Targeting of interaction between BB0323-BB0238 informs new paradigms in Lyme disease therapeutics.

ABSTRACT: Borrelia burgdorferi, one of the most prevalent tick-borne pathogens, can cause a complex and multisystem illness called Lyme disease, where there has been an unmet need for novel therapeutic or preventive strategies. We previously identified an essential protein-protein interaction (PPI) event in B. burgdorferi involving two unique proteins, BB0323 and BB0238; herein, we show that this PPI is indispensable for long-term borrelial survival in mammals and explore its potential as a novel target for small molecule therapeutics. Using X-ray crystallography, we solved the structure of the BB0238-BB0323 complex and identified the hotspot residues that form the biomolecular PPI interface area of ~1000 square Ångstroms. We then performed quantitative high-throughput drug screens of 62,740 diverse

SUBMITTER: Bista S 

PROVIDER: S-EPMC12758692 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature