Type 1 fimbrial protein FimH of Enterobacteriaceae-a promising target to mitigate different infections

Gram-negative bacterial infections are increasingly becoming resistant to available antibiotic treatment options. The World Health Organization attributed over 1 million deaths to bacterial antimicrobial resistance (AMR) in 2021. While there is a crisis in terms of the available effective antibiotic repertoire, there is also a simultaneous decline in novel drug discovery. In this scenario, the search for alternative or complementary therapeutic options is not only relevant, but also urgently needed. Bacterial virulence factors have been proposed as alternative therapeutic targets since there is lesser propensity for emergence of resistance to these effector molecules. Type 1 fimbriae or FimH of Enterobacteriaceae constitute such a potential target, as these structures are crucial for the initial adhesion and colonization by binding mannose-rich host cell-surface receptors. Additionally, FimH has been associated with multiple diseases, including urinary tract infections (UTIs) and Crohn's disease (CD). The elucidation of Escherichia coli FimH crystal structure has opened the possibility for structure-based drug design to combat these diseases. Many mannose-based compounds are being tried as alternative therapeutics against UTIs and CD with a few molecules showing promise. In this review, we discuss the role of FimH in different diseases, its potential and scope for structure-based development of different mannose-based compounds, and other advanced FimH-blocking therapeutics in preventing these infections.