The human male reproductive tract antimicrobial peptides of the HE2 family exhibit potent synergy with standard antibiotics

Abstract

Reproductive tract infections pose a serious threat to healthandfertility. Duetotheemergenceofantibiotic resistant pathogens, antimicrobial proteins and peptides of the reproductive tract are extensively characterized in recent years toward developing newer strategies to treat genital tract infections. Pathogen growth inhibition using a combination of naturally occurring male reproductive tract antimicrobial peptides and commonly used antibiotics has not been reported. Checker board analyses were carried out to determine the nature of interaction (synergistic, additive and antagonistic) between HE2α and HE2β2 peptides and the commonly used antibiotics. Using Escherichia coli as the target organism, theminimal inhibitory concentration and fractional inhibitory concentration indices were determined. We demonstrate for the first time that the human male reproductive tract antimicrobial peptides HE2α and HE2β2 act synergistically with the commonly used antibiotics to inhibit E. coli growth. A combination of HE2α and HE2β2 peptides resulted in an additive effect. Interestingly, the synergistic effects of HE2 peptides were highest with doxycycline and ciprofloxacin, antibiotics generally used to treat epididymitis. Results of this study demonstrate the potential of endogenous HE2 peptides to be pharmacologically important in designing novel strategies to treat reproductive tract infections. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.