Synergistic effects of anti-CmeA and anti-CmeB peptide nucleic acids on sensitizing Campylobacter jejuni to antibiotics. Antimicrob Agents Chemother;57:4575

Abstract

The CmeABC efflux pump in Campylobacter jejuni confers resistance to structurally divergent antimicrobials, and inhibition of CmeABC represents a promising strategy to control antibiotic-resistant Campylobacter. Antisense peptide nucleic acids (PNAs) targeting the three components of CmeABCwere evaluated for inhibition of CmeABC expression. The result revealed a synergis-tic effect of the PNAs targeting CmeA and CmeB on sensitizing C. jejuni to antibiotics. This finding further demonstrates the feasibility of using PNAs to potentiate antibiotics against antibiotic-resistant Campylobacter. Campylobacter jejuni is a major food-borne pathogen account-ing for 400 to 500 million cases of diarrhea each year world-wide (1). This organism is increasingly resistant to clinically important antibiotics, particularly fluoroquinolone (FQ) antimi-crobials (2). The CmeABC efflux pump in Campylobacter confers resistance to a broad range of antimicrobials and toxic com-pounds (3). In addition, this efflux pump functions synergistically with othermechanisms (e.g., spontaneousmutations in antibiotic targets) inmediating high-level resistance to antibiotics (3). Cme-ABC is also important for bile resistance and is essential for Cam-pylobacter colonization in the intestinal tract of animal hosts (4)