Lopatto Edward D B, Santiago-Borges Jesús M, Sanick Denise A, Malladi Sameer Kumar, Azimzadeh Philippe N, Timm Morgan W, Fox Isabella F, Schmitz Aaron J, Turner Jackson S, Sayed Ahmed Shaza M, Ortinau Lillian, Gualberto Nathaniel C, Pinkner Jerome S, Dodson Karen W, Ellebedy Ali H, Kau Andrew L, Hultgren Scott J
Department of Molecular Microbiology, Washington University in St. Louis, St. Louis, MO, USA.
Center for Women's Infectious Disease Research, Washington University in St. Louis, St. Louis, MO, USA.
Sci Adv. 2025 Jun 20;11(25):eadw0698. doi: 10.1126/sciadv.adw0698.
As antimicrobial resistance increases, urinary tract infections (UTIs) are expected to pose an increased burden in morbidity and expense on the health care system, increasing the need for alternative antibiotic-sparing treatments. Most UTIs are caused by uropathogenic (UPEC), whereas causes a large 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. Three 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 by recognizing a high-affinity FimH conformation. Our data reveal that FimH mAbs hold promise as an antibiotic-sparing treatment strategy.
随着抗菌药物耐药性的增加，预计尿路感染（UTIs）将给医疗保健系统带来更高的发病负担和费用，从而增加了对替代抗生素节省治疗方法的需求。大多数尿路感染是由尿路致病性大肠杆菌（UPEC）引起的，而[具体细菌名称未给出]则导致了很大一部分非UPEC尿路感染。这两种细菌都表达带有甘露糖结合FimH黏附素的1型菌毛，这对尿路感染的发病机制至关重要。我们制备并对33种针对FimH的鼠单克隆抗体（mAbs）进行了生化特性分析。三种mAbs可保护小鼠免受[具体细菌名称未给出]尿路感染。从机制上讲，我们表明这种保护不依赖于Fc，而是由这些mAbs通过识别高亲和力FimH构象来空间位阻FimH功能的能力介导的。我们的数据表明，FimH单克隆抗体有望成为一种节省抗生素的治疗策略。
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