Edinburgh Napier University

  Chlamydia represents a group of Gram-negative bacteria which can infect and cause disease in a diverse range of organisms. The most well-known member of the family is Chlamydia trachomatis, the most common bacterial sexually transmitted infection across the world, which is associated with reproductive complications including infertility and miscarriage. In addition, other emerging Chlamydia-like organisms such as Waddlia chondrophila are proposed to represent a health threat, as their association with several human diseases is being investigated. As human vaccines for these infections are not currently available and antibiotic resistance may potentially risk the current treatments over the coming years, the discovery of new effective antimicrobial drugs is essential.
Cationic Host Defence Peptides (CHDPs) are known for their key role in the innate immune response. In mammals, there are two main families of CHDPs, cathelicidins and defensins. These peptides have been identified in several different cell types including epithelial cells, macrophages and neutrophils among others. The human cathelicidin, LL-37, displays broad spectrum antimicrobial and immunomodulatory potential following proteolytic cleavage from the precursor molecule hCAP-18. In addition to their direct antimicrobial activity, cathelicidins have been shown to influence the inflammatory response to pathogens and to play a role in wound repair and immune cell recruitment and differentiation. As such, they represent exciting prospects for the development of novel peptide-based therapeutics for a range of infections.
This study investigated the activity of cathelicidins from humans and animals against different Chlamydia and Waddlia chondrophila, assessing changes in bacterial population as well as immunomodulatory effects on the epithelial host cell line, HEp2, during infection. Our results show that cathelicidins can have a direct effect on Chlamydia populations and that the effect is most visible when the pathogen is directly exposed to the peptide. We demonstrate that cathelicidins can directly modulate the host cell response to these infections, likely through direct inhibition of the pathogen induced inflammatory response, rather than by modulation of host cell death pathways. Furthermore, we demonstrate that the emerging pathogen Waddlia chondrophila appears to show intrinsic resistance to the activity of these peptides, potentially representing a concerning trait of this organism in terms of innate immune evasion.