title: Plasmid-encoded Pgp3 is a major virulence factor for Chlamydia muridarum to induce hydrosalpinx in mice.
abstract: Hydrosalpinx induction in mice by Chlamydia muridarum infection, a model that has been used to study C. trachomatis pathogenesis in women, is known to depend on the cryptic plasmid that encodes eight genes designated pgp1 to pgp8. To identify the plasmid-encoded pathogenic determinants, we evaluated C. muridarum transformants deficient in the plasmid-borne gene pgp3, -4, or -7 for induction of hydrosalpinx. C. muridarum transformants with an in-frame deletion of either pgp3 or -4 but not -7 failed to induce hydrosalpinx. The deletion mutant phenotype was reproduced by using transformants with premature termination codon insertions in the corresponding pgp genes (to minimize polar effects inherent in the deletion mutants). Pgp4 is known to regulate pgp3 expression, while lack of Pgp3 does not significantly affect Pgp4 function. Thus, we conclude that Pgp3 is an effector virulence factor and that lack of Pgp3 may be responsible for the attenuation in C. muridarum pathogenicity described above. This attenuated pathogenicity was further correlated with a rapid decrease in chlamydial survival in the lower genital tract and reduced ascension to the upper genital tract in mice infected with C. muridarum deficient in Pgp3 but not Pgp7. The Pgp3-deficient C. muridarum organisms were also less invasive when delivered directly to the oviduct on day 7 after inoculation. These observations demonstrate that plasmid-encoded Pgp3 is required for C. muridarum survival in the mouse genital tract and represents a major virulence factor in C. muridarum pathogenesis in mice.
authors.affiliation: Department of Microbiology & Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Department of Dermatovenereology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
authors.forename: Yuanjun
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Microbiology & Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Yumeng
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Microbiology & Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Zhangsheng
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Key Laboratory of Hormones and Development (Ministry of Health), Metabolic Diseases Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, People's Republic of China.
authors.forename: Yina
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Microbiology & Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Siqi
authors.initials: S
authors.lastname: Gong
authors.affiliation: Department of Dermatovenereology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Hou
authors.affiliation: Department of Microbiology and Immunology, University of South China, Hengyang, Hunan, People's Republic of China.
authors.forename: Chaoqun
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Microbiology and Immunology, University of South China, Hengyang, Hunan, People's Republic of China.
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Dermatovenereology, Tianjin Medical University General Hospital, Tianjin, People's Republic of China.
authors.forename: Quanzhong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Microbiology and Immunology, University of South China, Hengyang, Hunan, People's Republic of China.
authors.forename: Yimou
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Microbiology & Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Baseman
authors.affiliation: Department of Microbiology & Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Zhongg@uthscsa.edu.
authors.forename: Guangming
authors.initials: G
authors.lastname: Zhong
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002690:Chlamydia Infections / Q000382:microbiology / Q000473:pathology*; D023502:Chlamydia muridarum / Q000235:genetics / Q000472:pathogenicity*; D004195:Disease Models, Animal; D005184:Fallopian Tube Diseases / Q000382:microbiology* / Q000473:pathology*; D005260:Female; D006367:HeLa Cells; D006801:Humans; D008809:Mice, Inbred C3H; D010957:Plasmids; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D037521:Virulence Factors; C082169:pgp3 protein, Chlamydia