title: Synthetic polymers active against Clostridium difficile vegetative cell growth and spore outgrowth.
abstract: Nylon-3 polymers (poly-β-peptides) have been investigated as synthetic mimics of host-defense peptides in recent years. These polymers are attractive because they are much easier to synthesize than are the peptides themselves, and the polymers resist proteolysis. Here we describe in vitro analysis of selected nylon-3 copolymers against Clostridium difficile, an important nosocomial pathogen that causes highly infectious diarrheal disease. The best polymers match the human host-defense peptide LL-37 in blocking vegetative cell growth and inhibiting spore outgrowth. The polymers and LL-37 were effective against both the epidemic 027 ribotype and the 012 ribotype. In contrast, neither vancomycin nor nisin inhibited outgrowth for the 012 ribotype. The best polymer was less hemolytic than LL-37. Overall, these findings suggest that nylon-3 copolymers may be useful for combatting C. difficle.
authors.affiliation: Department of Chemistry and ‡Department of Medicine, University of Wisconsin , Madison, Wisconsin 53706, United States.
authors.forename: Runhui
authors.initials: R
authors.lastname: Liu
authors.forename: Jose M
authors.initials: JM
authors.lastname: Suárez
authors.forename: Bernard
authors.initials: B
authors.lastname: Weisblum
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Gellman
authors.forename: Shonna M
authors.initials: SM
authors.lastname: McBride
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001409:Bacillus cereus / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016360:Clostridioides difficile / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D004305:Dose-Response Relationship, Drug; D016984:Enterococcus faecium / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship; D020713:Vancomycin Resistance / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D010455:Peptides; D011108:Polymers