Identification and evolution of drug efflux pump in clinical Enterobacter aerogenes strains isolated in 1995 and 2003

• Published in: PloS one 2008-09, Vol.3 (9), p.e3203
• Main Authors: Chevalier, Jacqueline, Mulfinger, Céline, Garnotel, Eric, Nicolas, Pierre, Davin-Régli, Anne, Pagès, Jean-Marie
• Format: Article
• Language: English
• Subjects: Aerogenes; Antibacterial agents; Antibiotic resistance; Antibiotics; Antimicrobial agents; Bacteria; Bacterial infections; Bacterial Typing Techniques; beta-Lactamases - metabolism; Chloramphenicol; Chloramphenicol - metabolism; Clinical isolates; Cloning; Cross infection; Deoxyribonucleic acid; DNA; Drug resistance; Drug Resistance, Multiple; Drug Resistance, Multiple, Bacterial - drug effects; Drug Resistance, Multiple, Bacterial - genetics; Drug therapy; Drugs; E coli; Efflux; Enterobacter aerogenes; Enterobacter aerogenes - genetics; Enterobacter aerogenes - metabolism; Enterobacteriaceae; Enterobacteriaceae Infections - epidemiology; Enterobacteriaceae Infections - genetics; Epidemics; Epidemiology; Erosion processes; Erosion resistance; Escherichia coli; Escherichia coli Proteins - metabolism; Evolution; Evolutionary biology; Expulsion; Gram-negative bacteria; Health aspects; Humans; Infections; Infectious diseases; Infectious Diseases/Antimicrobials and Drug Resistance; Infectious Diseases/Bacterial Infections; Inhibitors; Laboratories; Lactams; Lipoproteins - metabolism; Membrane Transport Proteins - metabolism; Microbial drug resistance; Microbial Sensitivity Tests; Microbiology; Microbiology/Medical Microbiology; Models, Biological; Mortality; Multidrug resistance; Mutation; Neisseria gonorrhoeae; Pathogenesis; Porins - genetics; Pumps; Quinolones; Salmonella; Salmonella Typhimurium; Species Specificity; Strains (organisms); Stress response; Surveillance; Time Factors
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0003203

The high mortality impact of infectious diseases will increase due to accelerated evolution of antibiotic resistance in important human pathogens. Development of antibiotic resistance is a evolutionary process inducing the erosion of the effectiveness of our arsenal of antibiotics. Resistance is not necessarily limited to a single class of antibacterial agents but may affect many unrelated compounds; this is termed 'multidrug resistance' (MDR). The major mechanism of MDR is the active expulsion of drugs by bacterial pumps; the treatment of gram negative bacterial infections is compromised due to resistance mechanisms including the expression of efflux pumps that actively expel various usual antibiotics (beta-lactams, quinolones, ...). Enterobacter aerogenes has emerged among Enterobacteriaceae associated hospital infections during the last twenty years due to its faculty of adaptation to antibiotic stresses. Clinical isolates of E. aerogenes belonging to two strain collections isolated in 1995 and 2003 respectively, were screened to assess the involvement of efflux pumps in antibiotic resistance. Drug susceptibility assays were performed on all bacterial isolates and an efflux pump inhibitor (PAbetaN) previously characterized allowed to decipher the role of efflux in the resistance. Accumulation of labelled chloramphenicol was monitored in the presence of an energy poison to determine the involvement of active efflux on the antibiotic intracellular concentrations. The presence of the PAbetaN-susceptible efflux system was also identified in resistant E. aerogenes strains. For the first time a noticeable increase in clinical isolates containing an efflux mechanism susceptible to pump inhibitor is report within an 8 year period. After the emergence of extended spectrum beta-lactamases in E. aerogenes and the recent characterisation of porin mutations in clinical isolates, this study describing an increase in inhibitor-susceptible efflux throws light on a new step in the evolution of mechanism in E. aerogenes.