Monoclonal Antibodies Targeting the FimH Adhesin Protect Against Uropathogenic UTI

Overview

Journal bioRxiv

Date 2024 Dec 23

PMID 39713358

Authors

Edward D B Lopatto

Jesus M Santiago-Borges

Denise A Sanick

Sameer Kumar Malladi

Philippe N Azimzadeh

Morgan W Timm

Isabella F Fox

Aaron J Schmitz

Jackson S Turner

Shaza Sayed Ahmed

Lillian Ortinau

Nathaniel C Gualberto

Jerome S Pinkner

Karen W Dodson

Ali H Ellebedy

Andrew L Kau

Scott J Hultgren

Affiliations

Soon will be listed here.

Abstract

As antimicrobial resistance increases, urinary tract infections (UTIs) are expected to pose an increased burden in morbidity and expense on the healthcare system, increasing the need for alternative antibiotic-sparing treatments. Most UTIs are caused by uropathogenic (UPEC), while causes a significant portion of non-UPEC UTIs. Both bacteria express type 1 pili tipped with the mannose-binding FimH adhesin critical for UTI pathogenesis. We generated and biochemically characterized 33 murine monoclonal antibodies (mAbs) to FimH. Two mAbs protected mice from UTI. Mechanistically, we show that this protection is Fc-independent and mediated by the ability of these mAbs to sterically block FimH function. Our data reveals that FimH mAbs hold promise as an antibiotic-sparing treatment strategy.

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