The chromosome-encoded hypothetical protein TC0668 is an upper genital tract pathogenicity factor of Chlamydia muridarum

Turner Allen Conrad, Siqi Gong, Zhangsheng Yang, Patrick Matulich, Jonathon Keck, Noah Beltrami, Chaoqun Chen, Zhou Zhou, Jin Dai, Guangming Zhong

Research output: Contribution to journalArticle

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Abstract

We previously associated a missense mutation of the tc0668 gene of serial in vitro-passaged Chlamydia muridarum, a murine model of human urogenital C. trachomatis, with severely attenuated disease development in the upper genital tract of female mice. Since these mutants also contained a TC0237 Q117E missense mutation that enhances their in vitro infectivity, an effort was made here to isolate and characterize a tc0668 single mutant to determine its individual contribution to urogenital pathogenicity. Detailed genetic analysis of C. muridarum passages revealed a truncated variant with a G216* nonsense mutation of the 408-amino-acid TC0668 protein that does not produce a detectable product. Intracellular growth and infectivity of C. muridarum in vitro remain unaffected in the absence of TC0668. Intravaginal inoculation of the TC0668 null mutant into C3H/HeJ mice results in a typical course of lower genital tract infection but, unlike a pathogenic isogenic control, is unable to elicit significant chronic inflammation of the oviduct and fails to induce hydrosalpinx. Thus, TC0668 is demonstrated as an important chromosome- encoded urogenital pathogenicity factor of C. muridarum and the first with these characteristics to be discovered for a Chlamydia pathogen.

Original languageEnglish (US)
Pages (from-to)467-479
Number of pages13
JournalInfection and Immunity
Volume84
Issue number2
DOIs
StatePublished - 2015

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ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Conrad, T. A., Gong, S., Yang, Z., Matulich, P., Keck, J., Beltrami, N., Chen, C., Zhou, Z., Dai, J., & Zhong, G. (2015). The chromosome-encoded hypothetical protein TC0668 is an upper genital tract pathogenicity factor of Chlamydia muridarum. Infection and Immunity, 84(2), 467-479. https://doi.org/10.1128/IAI.01171-15