Derivates of the Antifungal Peptide Cm-p5 Inhibit Development of Candida auris Biofilms In Vitro

Abstract

Growth in biofilms as a fascinating and complex microbial lifestyle has become widely accepted as one of the key features of pathogenic microbes, to successfully express their full virulence potential and environmental persistence. This also increases the threat posed by Candida auris, which has a high intrinsic ability to persist on abiotic surfaces including those of surgical instruments and medical tubing. In a previous study, cyclic and helical-stabilized analogues of the antifungal peptide Cm-p5 were designed and synthetized, and proved to have increased activities against C. albicans and C. parapsilosis, but not against planktonic C. auris cells cultivated in suspension cultures. Here, we demonstrate, initially, that these derivatives, however, exhibited semi-inhibitory concentrations between 10–21 µg/mL toward C. auris biofilms. Maturated biofilms were also arrested between 71–97%. These novel biofilm inhibitors may open urgently needed new routes for the development of novel drugs and treatments for the next stage of fight against C. auris.

Antimicrobial Peptides Pom-1 and Pom-2 from Pomacea poeyana Are Active against Candidaauris, C. parapsilosis and C. albicans Biofilms

“…Interestingly, in contrary, in the viability assay Pom-1 performed best against C. auris planktonic cells. This finding is a remarkable parallel to derivatives of a peptide from the coastal mollusk Cenchritis muricatus which also failed as antimicrobial peptides against C. auris planktonic cells but efficiently could inhibit biofilm formation [ 37 ]. Nevertheless, the respective semi-inhibitory concentration for biofilm inhibition (IC 50 Biofilm ) of Pom-1 were 4.2 µg/mL for C. auris , 4.6 µg/mL for C. albicans and 3.1 µg/mL for C. parapsilosis ( Figure 3 a).…”

“…Only moderate activities against planktonic cells has also been described for a set of derivatives a snail derived natural antimicrobial peptide, which turned out to possess remarkable capabilities to inhibit the biofilm formation of C. auris probably based on a yet so far uncharacterized additional activity at very low concentrations of the peptides [ 37 ].…”

The Neosartorya fischeri Antifungal Protein 2 (NFAP2): A New Potential Weapon against Multidrug-Resistant Candida auris Biofilms

“…Kubiczek et al (2020) reported that antifungal peptides might have a promising anti-biofilm activity: derivates of the antifungal peptide Cm-p5 exhibited a semi-inhibitory effect at concentrations ranging from 10 to 21 mg/L against C. auris biofilms. In addition, the mature sessile populations were also inhibited by 71–97% [ 33 ].…”

Aprepitant, an antiemetic agent, interferes with metal ion homeostasis ofCandida aurisand displays potent synergistic interactions with azole drugs

“…To assess the activity of aprepitant/itraconazole against mature biofilms, C. auris cells (at ~1 × 10 5 CFU/ml) were seeded in tissue culture-treated 96-well plates and incubated for 24 h at 35°C to allow for the formation of mature biofilms [ 31–33 ]. Fresh RPMI 1640 media supplemented with aprepitant, itraconazole, or aprepitant/itraconazole, at the same concentrations indicated above, were added to the formed biofilms and incubated for another 24 h at 35°C.…”