Nylon-3 Polymers Active against Drug-Resistant Candida albicans Biofilms

Abstract

Candida albicans is the most common fungal pathogen in humans, and most diseases produced by C. albicans are associated with biofilms. Previously, we developed nylon-3 polymers with potent activity against planktonic C. albicans and excellent C. albicans vs. mammalian cell selectivity. Here, we show that these nylon-3 polymers have strong and selective activity against drug-resistant C. albicans in biofilms, as manifested by inhibition of biofilm formation and by killing of C. albicans in mature biofilms. The best nylon-3 polymer (poly-βNM) is superior to the antifungal drug fluconazole for all three strains examined. This polymer is slightly less effective than amphotericin B (AmpB) for two strains, but the polymer is superior against an AmpB-resistant strain.

Antimicrobial cationic polymers: from structural design to functional control

“…[65][66][67][68] By varying the specific structures of cationic groups and hydrophobic groups, the antimicrobial activity against particular microbes can be selectively enhanced as well. [69][70][71][72][73][74][75][76][77] It should be noted that the physical chemistry behind the globally amphiphilic antimicrobial cationic polymers needs to be studied furthermore for providing the guidelines for fabrication of antimicrobial materials with tailor-made structures and functions.…”

Amide side chain amphiphilic polymers disrupt surface established bacterial bio-films and protect mice from chronic Acinetobacter baumannii infection

“…Hedrick and co-workers demonstrated antimicrobial polymeric hydrogels that can disrupt bacterial and fungal biofilms [37]. Gellman and his group showed that nylon-3 polymers can inhibit and disrupt fungal biofilms [38].…”

Antimicrobial Polymers: Mimicking Amino Acid Functionali ty, Sequence Control and Three-dimensional Structure of Host-defen se Peptides

“…Applying these NM subunit homopolymers to biofilms of C. albicans proved their ability to inhibit fungal biofilm growth down to SMIC 80 (concentration to inhibit 80% of biofilm formation) values of 9.4 µg/mL, whilst displaying very little RBC lysis, even at 2000 µg/mL. 65 When NM subunits were supplemented with hydrophobic groups (CP, CH and CO), antifungal activity was diminished, although the more hydrophobic subunits displayed less dramatic decreases in activity relative to CP, attributed to their antifungal effects. Interestingly the DM subunit has some intrinsic antifungal behaviour, but also intrinsic hemolytic effects, whereby upon replacement of the DM unit with hydrophobic groups, HC 10 values increase.…”