title: Reduced susceptibility to biocides in Acinetobacter baumannii: association with resistance to antimicrobials, epidemiological behaviour, biological cost and effect on the expression of genes encoding porins and efflux pumps.
abstract: OBJECTIVE
  The objective of this study was to analyse whether there is an association between reduced susceptibility to biocides in Acinetobacter baumannii and (i) antimicrobial resistance (co-resistance), (ii) prevalent (epidemic) clones, (iii) changes in the fitness or (iv) expression of genes related to efflux pumps and porins.
  
  
  METHODS
  Susceptibility to biocides and antimicrobials was determined in 49 clonally unrelated isolates of A. baumannii. Biological cost, in terms of mean generation time, was determined by spectrophotometry. Quantitative real-time RT-PCR was used to determine the relative expression of genes encoding several efflux pumps and porins.
  
  
  RESULTS
  Reduced susceptibility to chlorhexidine digluconate, benzalkonium chloride and Irgasan(®) was associated with resistance to aminoglycosides, tetracycline and ciprofloxacin (P < 0.05). The MICs of carbapenems, aminoglycosides, doxycycline and ciprofloxacin for isolate Ab70 (epidemic clone) exposed to these biocides increased by ≥2 dilutions. Reduced susceptibility to Orsan(®) was more frequent among prevalent clones than non-prevalent clones (P < 0.05). Mean generation times for Ab70 before and after exposure to benzalkonium chloride were 57.8 and 78.1 min, respectively (P = 0.02). Relative expression of abeS and adeB was increased in Ab46 and Ab70 after exposure to chlorhexidine digluconate, but was decreased for ompA and carO after exposure to Irgasan(®).
  
  
  CONCLUSIONS
  Reduced susceptibility to biocides is associated with co-resistance to carbapenems, aminoglycosides, tetracycline and ciprofloxacin. Reduced susceptibility to Orsan(®) may be a marker of prevalent clones. Acquisition of reduced susceptibility to benzalkonium chloride has a biological cost. Exposure to biocides affects the relative expression of genes related to some efflux pump genes (increased expression) or porins (reduced expression).
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas, Microbiología Clínica y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Sevilla, Spain Departamento de Microbiología, Universidad de Sevilla, Sevilla, Spain felipefc@us.es.
authors.forename: Felipe
authors.initials: F
authors.lastname: Fernández-Cuenca
authors.affiliation: Servicio de Microbiología, Complexo Hospitalario Universitario de A Coruña (CHUAC), A Coruña, Spain Instituto de Investigación Biomédica de A Coruña (INIBIC), A Coruña, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Tomás
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas, Microbiología Clínica y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Sevilla, Spain Departamento de Microbiología, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Francisco-Javier
authors.initials: FJ
authors.lastname: Caballero-Moyano
authors.affiliation: Servicio de Microbiología, Complexo Hospitalario Universitario de A Coruña (CHUAC), A Coruña, Spain Instituto de Investigación Biomédica de A Coruña (INIBIC), A Coruña, Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Bou
authors.affiliation: Servicio de Microbiología, Hospital Universitario Marqués de Valdecilla, Santander, Spain Instituto de Investigación Marqués de Valdecilla (IDIVAL), Santander, Spain Departamento de Biología Molecular, Facultad de Medicina, Universidad de Cantabria, Santander, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Martínez-Martínez
authors.affiliation: Department of Clinical Microbiology, Biomedical Diagnostic Centre (CDB), Hospital Clínic, School of Medicine, University of Barcelona, Barcelona, Spain ISGlobal, Barcelona Centre for International Health Research (CRESIB), Hospital Clínic, University of Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas, Microbiología Clínica y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Sevilla, Spain Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain.
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Pachón
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas, Microbiología Clínica y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Sevilla, Spain Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain Instituto de Biomedicina de Sevilla (IBIS), Sevilla, Spain.
authors.forename: José-Miguel
authors.initials: JM
authors.lastname: Cisneros
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas, Microbiología Clínica y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Sevilla, Spain Departamento de Medicina, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Rodríguez-Baño
authors.affiliation: Unidad Clínica de Enfermedades Infecciosas, Microbiología Clínica y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Sevilla, Spain Departamento de Microbiología, Universidad de Sevilla, Sevilla, Spain.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Pascual
mesh_terms: D000151:Acinetobacter Infections / Q000453:epidemiology / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000145:classification / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D004202:Disinfectants / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004734:Energy Metabolism; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D026901:Membrane Transport Proteins / Q000096:biosynthesis; D008826:Microbial Sensitivity Tests; D018272:Porins / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D004202:Disinfectants; D026901:Membrane Transport Proteins; D018272:Porins