# Nuclear Localization of Effector BPE159: A Pivotal Mechanism for Intracellular Persistence of Brucella by Hampering Host Autophagy

## TL;DR

This study reveals how a Brucella protein, BPE159, helps the bacteria survive in host cells by blocking the host's autophagy process.

## Contribution

The novel finding is that BPE159 localizes to the host nucleus and interacts with Eci1 to inhibit autophagy, promoting bacterial persistence.

## Key findings

- BPE159 localizes in the nucleus and interacts with host protein Eci1.
- BPE159 inhibits macrophage autophagy by downregulating autophagy-related genes.
- BPE159 enables Brucella persistence by hampering host autophagy.

## Abstract

Brucella is a neglected foodborne pathogen, which contaminates milk, dairy products, meat, and meat products of infected animals. However, the role of the Brucella putative effector (BPE) protein family, which relies on the type IV secretion system (T4SS) in Brucella abortus, remains unclear. We demonstrated that BPE159 mediates the regulation of host nuclei in autophagy. The host-interacting protein Eci1 was screened using yeast two-hybridization, molecular docking, and immunoprecipitation, and BPE159-deleted (ΔBPE159) and complementary (ΔBPE159-C) strains were constructed by homologous recombination. We evaluated their growth, survival, and replication and measured the expression of autophagy-related cytokine mRNAs in macrophages. BPE159 was localized in the nucleus of host cells and interacted with Eci1 to downregulate the expression of macrophage autophagy factors, thereby inhibiting host autophagy and enabling the persistence of Brucella. These findings highlight the critical role of BPE159 in mediating autophagy through Eci1 in host cells to promote Brucella survival in host cells.