# Resistance to Innate Immunity Contributes to Colonization of the Insect Gut by Yersinia pestis

## TL;DR

This study explores how Yersinia pestis survives in the gut of insects, using fruit flies to understand its interactions with the flea vector.

## Contribution

The study introduces a new fruit fly model to investigate Y. pestis gut colonization and resistance to innate immunity in insect vectors.

## Key findings

- Y. pestis establishes a stable infection in the anterior midgut of fruit fly larvae.
- PhoP and GmhA genes contribute to Y. pestis colonization and resistance to antimicrobial peptides in flies.
- OxyR mediates Y. pestis survival against reactive oxygen species in both fruit flies and fleas.

## Abstract

Yersinia pestis, the causative agent of bubonic and pneumonic plague, is typically a zoonotic vector-borne disease of wild rodents. Bacterial biofilm formation in the proventriculus of the flea contributes to chronic infection of fleas and facilitates efficient disease transmission. However prior to biofilm formation, ingested bacteria must survive within the flea midgut, and yet little is known about vector-pathogen interactions that are required for flea gut colonization. Here we establish a Drosophila melanogaster model system to gain insight into Y. pestis colonization of the insect vector. We show that Y. pestis establishes a stable infection in the anterior midgut of fly larvae, and we used this model system to study the roles of genes involved in biofilm production and/or resistance to gut immunity stressors. We find that PhoP and GmhA both contribute to colonization and resistance to antimicrobial peptides in flies, and furthermore, the data suggest biofilm formation may afford protection against antimicrobial peptides. Production of reactive oxygen species in the fly gut, as in fleas, also serves to limit bacterial infection, and OxyR mediates Y. pestis survival in both insect models. Overall, our data establish the fruit fly as an informative model to elucidate the relationship between Y. pestis and its flea vector.