title: Microbicides Alter the Expression and Function of RND-Type Efflux Pump AdeABC in Biofilm-Associated Cells of Acinetobacter baumannii Clinical Isolates.
abstract: Acinetobacter baumannii is a Gram-negative bacterium that causes nosocomial infections worldwide. This microbe's propensity to form biofilms allows it to persist and to survive on clinical abiotic surfaces for long periods. In fact, A. baumannii biofilm formation and its multidrug-resistant nature severely compromise our capacity to care for patients in hospital environments. In contrast, microbicides such as cetrimide (CT) and chlorhexidine (CHX) play important roles in the prevention and treatment of infections. We assessed the efficacy of CT and CHX, either alone or in combination, in eradicating A. baumannii biofilms formed by clinical isolates, by using stainless steel washers to mimic hard abiotic surfaces found in hospital settings. We demonstrated that increasing amounts of each microbicide, alone or in combination, were able to damage and to reduce the viability of A. baumannii biofilms efficaciously. Interestingly, the adeB gene of the resistance-nodulation-cell division (RND) family is predominantly associated with acquired resistance to antimicrobials in A. baumannii. We showed that CT and CHX adversely modified the expression and function of the RND-type efflux pump AdeABC in biofilm-associated A. baumannii cells. Furthermore, we established that these microbicides decreased the negative charges on A. baumannii cell membranes, causing dysregulation of the efflux pump and leading to cell death. Our findings suggest that CT and CHX, alone or in combination, can be used efficaciously for eradication of A. baumannii from hospital surfaces, in order to reduce infections caused by this nosocomial agent.
authors.affiliation: Department of Biomedical Sciences, NYIT College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, New York, USA.
authors.forename: Suvarna
authors.initials: S
authors.lastname: Krishnamoorthy
authors.affiliation: Department of Biomedical Sciences, NYIT College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, New York, USA.
authors.forename: Bhavikkumar P
authors.initials: BP
authors.lastname: Shah
authors.affiliation: Department of Biomedical Sciences, NYIT College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, New York, USA.
authors.forename: Hiu Ham
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Sciences, NYIT College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, New York, USA lmarti13@nyit.edu.
authors.forename: Luis R
authors.initials: LR
authors.lastname: Martinez
mesh_terms: D000151:Acinetobacter Infections / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000494:pharmacology*; D002710:Chlorhexidine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D055672:Static Electricity
chemical_list: C445684:AdeB protein, Acinetobacter baumannii; D000891:Anti-Infective Agents, Local; D001426:Bacterial Proteins; D002593:Cetrimonium Compounds; D026901:Membrane Transport Proteins; D002710:Chlorhexidine; D000077286:Cetrimonium