Infectivity of a pathogenicity-attenuated <i>Chlamydia muridarum</i> mutant in the genital tract

A <i>Chlamydia muridarum</i> mutant designated as intrOv was evaluated as an <i>intr</i>acellular <i>o</i>ral vaccine <i>v</i>ector because it can induce protection in the genital tract following oral inoculation but does not elicit genital pathology following intravaginal infection. However, the mechanism of intrOv's attenuation is unclear. Here, we report that few live organisms were recovered from vaginal swabs during the early stage of intrOv intravaginal infection in mice. At a low inoculating dose, an isogenic wild-type control strain established a productive infection, while intrOv failed to do so. Although a higher inoculating dose allowed intrOv and its control to productively infect mice, fewer live intrOv than the control organisms were recovered from the lower genital tract tissues on day 3 post-infection. By day 7, animals infected with intrOv or the control shed similar numbers of live organisms, suggesting that intrOv's deficiency on day 3 was transient. Consistently, intrOv reduced invasion of epithelial cells but maintained as robust intracellular replication as its control. Our results correlate intrOv's delay in infecting the lower genital tissues and reduction in invading epithelial cells with its attenuation in genital pathogenicity, laying the foundation for further revealing the mechanisms of intrOv's attenuation in pathogenicity during genital tract infection.