The Structural Integrity of Plasmid-Encoded Pgp3 Is Essential for Induction of Hydrosalpinx by Chlamydia muridarum

Pgp3 consists of globular N- and C-terminal domains connected by a triple-helical coiled-coil middle domain. We demonstrated previously that Pgp3 is required for induction of hydrosalpinx by Chlamydia muridarum. We constructed C. muridarum transformants harboring deletion of the Pgp3 N-terminus (pgp3 Delta n), C-terminus (pgp3 Delta c), ormiddle domain (pgp3 Delta m). C3H/HeJ and CBA/Jmice infected with pgp3 Delta n or pgp3 Delta m failed to induce hydrosalpinx in oviduct tissue. However, the pgp3 Delta c transformant induced mild hydrosalpinx in 20% of C3H/HeJ mice (severity score 0.2 +/- 0.6) and in 40% of CBA/Jmice (severity score 0.8 +/- 1.3). The attenuated pathogenicity of the transformants harboring Pgp3 domain deletions was correlated with impaired in vitro growth and significantly reduced infectivity in the mouse lower genital tract. Moreover, the oviduct tissue of C3H/HeJ and CBA/J mice infected with the Pgp3-domain-deficient transformants displayed less inflammatory cell infiltration. Thus, the structural integrity of plasmid-encoded Pgp3 is essential for induction of hydrosalpinx by C. muridarum.