# LAP-Hsp60 complex modulates epithelial tight junction barrier

## TL;DR

A protein complex helps bacteria cross the intestinal barrier without causing harm, offering a new way to deliver medicines through the gut.

## Contribution

The LAP-Hsp60 complex is identified as a novel tight junction modulator for safe and effective drug delivery.

## Key findings

- LAP forms multimeric structures and interacts with Hsp60 to modulate tight junctions.
- LAP enables drug absorption across the intestinal barrier without inflammation.
- LAP or its mimetics could improve oral delivery of biologics.

## Abstract

During infection, Listeria adhesion protein (LAP), a housekeeping enzyme, acts as a tight junction modulator (TJM) through interaction with Hsp60 to facilitate Listeria monocytogenes translocation across the intestinal epithelial barrier. Here, we used purified LAP as a potential TJM to overcome the limiting and variable effects observed by other agents in the class. We structurally determined the LAP interaction alone and in complex with Hsp60 utilizing cryo-EM and computational analysis. LAP structure resolved at 2.83 Å, forms multimeric interlocking dimers and tetramers, and the N-domain interacts with Hsp60, while the C-domain bridges bacterial surface receptor InlB. The structural studies complement LAP-mediated cyclic peptide drugs (vancomycin and desmopressin) absorption across the intestinal barrier in a mouse model without inducing inflammation or adverse effects on the TJ architecture. This study demonstrates that the LAP-Hsp60 complex is the basis for downstream utilization of LAP or peptide mimetics as promising TJM for improved peroral biologics delivery.