BACKGROUND: To investigate the role of outer membrane proteins in Acinetobacter baumannii resistant to imipenem, 2 strains were procured from the same patient. METHODS: The imipenem-resistant strain was obtained following a period of imipenem treatment in vivo. The multilocus sequence typing and repetitive extragenic palindromic PCR results indicated that the imipenem-resistant strain originated from the sensitive one. RESULTS: Isoelectric focusing detected no carbapenemases, with neither OXA carbapenemases nor metallo-β-lactamases found. Mass spectrophotometric analysis revealed that 3 outer membrane proteins were expressed differentially in the 2 strains: 2 downregulated proteins (OprD and CarO) and 1 upregulated the 34-kDa efflux pump protein in the resistant strain. A 32-fold decrease in the MIC for imipenem in the presence of Phe-Arg-β-naphthylamide in the same strain indicated a possible involvement of the efflux pump mechanism in its resistance, which was consistent with the findings that the mRNA expression of the 34-kDa efflux pump gene was almost fivefold upregulated in the imipenem-resistant strain compared with that in the imipenem-sensitive strain. Such a significant difference, however, was not found in the expression of AdeB and AdeJ between the 2 strains, and AdeE was not detected. CONCLUSIONS: Our results suggested that downregulation of outer membrane proteins in conjunction with efflux pump overexpression might contribute to imipenem resistance induced in vivo in A. baumannii.
BACKGROUND: To investigate the role of outer membrane proteins in Acinetobacter baumannii resistant to imipenem, 2 strains were procured from the same patient. METHODS: The imipenem-resistant strain was obtained following a period of imipenem treatment in vivo. The multilocus sequence typing and repetitive extragenic palindromic PCR results indicated that the imipenem-resistant strain originated from the sensitive one. RESULTS: Isoelectric focusing detected no carbapenemases, with neither OXA carbapenemases nor metallo-β-lactamases found. Mass spectrophotometric analysis revealed that 3 outer membrane proteins were expressed differentially in the 2 strains: 2 downregulated proteins (OprD and CarO) and 1 upregulated the 34-kDa efflux pump protein in the resistant strain. A 32-fold decrease in the MIC for imipenem in the presence of Phe-Arg-β-naphthylamide in the same strain indicated a possible involvement of the efflux pump mechanism in its resistance, which was consistent with the findings that the mRNA expression of the 34-kDa efflux pump gene was almost fivefold upregulated in the imipenem-resistant strain compared with that in the imipenem-sensitive strain. Such a significant difference, however, was not found in the expression of AdeB and AdeJ between the 2 strains, and AdeE was not detected. CONCLUSIONS: Our results suggested that downregulation of outer membrane proteins in conjunction with efflux pump overexpression might contribute to imipenem resistance induced in vivo in A. baumannii.
Authors: Craig J McPherson; Lisa M Aschenbrenner; Brian M Lacey; Kelly C Fahnoe; Margaret M Lemmon; Steven M Finegan; Baswanth Tadakamalla; John P O'Donnell; John P Mueller; Andrew P Tomaras Journal: Antimicrob Agents Chemother Date: 2012-10-01 Impact factor: 5.191
Authors: Krisztina M Papp-Wallace; Baui Senkfor; Julian Gatta; Weirui Chai; Magdalena A Taracila; Veerabahu Shanmugasundaram; Seungil Han; Richard P Zaniewski; Brian M Lacey; Andrew P Tomaras; Marion J Skalweit; Michael E Harris; Louis B Rice; John D Buynak; Robert A Bonomo Journal: Antimicrob Agents Chemother Date: 2012-08-20 Impact factor: 5.191
Authors: Andrew P Tomaras; Jared L Crandon; Craig J McPherson; Mary Anne Banevicius; Steven M Finegan; Rebecca L Irvine; Matthew F Brown; John P O'Donnell; David P Nicolau Journal: Antimicrob Agents Chemother Date: 2013-06-17 Impact factor: 5.191