":"2013","unstructured":"Kullar R, Davis SL, Kaye KS, Levine DP, Pogue JM, Rybak MJ. Implementation of an antimicrobial stewardship pathway with daptomycin for optimal treatment of methicillin-resistant Staphylococcus aureus bacteremia. Pharmacotherapy 2013; 33 : 3-10.","journal-title":"Pharmacotherapy"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"28","DOI":"10.3390\/antibiotics2010028","volume":"2","author":"Handzlik J.","year":"2013","unstructured":"Handzlik J, Matys A, Kie\u0107-Kononowicz K. Recent Advances in Multi-Drug Resistance (MDR) Efflux Pump Inhibitors of Gram-Positive Bacteria S. aureus. Antibiotics (Basel) 2013; 2 : 28.","journal-title":"Antibiotics (Basel)"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1111\/j.1574-6976.2008.00157.x","volume":"33","author":"Martinez J.L.","year":"2009","unstructured":"Martinez JL, Sanchez MB, Martinez-Solano L, et al. Functional role of bacterial multidrug efflux pumps in microbial natural ecosystems. FEMS Microbiol Rev 2009; 33 : 430-49.","journal-title":"FEMS Microbiol. Rev."},{"key":"ref16","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1089\/107662903765826697","volume":"9","author":"Alam M.M.","year":"2003","unstructured":"Alam MM, Kobayashi N, Uehara N, Watanabe N. Analysis on distribution and genomic diversity of high-level antiseptic resistance genes qacA and qacB in human clinical isolates of Staphylococcus aureus. Microb Drug Resist 2003; 9 : 109-21.","journal-title":"Microb. Drug Resist."},{"key":"ref17","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/nrmicro3380","volume":"13","author":"Blair J.M.","year":"2015","unstructured":"Blair JM, Webber MA, Baylay AJ, Ogbolu DO, Piddock LJ. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol 2015; 13 : 42-51.","journal-title":"Nat. Rev. Microbiol."},{"key":"ref18","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1016\/j.femsre.2004.09.003","volume":"29","author":"Begley M.","year":"2005","unstructured":"Begley M, Gahan CG, Hill C. The interaction between bacteria and bile. FEMS Microbiol Rev 2005; 29 : 625-51.","journal-title":"FEMS Microbiol. Rev."},{"key":"ref19","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1194\/jlr.R700016-JLR200","volume":"49","author":"Drake D.R.","year":"2008","unstructured":"Drake DR, Brogden KA, Dawson DV, Wertz PW. Thematic review series: skin lipids. antimicrobial lipids at the skin surface. J Lipid Res 2008; 49 : 4-11.","journal-title":"J. Lipid Res."},{"key":"ref20","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1073\/pnas.91.1.197","volume":"91","author":"Pearson J.P.","year":"1994","unstructured":"Pearson JP, Gray KM, Passador L, et al. Structure of the autoinducer required for expression of Pseudomonas aeruginosa virulence genes. Proc Natl Acad Sci USA 1994; 91 : 197-201.","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"550","DOI":"10.2203\/dose-response.13-002.Migliore","volume":"11","author":"Migliore L.","year":"2013","unstructured":"Migliore L, Rotini A, Thaller MC. Low doses of tetracycline trigger the E. coli growth: A case of hormetic response. Dose Response 2013; 11 : 550-7.","journal-title":"Dose Response"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1016\/j.mib.2006.08.006","volume":"9","author":"Davies J.","year":"2006","unstructured":"Davies J, Spiegelman GB, Yim G. The world of subinhibitory antibiotic concentrations. Curr Opin Microbiol 2006; 9 : 445-53.","journal-title":"Curr. Opin. Microbiol."},{"key":"ref23","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1126\/science.1155157","volume":"320","author":"Dantas G.","year":"2008","unstructured":"Dantas G, Sommer M, Oluwasegun R, Church G. Bacteria subsisting on antibiotics. Science 2008; 320 : 100-3.","journal-title":"Science"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1093\/jac\/47.6.896","volume":"47","author":"Mayer S.","year":"2001","unstructured":"Mayer S, Boos M, Beyer A, Fluit AC, Schmitz FJ. Distribution of the antiseptic resistance genes qacA, qacB and qacC in 497 methicillin-resistant and -susceptible European isolates of Staphylococcus aureus -. J Antimicrob Chemother 2001; 47 : 896-7.","journal-title":"J. Antimicrob. Chemother."