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ABSTRACT Mucins are glycoproteins which can be found in host cell membranes and as a gelatinous surface formed from secreted mucins. Mucosal surfaces in mammals form a barrier to invasive microbes, particularly bacteria, but are a point of attachment for others.Clostridioides difficileis an anaerobic bacterium, which colonizes the mammalian gastrointestinal (GI) tract and is a common cause of acute GI inflammation leading to a variety of negative outcomes. AlthoughC. difficiletoxicity stems from secreted toxins, colonization is a prerequisite forC. difficiledisease. WhileC. difficileis known to associate with the mucous layer and underlying epithelium, the mechanisms underlying these interactions that facilitate colonization are less well understood. To understand the molecular mechanisms by whichC. difficileinteracts with mucins, we usedex vivomucosal surfaces to test the ability ofC. difficileto bind to mucins from different mammalian tissues. We found significant differences inC. difficileadhesion based upon the source of mucins, with highest levels of binding observed to mucins purified from the human colonic adenocarcinoma line LS174T and lowest levels of binding to porcine gastric mucin. We also observed defects in adhesion by mutants deficient in flagella but not type IV pili. These results imply that interactions between host mucins andC. difficileflagella facilitate the initial host attachment ofC. difficileto host cells and secreted mucus. IMPORTANCEClostridioides difficileis one of the leading causes of hospital-acquired infections worldwide and presents challenges in treatment due to recurrent gastrointestinal disease after treatment with antimicrobials. The mechanisms by whichC. difficilecolonizes the gut represent a key gap in knowledge, including its association with host cells and mucosa. Our results show the importance of flagellin for specific adhesion to mucosal hydrogels and can help to explain prior observations of adhesive defects in flagellin and pilin mutants. 

Abstract The colonization of biomedical surfaces by bacterial biofilms is concerning because these microorganisms display higher antimicrobial resistance in biofilms than in liquid cultures. Developing antimicrobial coatings that can be easily applied to medically‐relevant complex‐shaped objects, such as implants and surgical instruments, is an important and challenging research direction. This work reports the preparation of antibacterial surfaces via the electrodeposition of a conformal hydrogel of self‐assembling cationic peptide‐amphiphiles (PAs). Hydrogels of three PAs are electrodeposited: C₁₆K₂, C₁₆K₃, and C₁₈K₂, where C_nis an alkyl chain ofnmethylene groups and K_mis an oligopeptide ofmlysines. The processing variables (electrodeposition time, potential, pH, salt concentration, agitation) enable fine control of film thickness, demonstrating the flexibility of the method and allowing to unravel the mechanisms underlying electrodeposition. The electrochemically prepared hydrogels inhibit the growth ofStaphylococcus aureus,Escherichia coli, andPseudomonas aeruginosain agar plates, and prevent the formation of biofilms ofAcinetobacter baumanniiandP. aeruginosaand the formation ofA. baumanniicolonies in solid media. C₁₆K₂and C₁₆K₃hydrogels outperform the antimicrobial activity of those of C₁₈K₂while maintaining good compatibility with human cells. 

C. difficile infection (CDI) is a costly and increasing burden on the healthcare systems of many 11 developed countries due to the high rates of nosocomial infections. Despite the availability of 12 several antibiotics with high response rates, effective treatment is hampered by recurrent 13 infections. One potential mechanism for recurrence is the existence of C. difficile biofilms in the 14 gut which persist through the course of antibiotics. In this review, we describe current 15 developments in understanding the molecular mechanisms by which C. difficile biofilms form 16 and are stabilized through extracellular biomolecular interactions. 

Acinetobacterinfections are a growing burden on health care systems worldwide due to increasing antimicrobial resistance through multiple mechanisms. Biofilm formation is an established mechanism of antimicrobial resistance, and its inhibition has the potential to potentiate the use of existing drugs against pathogenicAcinetobacter.