Relationship between β-lactamase production, outer membrane protein and penicillin-binding protein profiles on the activity of carbapenems against clinical isolates of Acinetobacter baumannii

• Published in: Journal of antimicrobial chemotherapy Vol. 51; no. 3; pp. 565 - 574
• Main Authors: Fernández-Cuenca, Felipe, Martínez-Martínez, Luis, Conejo, Mª Carmen, Ayala, Juan A., Perea, Evelio J., Pascual, Alvaro
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2003
• Subjects: Acinetobacter baumannii; Acinetobacter baumannii - drug effects; Acinetobacter baumannii - enzymology; Acinetobacter baumannii - genetics; Acinetobacter baumannii - isolation & purification; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacterial Outer Membrane Proteins - biosynthesis; Bacterial Outer Membrane Proteins - genetics; Bacterial Proteins; Bacteriology; beta-Lactamases - biosynthesis; Biological and medical sciences; carbapenems; Carbapenems - pharmacology; Carrier Proteins - biosynthesis; Carrier Proteins - genetics; Drug Resistance, Multiple, Bacterial - physiology; Fundamental and applied biological sciences. Psychology; Hexosyltransferases; Humans; Medical sciences; Metabolism. Enzymes; Microbiology; Muramoylpentapeptide Carboxypeptidase - biosynthesis; Muramoylpentapeptide Carboxypeptidase - genetics; outer membrane proteins; Penicillin-Binding Proteins; Peptidoglycan - biosynthesis; Peptidyl Transferases; Pharmacology. Drug treatments; β-lactamases; Human; Enzyme; Neisseriaceae; β-Lactamase; In vitro; Biological activity; Penicillin binding protein; Resistance; Acinetobacter baumannii; Antibiotic; Carbapenem derivatives; Sensitivity resistance; Bacteria; Hydrolases; Micrococcales; Antibacterial agent; Mechanism of action; Clinical isolate
• ISSN: 0305-7453; 1460-2091; 1460-2091
• DOI: 10.1093/jac/dkg097

Twenty blood isolates of Acinetobacter baumannii were studied, representing eight pulsed-field gel electrophoresis patterns and all different antimicrobial susceptibility patterns observed during 1995–97 at the University Hospital Virgen Macarena, Seville, Spain. The MIC90s (mg/L) of imipenem and meropenem decreased from 16 to 0.5 and from 8 to 4, respectively, in the presence of BRL 42715 (BRL) but not clavulanic acid. Hydrolysing activity (nmol/min/mg) of bacterial supernatants against cefaloridine ranged from 8.8 to 552.3 for A. baumannii type I (imipenem MICs ≤ 2), which expressed only a β-lactamase of pI ≥ 9, and from 12.3 to 1543.5 for A. baumannii type II (imipenem MICs ≥ 4), which expressed a β-lactamase of pI ≥ 9 and two others of pI 6.3 and 7. The hydrolysing activities of A. baumannii type II against imipenem, meropenem and oxacillin were higher than those observed for A. baumannii type I. Ten outer membrane protein (OMP) profiles (A. baumannii types I and II) were visualized on 10% SDS–PAGE gels with 6 M urea, whereas only five OMP profiles (A. baumannii types I and II) were differentiated in 12% SDS–PAGE gels. Five A. baumannii with OMP profile type B, characterized by the absence of a 22.5 kDa OMP, were resistant to meropenem and/or imipenem. Twelve penicillin-binding protein (PBP) patterns were observed. PBP patterns of A. baumannii type II were characterized by the absence of a 73.2 kDa band (PBP 2). We concluded that production of β-lactamases of pI 6.3 and 7.0 and reduced expression of PBP 2 are the most frequently observed mechanisms of resistance to carbapenems. In some isolates, loss of a 22.5 kDa OMP is also related to resistance to carbapenems.