K21 Compound, a Potent Antifungal Agent: Implications for the Treatment of Fluconazole-Resistant HIV-Associated Candida Species

Abstract

Background/Objectives: With mucocutaneous candidiasis being highly prevalent in HIV patients, the emergence of fluconazole-resistant Candida species forms a major challenge in treating and eradicating these infections. The objective of this study was to establish the antifungal activity of K21, a membrane-rupturing antimicrobial compound derived from a silica quaternary ammonium compound (SiQAC) with tetraethoxysilane (TEOS). Methods: The study sample included 81 Candida species of which 9 were type strains and 72 were clinical isolates. Minimum inhibitory concentrations, synergy, fractional inhibitory concentration index (FICI), and time kill assays were determined by broth microdilution. Electron microscopy (EM) was used to determine the qualitative changes brought about after treatment with K21. Results: K21 inhibited the growth of all fluconazole-resistant and susceptible Candida strains with only 2 h of exposure required to effectively kill 99.9% of the inoculum, and a definite synergistic effect was observed with a combination of K21 and fluconazole. EM demonstrated the presence of two forms of extracellular vesicles indicative of biofilm formation and cell lysis. Conclusion: The study established the efficacy of K21 as an antifungal agent and with fluconazole-resistant candidiasis on the increase, the development of K21 can provide a promising alternative to combat acquired drug resistance.

Autophagy of Candida albicans cells after the action of earthworm Venetin-1 nanoparticle with protease inhibitor activity

“…After the action of Venetin-1, numerous post-division scars on the surface of cells were observed. They were similar to those observed in SEM micrographs after exposure to fluconazole, a known drug that disrupts the structure of the cell membrane of C. albicans 79 . In our opinion, the cell dividing many times in a short time does not keep up with the production of building compounds required to synthesize the structures of the cell wall in place of scars.…”

Antifungal Activity of Linear and Disulfide-Cyclized Ultrashort Cationic Lipopeptides Alone and in Combination with Fluconazole against Vulvovaginal Candida spp.

“…It seems to be an effective alternative to fluconazole against Candida strains resistant to this mycostatic. K21 also shows synergism with triazoles towards NCAC, including C. dubliniensis and C. tropicalis, but no such effect was observed for C. albicans [66]. Meanwhile, a combination of another quaternary ammonium compound, domiphen bromide, with miconazole (imidazole) showed a synergistic effect against not only Candida planktonic cells, but also a biofilm, although this effect did not occur in the case of triazoles, including fluconazole [67].…”

Incorporation of Inclusion Complexes in the Dissolvable Microneedle Ocular Patch System for the Efficiency of Fluconazole in the Therapy of Fungal Keratitis

“…First, 5 mL of each fungal suspension (5 × 10 5 cfu/mL) was added into 30 mL of RPMI-1640 broth medium containing samples with MIC, 2 × MIC, and 4 × MIC and then incubated using an orbital shaker at 37 °C for 24 h. Next, the aliquots were taken (100 μL) at predetermined time points of 0, 2, 4, 6, 8, 12, 18, and 24 h, diluted with broth medium RPMI-1640, then inoculated into sterile SDA media, and incubated at 37 °C for 24 h. Finally, the number of colony growth was observed. The average number of colonies (log cfu/mL) versus time (h) was constructed. , Parameters of fungicide activity were characterized by a decrease in microbial growth of ≥3 logs cfu/mL or a 99.99% reduction in microbial growth against the initial inoculum after 24 h. Conversely, fungistatic activity was characterized by a decrease in microbial growth <3 logs cfu/mL or a decrease in microbial growth of less than 99.99% after 24 h …”

“…The average number of colonies (log cfu/mL) versus time (h) was constructed. 36,37 Parameters of fungicide activity were characterized by a decrease in microbial growth of ≥3 logs cfu/mL or a 99.99% reduction in microbial growth against the initial inoculum after 24 h. Conversely, fungistatic activity was characterized by a decrease in microbial growth <3 logs cfu/mL or a decrease in microbial growth of less than 99.99% after 24 h. 38 2.9. Preparation of DMN.…”