# The N-terminus of the Chlamydia trachomatis effector Tarp engages the host Hippo pathway

## TL;DR

This study shows that the N-terminal region of the Chlamydia effector Tarp can manipulate the host Hippo pathway to promote cell survival during infection.

## Contribution

The study identifies a novel function of the N-terminal region of Tarp in modulating the Hippo signaling pathway in vivo.

## Key findings

- N-Tarp causes wing disc overgrowth and increased adult wing size in Drosophila, similar to Yorkie overexpression.
- N-Tarp upregulates Hippo target genes and its effects can be rescued by reducing Yorkie or its targets.
- The N-terminal region of Tarp alters Hippo signaling and acts upstream of Yorkie in Drosophila.

## Abstract

Chlamydia trachomatis (Ct) is an obligate, intracellular Gram-negative bacteria and the leading bacterial sexually transmitted infection in the United States. Chlamydia manipulates the host cell biology using various secreted bacterial effectors during its intracellular development. The early effector translocated actin-recruiting phosphoprotein (Tarp), important for Chlamydia entry, has a well-characterized C-terminal region which can polymerize and bundle F-actin. In contrast, not much is known about the function of the N-terminus of Tarp (N-Tarp), though present in many Chlamydia spp. To address this, we use Drosophila melanogaster as an in vivo cell biology platform to study N-Tarp-host interactions. Transgenic expression of N-Tarp in Drosophila results in developmental phenotypes consistent with altered host Salvador-Warts-Hippo signaling, a conserved signaling cascade that regulates host cell proliferation and survival. We studied the N-Tarp function in larval imaginal wing discs, which are sensitive to perturbations in Hippo signaling. N-Tarp causes wing disc overgrowth and a concomitant increase in adult wing size, phenocopying overexpression of the Hippo co-activator Yorkie. N-Tarp also causes upregulation of Hippo target genes. Last, N-Tarp-induced phenotypes can be rescued by reducing the levels of Yorkie or the Hippo target genes CycE and Drosophila inhibitor of apoptosis 1 (Diap1). Thus, we provide evidence that the N-terminal region of the Chlamydia effector Tarp is sufficient to alter host Hippo signaling and acts upstream of the co-activator Yorkie.

The survival of obligate intracellular bacteria like Chlamydia depends on the survival of the host cell itself. It is not surprising that Chlamydia-infected cells are resistant to cell death, though the exact molecular mechanism is largely unknown. Here, we establish that the N-terminal region of the well-known Ct early effector Tarp can alter Hippo signaling in vivo. Only recently implicated in Chlamydia infection, the Hippo pathway is known to promote cell survival. Our findings illuminate one possible mechanism for Chlamydia to promote host cell survival during infection. We further demonstrate the utility of Drosophila melanogaster as a tool in the study of effector function.