Журнал исследований иммунологии слизистой оболочки

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PGP3 is a Chlamydial Plasmid-Encoded Virulence Factor

Shuping Hou and Guangming Zhong

Sexually transmitted infections with Chlamydia can lead ectopic pregnancy and tubal infertility. However, the precise pathogenic mechanisms remain unclear. The chlamydial cryptic plasmid is known to play a critical role in chlamydial pathogenesis in the genital tract. C. muridarum depleted of plasmid or deficient in the plasmid-encoded pGP3 protein was highly attenuated in ascending infection and inducing upper genital tract pathology, demonstrating that the plasmid-encoded pGP3 is a key virulence factor. pGP3 was found to neutralize the antichlamydial activity of the host antimicrobial peptides particularly the cathelicidin peptide LL-37 (human) or CRAMP (mice). This pGP3- mediated neutralization was dependent on Pgp3 to form stable complexes with LL-37. The complex formation was further mapped to the middle domain of pGP3. These observations suggest that Chlamydia may secrete Pgp3 for trapping antimicrobial peptides during chlamydial spreading from cell to cell in the genital tract mucosal tissue. The tertial structure of pGP3 reveals that pGP3 may also directly participate in the induction of tubal inflammation by activating TNF signaling pathway. Finally, pGP3 was recently reported to be essential for chlamydial colonization in the gastrointestinal tract. Thus, careful analyses of pGP3 functionality may reveal novel information on how Chlamydia interacts with its host and induces pathologies in the upper genital tract.