Antibacterial activity of antimicrobial peptide PMAP-36 combined with tetracycline against porcine extraintestinal pathogenic Escherichia coli in vitro and in vivo

Abstract The increased emergence of antimicrobial resistance brings great challenges in controlling porcine extraintestinal pathogenic Escherichia coli(ExPEC) infections. Combinations of antimicrobial peptides (AMPs) and antibiotics can synergistically improve antimicrobial efficacy and reduce bacterial resistance. This study investigated the antibacterial activity of porcine myeloid antimicrobial peptide 36 (PMAP-36) in combination with tetracycline against porcine ExPEC PCN033 both in vitroand in vivo. We found that the MBCs of AMPs (PMAP-36 and PR-39) against ExPEC strains PCN033 and RS218 were 10 μM and 5 μM, respectively. PMAP-36 and antibiotics (tetracycline, gentamicin) had a synergistic bactericidal effect against PCN033. PMAP-36 delayed the emergence of PCN033 resistance to tetracycline. The treatment of PMAP-36 combined with tetracycline significantly increased survival and reduced bacterial load as well as decreasing inflammatory response in mice. In addition, the combination of PMAP-36 and tetracycline promoted the migration of monocytes/macrophages to the infection site. Our results suggest that AMPs in combination with antibiotics may provide more therapeutic options against multi-drug resistant porcine ExPEC.