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Synthetic polymers active against Clostridium difficile vegetative cell growth and spore outgrowth.

Liu R, Suárez JM, Weisblum B, Gellman SH, McBride SM - J. Am. Chem. Soc. (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and ‡Department of Medicine, University of Wisconsin , Madison, Wisconsin 53706, United States.

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.

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Hemolyticprofiles of selected nylon-3 polymers and antimicrobials.
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fig4: Hemolyticprofiles of selected nylon-3 polymers and antimicrobials.

Mentions: HDPs and HDP-mimetic polymersare thought to exert antibacterial effects via disruption ofmembrane barrier function. Therefore, prokaryotic vs eukaryotic cellselectivity is often assessed by determining whether an agent thatexerts antibacterial activity also causes disruption of humanred blood cell (hRBC) membranes (“hemolysis”). As shownin Figure 4, the three nylon-3 copolymers andthe three comparison compounds display varied hemolytic activities;the data for the polymers are consistent with previously reportedresults.43 Host-defense peptide LL-37 andpolymer 50:50 DM:CH both display significant hemolytic activity. Incontrast, 50:50 DM:TM causes very little hemolysis at the MIC/OICand only mild hemolysis at high concentrations (400 μg/mL).Thus, 50:50 DM:TM manifests the most favorable activity profile amongthe materials we have evaluated, since this non-hemolytic polymeris quite active against both C. difficile strainsin terms of inhibiting vegetative cell growth and spore outgrowth.


Synthetic polymers active against Clostridium difficile vegetative cell growth and spore outgrowth.

Liu R, Suárez JM, Weisblum B, Gellman SH, McBride SM - J. Am. Chem. Soc. (2014)

Hemolyticprofiles of selected nylon-3 polymers and antimicrobials.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4210120&req=5

fig4: Hemolyticprofiles of selected nylon-3 polymers and antimicrobials.
Mentions: HDPs and HDP-mimetic polymersare thought to exert antibacterial effects via disruption ofmembrane barrier function. Therefore, prokaryotic vs eukaryotic cellselectivity is often assessed by determining whether an agent thatexerts antibacterial activity also causes disruption of humanred blood cell (hRBC) membranes (“hemolysis”). As shownin Figure 4, the three nylon-3 copolymers andthe three comparison compounds display varied hemolytic activities;the data for the polymers are consistent with previously reportedresults.43 Host-defense peptide LL-37 andpolymer 50:50 DM:CH both display significant hemolytic activity. Incontrast, 50:50 DM:TM causes very little hemolysis at the MIC/OICand only mild hemolysis at high concentrations (400 μg/mL).Thus, 50:50 DM:TM manifests the most favorable activity profile amongthe materials we have evaluated, since this non-hemolytic polymeris quite active against both C. difficile strainsin terms of inhibiting vegetative cell growth and spore outgrowth.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and ‡Department of Medicine, University of Wisconsin , Madison, Wisconsin 53706, United States.

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.

Show MeSH
Related in: MedlinePlus