title: Clonality, outer-membrane proteins profile and efflux pump in KPC- producing Enterobacter sp. in Brazil.
abstract: Carbapenems resistance in Enterobacter spp. has increased in the last decade, few studies, however, described the mechanisms of resistance in this bacterium. This study evaluated clonality and mechanisms of carbapenems resistance in clinical isolates of Enterobacter spp. identified in three hospitals in Brazil (Hospital A, B and C) over 7-year.
  
  
  
  Antibiotics sensitivity, pulsed-field gel electrophoresis (PFGE), PCR for carbapenemase and efflux pump genes were performed for all carbapenems-resistant isolates. Outer-membrane protein (OMP) was evaluated based on PFGE profile.
  
  
  
  A total of 130 isolates of Enterobacter spp were analyzed, 44/105 (41, 9%) E. aerogenes and 8/25 (32,0%) E. cloacae were resistant to carbapenems. All isolates were susceptible to fosfomycin, polymyxin B and tigecycline. KPC was present in 88.6% of E. aerogenes and in all E. cloacae resistant to carbapenems. The carbapenems-resistant E. aerogenes identified in hospital A belonged to six clones, however, a predominant clone was identified in this hospital over the study period. There is a predominant clone in Hospital B and Hospital C as well. The mechanisms of resistance to carbapenems differ among subtypes. Most of the isolates co-harbored blaKPC, blaTEM and /or blaCTX associated with decreased or lost of 35-36KDa and or 39 KDa OMP. The efflux pump AcrAB-TolC gene was only identified in carbapenems-resistant E. cloacae.
  
  
  
  There was a predominant clone in each hospital suggesting that cross-transmission of carbapenems-resistant Enterobacter spp. was frequent. The isolates presented multiple mechanisms of resistance to carbapenems including OMP alteration.
authors.affiliation: Department of Infectious Diseases, University of São Paulo, Laboratory of Medical Investigation 54 (LIM-54), Hospital Das Clínicas FMUSP, São Paulo, Brazil.
authors.forename: Juliana Ferraz
authors.initials: JF
authors.lastname: Rosa
authors.affiliation: Department of Infectious Diseases, University of São Paulo, Laboratory of Medical Investigation 54 (LIM-54), Hospital Das Clínicas FMUSP, São Paulo, Brazil.
authors.forename: Camila
authors.initials: C
authors.lastname: Rizek
authors.affiliation: Department of Infectious Diseases, University of São Paulo, Laboratory of Medical Investigation 54 (LIM-54), Hospital Das Clínicas FMUSP, São Paulo, Brazil.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Marchi
authors.affiliation: Department of Infectious Diseases, University of São Paulo, Laboratory of Medical Investigation 54 (LIM-54), Hospital Das Clínicas FMUSP, São Paulo, Brazil.
authors.forename: Thais
authors.initials: T
authors.lastname: Guimaraes
authors.affiliation: Hospital de Itapecerica da Serra, Itapecerica da Serra, SP, Brazil.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Miranda
authors.affiliation: Hospital University of Londrina, Londrina, Paraná, Brazil.
authors.forename: Claudia
authors.initials: C
authors.lastname: Carrilho
authors.affiliation: Department of Infectious Diseases, University of São Paulo, Laboratory of Medical Investigation 54 (LIM-54), Hospital Das Clínicas FMUSP, São Paulo, Brazil.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Levin
authors.affiliation: LIM-54, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. costasilviaf@ig.com.br.
authors.forename: Silvia F
authors.initials: SF
authors.lastname: Costa
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D001938:Brazil; D015780:Carbapenems / Q000494:pharmacology; D004269:DNA, Bacterial / Q000235:genetics; D024881:Drug Resistance, Bacterial; D016521:Electrophoresis, Gel, Pulsed-Field / Q000379:methods; D004754:Enterobacter / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification / Q000472:pathogenicity; D004756:Enterobacteriaceae Infections / Q000382:microbiology; D005260:Female; D005578:Fosfomycin / Q000494:pharmacology; D005798:Genes, Bacterial; D006761:Hospitals; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008911:Minocycline / Q000031:analogs & derivatives / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011112:Polymyxin B / Q000494:pharmacology; D000078304:Tigecycline; D055815:Young Adult; D018440:beta-Lactam Resistance / Q000235:genetics*; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015780:Carbapenems; D004269:DNA, Bacterial; D008565:Membrane Proteins; D005578:Fosfomycin; D000078304:Tigecycline; D001618:beta-Lactamases; C063912:carbapenemase; D008911:Minocycline; D011112:Polymyxin B
keywords: Carbapenems; E. aerogenes; E. cloacae; Efflux Pump; Outer Membrane Proteins; Resistance; β-lactamases and Activity efflux pump with inhibitor Carbonyl-cyanide-m-chlorophenylhydrazone (CCCP)