Over the past few decades, the emergence of antibacterial resistance has become a major public health issue. The ESKAPEE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. and Escherichia coli) have been identified as the leading cause of multi-drug resistant nosocomial infections as a result of intensive use of broad-spectrum antibiotics to treat these infections. Moreover, overexpression of multi-drug efflux transport systems has been described as one of the most critical resistance mechanisms. As various families of efflux pumps co-exist in A. baumannii like Resistance-Nodulation-Division (RND) tripartite systems and Major Facilitator Superfamily (MFS) proteins, the development of efflux pump inhibitors to help restoring antibiotic activity on resistant strains could be key to new effective treatments. 1-(1-NaphtylMethyl)-Piperazine (NMP) and Phenylalanine-Arginine-β-Naphtylamide (PAβN), already described as efflux pump inhibitors, have been tested on 134 ciprofloxacin resistant strains of A. baumannii collected from clinical isolates in Amiens University Hospital (Amiens, France). An efflux driven mechanism of resistance has been phenotypically detected in 35 strains measuring ciprofloxacin MICs with and without NMP or PAβN. Quantification of mRNA will be performed on these isolates to characterize the overexpressed pumps and identify the origin of this resistance in our local clinical environment. Meanwhile, the synthesis of new NMP analogs has been undertaken. These promising compounds will then be evaluated as efflux pump inhibitors on the 35 isolates of our collection displaying an efflux driven resistance to ciprofloxacin.

Efflux pumps in Acinetobacter baumannii: Molecular characterization and study of new 1-(1-naphtylmethyl)-piperazine analogs as potential inhibitors

2019 Fall National Meeting

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