Susceptibility ofChlamydia trachomatisto Protegrins and Defensins

We compared the susceptibilities of Chlamydia trachomatis elementary bodies (EBs) to human defensin HNP-2 and porcine protegrin PG-1, cysteine-rich beta-sheet antimicrobial peptides produced by mammalian leukocytes. Although both peptides protected McCoy cell monolayers from infection by chlamydial EBs, protegrins were especially potent. Protegrin-mediated inactivation of chlamydiae occurred rapidly, was relatively independent of the presence of serum, and was effective against serovars L2, D, and H. Protegrin-treated EBs showed striking morphological changes, with obvious damage to their limiting membranes and loss of their cytoplasmic contents and nucleoid. Their effectiveness against chlamydial EBs and other sexually transmitted pathogens combined with their relative lack of cytotoxicity suggests that protegrins and related molecules could serve as prototypes for topical agents to prevent sexually transmitted chlamydial infection. Chlamydia trachomatis, a gram-negative eubacterial obligate intracellular pathogen, causes a number of human diseases, including trachoma and genitourinary tract infections that oftenresultinsterility(21).Chlamydiaehaveauniquedimorphic growth cycle that allows their survival in two discontinuous habitats. Within eukaryotic host cells, Chlamydiae form inclusions and reorganize to a noninfectious reticulate body. These reticulate bodies eventually undergo nucleoid condensation and other changes to form releasable elementary bodies (EBs) that can survive the extracellular environment and infect other cells. Although their inner and outer membranes define a periplasmicspace,Chlamydiaedifferfromothergram-negative bacteria by lacking peptidoglycan (2). The outer membrane of chlamydiae contains several cysteine-rich proteins, including a