Antimicrobial peptides in defence of the oral and respiratory tracts

Antimicrobial peptides (AMPs) are components of complex host secretions, acting synergistically with other innate defence molecules to combat infection and control resident microbial populations throughout the oral cavity and respiratory tract. AMPs are directly antimicrobial, bind lipopolysaccharide (LPS) and lipoteichoic acid, and are immunomodulatory signals. Pathogenic and commensal organisms display a variety of resistance mechanisms, which are related to structure of cell wall components (e.g. LPS) and cytoplasmic membranes, and peptide breakdown mechanisms. For example, LPS of the AMP-resistant cystic fibrosis pathogen Burkholderia cepacia is under-phosphorylated and highly substituted with charge-neutralising 4-deoxy-4-aminoarabinose. Additionally, host mimicry by addition of phosphorylcholine contributes to resistance in oral and respiratory organisms. Porphyromonas gingivalis, Pseudomonas aeruginosa and other pathogens produce extracellular and membrane-bound proteases that degrade AMPs. Many of these bacterial properties are environmentally regulated. Their modulation in response to host defences and inflammation can result in altered sensitivity to AMPs, and may additionally change other host-microbe interactions, e.g. binding to Toll-like receptors. The diversity and breadth of antimicrobial cover and immunomodulatory function provided by AMPs is central to the ability of a host to respond to the diverse and highly adaptable organisms colonising oral and respiratory mucosa.