# Infectivity of a pathogenicity-attenuated Chlamydia muridarum mutant in the genital tract

## TL;DR

A modified Chlamydia strain called intrOv shows reduced ability to infect the genital tract, making it a potential safe oral vaccine candidate.

## Contribution

The study identifies intrOv's delayed infection and reduced epithelial cell invasion as factors contributing to its pathogenicity attenuation.

## Key findings

- Few live intrOv organisms were recovered from the genital tract early after intravaginal infection.
- IntrOv showed reduced invasion of epithelial cells but normal intracellular replication.
- IntrOv's pathogenicity attenuation correlates with delayed infection and reduced epithelial cell invasion.

## Abstract

A Chlamydia muridarum mutant designated as intrOv was evaluated as an intracellular oral vaccine vector 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.