The Chromosome-Encoded Hypothetical Protein TC0668 Is an Upper Genital Tract Pathogenicity Factor of Chlamydia muridarum
We previously associated a missense mutation of thetc0668gene of serialin vitro-passagedChlamydia muridarum, a murine model of human urogenitalC. 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 theirin vitroinfectivity, an effort was made here to isolate and characterize atc0668single mutant to determine its individual contribution to urogenital pathogenicity. Detailed genetic analysis ofC. muridarumpassages 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 ofC. muridarum in vitroremain 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 ofC. muridarumand the first with these characteristics to be discovered for aChlamydiapathogen.