title: Efflux pumps expression and its association with porin down-regulation and beta-lactamase production among Pseudomonas aeruginosa causing bloodstream infections in Brazil.
abstract: BACKGROUND
  Multi-drug efflux pumps have been increasingly recognized as a major component of resistance in P. aeruginosa. We have investigated the expression level of efflux systems among clinical isolates of P. aeruginosa, regardless of their antimicrobial susceptibility profile.
  
  
  RESULTS
  Aztreonam exhibited the highest in vitro activity against the P. aeruginosa isolates studied (64.4% susceptibility), whereas susceptibility rates of imipenem and meropenem were both 47.5%. The MexXY-OprM and MexAB-OprM efflux systems were overexpressed in 50.8% and 27.1% of isolates studied, respectively. Overexpression of the MexEF-OprN and MexCD-OprJ systems was not observed. AmpC beta-lactamase was overexpressed in 11.9% of P. aeruginosa isolates. In addition, decreased oprD expression was also observed in 69.5% of the whole collection, and in 87.1% of the imipenem non-susceptible P. aeruginosa clinical isolates. The MBL-encoding genes blaSPM-1 and blaIMP-1 were detected in 23.7% and 1.7% P. aeruginosa isolates, respectively. The blaGES-1 was detected in 5.1% of the isolates, while blaGES-5 and blaCTX-M-2 were observed in 1.7% of the isolates evaluated. In the present study, we have observed that efflux systems represent an adjuvant mechanism for antimicrobial resistance.
  
  
  CONCLUSIONS
  Efflux systems in association of distinct mechanisms such as the porin down-regulation, AmpC overproduction and secondary beta-lactamases play also an important role in the multi-drug resistance phenotype among P. aeruginosa clinical isolates.
authors: Division of Infectious Diseases, Universidade Federal de São Paulo, Rua Pedro de Toledo 781, 04039-032 São Paulo, Brazil. danilo.elias@gmail.com
authors: Danilo E
authors: DE
authors: Xavier
authors: Renata C
authors: RC
authors: Picão
authors: Raquel
authors: R
authors: Girardello
authors: Lorena C C
authors: LC
authors: Fehlberg
authors: Ana C
authors: AC
authors: Gales
mesh_terms: D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia / Q000378:metabolism* / Q000382:microbiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001938:Brazil; D002648:Child; D015536:Down-Regulation; D018432:Drug Resistance, Multiple; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D018272:Porins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011552:Pseudomonas Infections / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D018272:Porins; D001618:beta-Lactamases