{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T06:07:58Z","timestamp":1791094078277,"version":"4.1.0"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2008,8,1]],"date-time":"2008-08-01T00:00:00Z","timestamp":1217548800000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2008,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p><jats:italic>Staphylococcus aureus<\/jats:italic>invades eukaryotic cells. When methicillin-resistant<jats:italic>S. aureus<\/jats:italic>(MRSA) ATCC 33591 is phagocytized by human THP-1 macrophages, complete restoration of susceptibility to cloxacillin and meropenem is shown and the strain becomes indistinguishable from MSSA ATCC 25923 due to the acid pH prevailing in phagolysosomes (S. Lemaire et al., Antimicrob. Agents Chemother. 51:1627-1632, 2007). We examined whether this observation can be extended to (i) strains of current clinical and epidemiological interest (three hospital-acquired MRSA [HA-MRSA] strains, two community-acquired MRSA [CA-MRSA] strains, two HA-MRSA strains with the vancomycin-intermediate phenotype, one HA-MRSA strain with the vancomycin-resistant phenotype, and one animal [porcine] MRSA strain), (ii) activated THP-1 cells and nonprofessional phagocytes (keratinocytes, Calu-3 bronchial epithelial cells), and (iii) other \u03b2-lactams (imipenem, oxacillin, cefuroxime, cefepime). All strains showed (i) a marked reduction in MICs in broth at pH 5.5 compared with the MIC at pH 7.4 and (ii) sigmoidal dose-response curves with cloxacillin (0.01\u00d7 to 100\u00d7 MIC, 24 h of incubation) after phagocytosis by THP-1 macrophages that were indistinguishable from each other and from the dose-response curve for methicillin-susceptible<jats:italic>S. aureus<\/jats:italic>(MSSA) ATCC 25923 (relative potency [50% effect], 6.09\u00d7 MIC [95% confidence interval {CI}, 4.50 to 8.25]; relative efficacy [change in bacterial counts over the original inoculum for an infinitely large cloxacillin concentration, or maximal effect], \u22120.69 log CFU [95% CI, \u22120.79 to \u22120.58]). Similar dose-response curves for cloxacillin were also observed with MSSA ATCC 25923 and MRSA ATCC 33591 after phagocytosis by activated THP-1 macrophages, keratinocytes, and Calu-3 cells. By contrast, there was a lower level of restoration of susceptibility of MRSA ATCC 33591 to cefuroxime and cefepime after phagocytosis by THP-1 macrophages, even when the data were normalized for differences in MICs. We conclude that the restoration of MRSA susceptibility to \u03b2-lactams after phagocytosis is independent of the strain and the types of cells but varies between \u03b2-lactams.<\/jats:p>","DOI":"10.1128\/aac.00123-08","type":"journal-article","created":{"date-parts":[[2008,6,3]],"date-time":"2008-06-03T00:58:18Z","timestamp":1212454698000},"page":"2797-2805","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Restoration of Susceptibility of Intracellular Methicillin-Resistant<i>Staphylococcus aureus<\/i>to \u03b2-Lactams: Comparison of Strains, Cells, and Antibiotics"],"prefix":"10.1128","volume":"52","author":[{"given":"Sandrine","family":"Lemaire","sequence":"first","affiliation":[{"name":"Unite\u0301 de Pharmacologie Cellulaire et Mole\u0301culaire, Universite\u0301 Catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aure\u0301lie","family":"Olivier","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Pharmacologie Cellulaire et Mole\u0301culaire, Universite\u0301 Catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franc\u0327oise","family":"Van Bambeke","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Pharmacologie Cellulaire et Mole\u0301culaire, Universite\u0301 Catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul M.","family":"Tulkens","sequence":"additional","affiliation":[{"name":"Unite\u0301 de Pharmacologie Cellulaire et Mole\u0301culaire, Universite\u0301 Catholique de Louvain, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter C.","family":"Appelbaum","sequence":"additional","affiliation":[{"name":"Department of Pathology, Penn State Milton S. 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