Identification and evolution of drug efflux pump in clinical Enterobacter aerogenes strains isolated in 1995 and 2003.
BACKGROUND
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, ...).


RESULTS
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.


CONCLUSIONS
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.
Chevalier
Jacqueline
J
UMR-MD1, IFR 48, Facultés de Médecine et de Pharmacie, Marseille, France.
Mulfinger
Céline
C
Garnotel
Eric
E
Nicolas
Pierre
P
Davin-Régli
Anne
A
Pagès
Jean-Marie
JM
D015373:Bacterial Typing Techniques; D002701:Chloramphenicol / Q000378:metabolism; D018432:Drug Resistance, Multiple; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics*; D021902:Enterobacter aerogenes / Q000235:genetics* / Q000378:metabolism*; D004756:Enterobacteriaceae Infections / Q000453:epidemiology* / Q000235:genetics; D029968:Escherichia coli Proteins / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008954:Models, Biological; D009154:Mutation; D018272:Porins / Q000235:genetics; D013045:Species Specificity; D013997:Time Factors; D001618:beta-Lactamases / Q000378:metabolism
C083497:AcrA protein, E coli; D029968:Escherichia coli Proteins; D008074:Lipoproteins; D026901:Membrane Transport Proteins; D018272:Porins; D002701:Chloramphenicol; D001618:beta-Lactamases
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