Selective Antifungal Activity and Fungal Biofilm Inhibition of Tryptophan Center Symmetrical Short Peptide

Abstract

Candida albicans, an opportunistic fungus, causes dental caries and contributes to mucosal bacterial dysbiosis leading to a second infection. Furthermore, C. albicans forms biofilms that are resistant to medicinal treatment. To make matters worse, antifungal resistance has spread (albeit slowly) in this species. Thus, it has been imperative to develop novel, antifungal drug compounds. Herein, a peptide was engineered with the sequence of RRFSFWFSFRR-NH2; this was named P19. This novel peptide has been observed to exert disruptive effects on fungal cell membrane physiology. Our results showed that P19 displayed high binding affinity to lipopolysaccharides (LPS), lipoteichoic acids (LTA) and the plasma membrane phosphatidylinositol (PI), phosphatidylserine (PS), cardiolipin, and phosphatidylglycerol (PG), further indicating that the molecular mechanism of P19 was not associated with the receptor recognition, but rather related to competitive interaction with the plasma membrane. In addition, compared with fluconazole and amphotericin B, P19 has been shown to have a lower potential for resistance selection than established antifungal agents.

Designing double-site lipidated peptide amphiphiles as potent antimicrobial biomaterials to combat multidrug-resistant bacteria

“…As shown in Figure 3D, the bactericidal action of WL-C 6 was rapid, and is similar to that observed for many AMPs, indicating that WL-C 6 may adopt a similar membrane-disruptive mechanism of action (Song et al, 2019;Chou et al, 2021;Wang et al, 2022). Therefore, in order to gain a preliminary understanding of the WL-C 6 action site, we conducted super-resolution fluorescence imaging using 3D structured illumination microscopy (3D-SIM) to monitor the localization site of WL-C 6 in E. coli.…”

“…AMPs are small molecular active peptides and have been widely isolated and characterized from animals, plants, bacteria, fungi, protists, and archaea (Wang et al, 2016). Different AMPs show different biological functions, such as antibacterial (Shao et al, 2021;Panteleev et al, 2022;Wang et al, 2022), antibiofilm (Zai et al, 2021), antivirals (Ji et al, 2018), antifungal (Chou et al, 2021), anticancer and immunomodulatory (Lugo et al, 2019;Mookherjee et al, 2020). More than 22,400 AMPs have been isolated from nature or created synthetically in the lab as of this writing (Shi et al, 2022).…”

A Cecropin-4 Derived Peptide C18 Inhibits Candida albicans by Disturbing Mitochondrial Function

“…Most of the AMPs adopt an amphipathic α-helical structure and have a membrane mimetic mechanism of action. For example, P19, a central-symmetric α-helix structural peptide, displayed disruptive effects on fungal cell membrane physiology by competitive interaction with the plasma membrane (Chou et al, 2021). Another Dual-Targeted α-helical peptide exerted antifungal effects due to membrane disruption and induction of reactive oxygen species (ROS) production (Yang et al, 2020).…”

Peptide Designs for Use in Caries Management: A Systematic Review

“…Erythrocytes and human gingival fibroblasts were the most used cell lines in the studies’ biocompatibility testing. However, some studies still used non-human cells [ 84 ] or non-oral cells [ 79 ]. Furthermore, the main limitation of all these studies in terms of their assessment of novel peptides was that many of them did not assess the stability of the peptides in human saliva.…”