Rumbo, C.Gato, E.López, M.Ruiz de Alegría, C.Fernández-Cuenca, F.Martínez-Martínez, L.Vila, J.Pachón, J.Cisneros, J. M.Rodríguez-Baño, J.Pascual, A.Bou, G.Tomás, M.2015-10-052015-10-052013-11Rumbo C, Gato E, López M, Ruiz de Alegría C, Fernández-Cuenca F, Martínez-Martínez L, et al. Contribution of efflux pumps, porins, and β-lactamases to multidrug resistance in clinical isolates of Acinetobacter baumannii. Antimicrob Agents Chemother. 2013; 57(11):5247-570066-4804http://hdl.handle.net/10668/2003Journal Article; Research Support, Non-U.S. Gov't;We investigated the mechanisms of resistance to carbapenems, aminoglycosides, glycylcyclines, tetracyclines, and quinolones in 90 multiresistant clinical strains of Acinetobacter baumannii isolated from two genetically unrelated A. baumannii clones: clone PFGE-ROC-1 (53 strains producing the OXA-58 β-lactamase enzyme and 18 strains with the OXA-24 β-lactamase) and clone PFGE-HUI-1 (19 strains susceptible to carbapenems). We used real-time reverse transcriptase PCR to correlate antimicrobial resistance (MICs) with expression of genes encoding chromosomal β-lactamases (AmpC and OXA-51), porins (OmpA, CarO, Omp33, Dcap-like, OprB, Omp25, OprC, OprD, and OmpW), and proteins integral to six efflux systems (AdeABC, AdeIJK, AdeFGH, CraA, AbeM, and AmvA). Overexpression of the AdeABC system (level of expression relative to that by A. baumannii ATCC 17978, 30- to 45-fold) was significantly associated with resistance to tigecycline, minocycline, and gentamicin and other biological functions. However, hyperexpression of the AdeIJK efflux pump (level of expression relative to that by A. baumannii ATCC 17978, 8- to 10-fold) was significantly associated only with resistance to tigecycline and minocycline (to which the TetB efflux system also contributed). TetB and TetA(39) efflux pumps were detected in clinical strains and were associated with resistance to tetracyclines and doxycycline. The absence of the AdeABC system and the lack of expression of other mechanisms suggest that tigecycline-resistant strains of the PFGE-HUI-1 clone may be associated with a novel resistance-nodulation-cell efflux pump (decreased MICs in the presence of the inhibitor Phe-Arg β-naphthylamide dihydrochloride) and the TetA(39) system.enAnti-Bacterial AgentsCarbapenemsPorinsQuinolonesTetracyclinesCL 331002beta-LactamasesAminoglycosidesCarbapenémicosPorinasQuinolonasTetraciclinasbeta-LactamasasAminoglicósidosMedical Subject Headings::Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Gram-Negative Bacterial Infections::Moraxellaceae Infections::Acinetobacter InfectionsMedical Subject Headings::Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Aerobic Bacteria::Gram-Negative Aerobic Rods and Cocci::Moraxellaceae::Acinetobacter::Acinetobacter baumanniiMedical Subject Headings::Chemicals and Drugs::Carbohydrates::Glycosides::AminoglycosidesMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Anti-Infective Agents::Anti-Bacterial AgentsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::CarbapenemsMedical Subject Headings::Phenomena and Processes::Microbiological Phenomena::Bacterial Physiological Phenomena::Drug Resistance, Bacterial::Drug Resistance, Multiple, BacterialMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Membrane Transport Proteins::Ion Channels::PorinsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Microbiological Techniques::Microbial Sensitivity TestsMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::PhylogenyMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Lactams::beta-Lactams::CephalosporinsMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Quinolines::QuinolonesMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Hydrocarbons, Cyclic::Hydrocarbons, Aromatic::Polycyclic Hydrocarbons, Aromatic::Naphthacenes::TetracyclinesMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases::beta-LactamasesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Carrier Proteins::Membrane Transport Proteins::ATP-Binding Cassette Transportersresearch article23939894open access10.1128/AAC.00730-131098-6596PMC3811325