# Protein tyrosine phosphatase PTP1B is a positive regulator of the intracellular development of Chlamydia trachomatis

## TL;DR

This study shows that the host protein PTP1B helps the bacteria Chlamydia trachomatis grow inside cells, highlighting a new role for host phosphatases in bacterial infections.

## Contribution

The study identifies PTP1B as a novel host phosphatase that positively regulates Chlamydia trachomatis intracellular development.

## Key findings

- PTP1B promotes inclusion development and increases infectious elementary body production by Chlamydia.
- PTP1B inhibition reduces inclusion size and bacterial infectivity without affecting invasion efficiency.
- PTP1B can dephosphorylate the chlamydial effector Tarp but does not significantly alter its phosphorylation during infection.

## Abstract

The intracellular survival and replication of Chlamydia trachomatis rely on the precise manipulation of host signaling pathways. Host kinases are instrumental in the modulation of host signaling during C. trachomatis infection. However, the potential contribution of host phosphatases to chlamydial pathogenesis remains poorly understood. Here, we identified the host tyrosine phosphatase PTP1B as a positive regulator of C. trachomatis intracellular development. Gain-of-function approaches revealed that PTP1B promotes inclusion development and increases the production of infectious elementary bodies, whereas loss-of-function by chemical inhibition or silencing leads to a reduction in both inclusion size and bacterial infectivity. Interestingly, PTP1B inhibition did not affect Chlamydia trachomatis invasion efficiency, suggesting a specific role during the developmental phase of the chlamydial life cycle. To explore the functional relevance of PTP1B and its potential interaction with chlamydial effectors, we focused on the early-secreted effector Tarp, which undergoes tyrosine phosphorylation upon host cell entry. In vitro biochemical assays demonstrated that recombinant PTP1B can dephosphorylate both native and recombinant forms of Tarp. However, PTP1B inhibition during infection did not significantly alter Tarp phosphorylation levels, possibly owing to the overpowering influence of host tyrosine kinases. These findings suggest that while Tarp may not be a major physiological substrate, PTP1B is capable of interacting with phosphorylated chlamydial effectors. Together, these results establish PTP1B as a host factor that supports chlamydial development and underscore the underappreciated role of host phosphatases in bacterial pathogenesis. This study provides a foundation for future work exploring phosphatase-mediated regulation of infection and potential host-directed therapeutic strategies.