Antibacterial activity ofXenopsylla cheopisattacins againstYersinia pestis

Abstract

AbstractAntimicrobial peptide resistance has been proposed to play a major role in the flea-borne transmission ofYersinia pestis. However, the antimicrobial peptide response in fleas and their interaction withY. pestisis largely unknown. Attacins are one of the most abundantly expressed antimicrobial peptides within the first hours afterY. pestisinfection ofXenopsylla cheopis, a major vector of plague. In this study, we report the cloning, expression, and purification of twoX. cheopisattacin peptides and describe their interactions with and antimicrobial activities againstY. pestis. These flea attacins were shown to bind lipopolysaccharides and have potent activity againstY. pestis, however the mechanism of killing does not involve extensive membrane damage. Treatment with attacins rapidly inhibitsY. pestiscolony formation and results in oxidative stress, yet live-cell imaging revealed that bacteria continue to grow and divide for several hours in the presence of attacins before undergoing morphological changes and subsequent lysis. This data provides insights into an early battle between vector and pathogen that may impact transmission of one of the most virulent diseases known to man.