AUTHOR=Huang Yumeng , Wu Haoqing , Sun Yina , Liu Yuanjun 

TITLE=Tryptophan residue of plasmid-encoded Pgp3 is important for Chlamydia muridarum to induce hydrosalpinx in mice

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1216372

DOI=10.3389/fmicb.2023.1216372

ISSN=1664-302X

ABSTRACT=<p>The crucial role of plasmid-encoded protein Pgp3 in <italic>Chlamydia</italic> pathogenesis has been demonstrated in various animal models. Previous studies have revealed that the Pgp3-deficient <italic>C. muridarum</italic> mutant fails to induce hydrosalpinx after vaginal inoculation in mice. Structural analysis of <italic>C. trachomatis</italic> Pgp3 trimer has indicated that Trp234 may play a critical role in trimeric crystal packing interactions and that Tyr197 is involved at predominant cation-binding sites. In this study, we constructed <italic>C. muridarum</italic> transformants harboring Pgp3, Trp234, or Tyr197 point mutations (Pgp3W234A and Pgp3Y197A). C3H/HeJ mice infected with Pgp3W234A mutant failed to induce severe hydrosalpinx in the oviduct tissue, which largely phenocopied the full-length Pgp3-deficient <italic>C. muridarum</italic>. The Pgp3Y197A variant induced an intermediate severity of pathology. The attenuated pathogenicity caused by the Pgp3W234A mutant may be due to its decreased survival in the lower genital tracts of mice, reduced ascension to the oviduct, and milder induction of inflammatory cell infiltration in the oviduct tissue. Thus, our results point to an important amino acid residue involved in Pgp3 virulence, providing a potential therapeutic target for chlamydial infection.</p>