},{"key":"ref25","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1128\/JCM.02690-05","volume":"44","author":"Noguchi N.","year":"2006","unstructured":"Noguchi N, Nakaminami H, Nishijima S, Kurokawa I, So H, Sasatsu M. Antimicrobial agent of susceptibilities and antiseptic resistance gene distribution among methicillin-resistant Staphylococcus aureus isolates from patients with impetigo and staphylococcal scalded skin syndrome. J Clin Microbiol 2006; 44 : 2119-25.","journal-title":"J. Clin. Microbiol."},{"key":"ref26","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/1471-2180-11-241","volume":"13","author":"Costa S.S.","year":"2011","unstructured":"Costa SS, Falcao C, Viveiros M, et al. Exploring the contribution of efflux on the resistance to fluoroquinolones in clinical isolates of Staphylococcus aureus. BMC Microbiol 2011; 13 : 241.","journal-title":"BMC Microbiol."},{"key":"ref27","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1093\/jac\/dkn217","volume":"62","author":"Couto I.","year":"2008","unstructured":"Couto I, Costa SS, Viveiros M, Martins M, Amaral L. Efflux-mediated response of Staphylococcus aureus exposed to ethidium bromide. J Antimicrob Chemother 2008; 62 : 504-13.","journal-title":"J. Antimicrob. Chemother."},{"key":"ref28","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1128\/AAC.48.3.909-917.2004","volume":"48","author":"Huang J.","year":"2004","unstructured":"Huang J, O'Toole PW, Shen W, et al. Novel chromosomally encoded multidrug efflux transporter MdeA in Staphylococcus aureus. Antimicrob Agents Chemother 2004; 48 : 909-17.","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref29","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1128\/AEM.59.3.695-700.1993","volume":"59","author":"Muyzer G.","year":"1993","unstructured":"Muyzer G, de Waal EC, Uitterlinden AG. Profiling of complex microbial populations by denaturing gradient gel electrophoresis analysis of polymerase chain reaction-amplified genes coding for 16S rRNA. Appl Environ Microbiol 1993; 59 : 695-700.","journal-title":"Appl. Environ. Microbiol."},{"key":"ref30","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1093\/jac\/47.4.391","volume":"47","author":"Dom\u00ednguez M.C.","year":"2001","unstructured":"Dom\u00ednguez MC, de la Rosa MM, Borobio VM. Application of a spectrophotometric method for the determination of post-antibiotic effect and comparison with viable counts in agar. Antimicrob Chemother 2001; 47 (4) : 391-8.","journal-title":"Antimicrob. Chemother."}],"container-title":["The Open Microbiology Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/openmicrobiologyjournal.com\/contents\/volumes\/V11\/TOMICROJ-11-132\/TOMICROJ-11-132.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openmicrobiologyjournal.com\/contents\/volumes\/V11\/TOMICROJ-11-132\/TOMICROJ-11-132.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/openmicrobiologyjournal.com\/contents\/volumes\/V11\/TOMICROJ-11-132\/TOMICROJ-11-132.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,10,12]],"date-time":"2020-10-12T17:41:51Z","timestamp":1602524511000},"score":1,"resource":{"primary":{"URL":"https:\/\/openmicrobiologyjournal.com\/VOLUME\/11\/PAGE\/132\/"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,6,30]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,6,30]]}},"alternative-id":["TOMICROJ-11-132"],"URL":"https:\/\/doi.org\/10.2174\/1874285801711010132","relation":{},"ISSN":["1874-2858"],"issn-type":[{"value":"1874-2858","type":"print"}],"subject":[],"published":{"date-parts":[[2017,6,30]]},"assertion":[{"value":"Peer Reviewed","order":0,"name":"review_status","label":"Review Status","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Single blind","order":1,"name":"review_process","label":"Review Process","group":{"name":"peer_review_details","label":"Peer Review Details"}},{"value":"Checked with iThenticate","order":0,"name":"screening_status","label":"Screening Status","group":{"name":"plagiarism_screening","label":"Plagiarism Screening"}},{"value":"2016-12-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-04-17","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-04-23","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-06-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}