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Bacterial pili and fimbriae are hair-like proteinaceous appendages extending from the surface of Gram-negative bacteria, serving as critical virulence factors in multidrug-resistant (MDR) pathogens (Busch & Waksman, 2012). These structures primarily function as adhesins, mediating the specific attachment of bacteria to host cell receptors, which is the essential first step for colonization and infection (Sauer et al., 2000). In pathogens such as uropathogenic Escherichia coli (UPEC) and Klebsiella pneumoniae, pili facilitate the formation of biofilms and the invasion of host tissues, protecting the bacteria from the immune system and antibiotic treatment (Totsika, 2017). Because these structures are vital for pathogenesis but not for bacterial survival, they are considered high-priority targets for anti-adhesion therapies (Spaulding et al., 2017). Therapeutic agents like mannosides (e.g., sibofimloc) and pilicides are designed to competitively inhibit adhesin binding or disrupt the assembly of the pili via the chaperone-usher pathway (Enterome, 2018). This anti-virulence strategy aims to disarm pathogens without exerting the strong selective pressure for resistance associated with traditional bactericidal antibiotics.
Inhibition of bacterial adhesion to host cells by competitively binding to fimbrial adhesins (e.g., FimH) or disrupting the assembly of pili via the chaperone-usher pathway, thereby preventing colonization and biofilm formation.
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