Bacterial Evasion of Host‐Derived Antimicrobial Peptides on Mucosal Surfaces

The small antimicrobial peptides found in phagocytic cells, epithelial cells, and on mucosal surfaces and their mechanisms of antimicrobial killing have been reviewed recently. The chapter summarizes them as background for discussing the numerous strategies that microorganisms use to avoid being killed by them. This is an exciting area of research. Identification of mechanisms for resistance to antimicrobial peptides can provide insight as to how microorganisms interact with the innate immune system to either produce progressive infection or enter into commensal, latency, or carrier states. In the early 1980s, Hans Boman and Robert Lehrer independently isolated and purified the first families of insect cecropins and mammalian defensins, respectively. Larger antimicrobial proteins have been fragmented experimentally into smaller peptides to search for the smallest sequence representing the antimicrobial domain. Many pathogenic organisms are susceptible in vitro to antimicrobial peptides, but in vivo can exist in environments containing the same concentrations of antimicrobial peptides. Rapid penetration of epithelial cells reduces the time of contact between microorganisms and antimicrobial peptides in mucosal secretions. Direct adaptation by gram-negative and gram-positive microorganisms to become resistant in an environment containing antimicrobial peptides is the most characterized strategy. A variety of nonimmune and immune mechanisms have evolved at mucosal surfaces to prevent microbial invasion and damage. Predominant among the nonimmune mechanisms is the presence of a multiple peptide-containing constitutive and inducible antimicrobial barrier in the granules of phagocytes and mucosal fluids.