Transcriptional Response of Candida albicans to Nanostructured Surfaces Provides Insight into Cellular Rupture and Antifungal Drug Sensitization

Abstract

The rise in resistance levels against antifungal drugs has necessitated the development of strategies to combat fungal infections. Nanoscale antimicrobial surfaces, found on the cuticles of insects, have recently emerged as intriguing alternative antifungal strategies that function passively via contact and induced cell rupture. Nanostructured surfaces (NSS) offer a potentially transformative antimicrobial approach to reducing microbial biofilm formation. We examined the transcriptional response of Candida albicans, an opportunistic pathogen that is also a commensal dimorphic fungus, to the NSS found in the wings of Neotibicen spp. cicada and found characteristic changes in the expression of C. albicans genes associated with metabolism, biofilm formation, ergosterol biosynthesis, and DNA damage response after 2 h of exposure to the NSS. Further validation revealed that these transcriptional changes, particularly in the ergosterol biosynthesis pathway, sensitize C. albicans to major classes of antifungal drugs. These findings provide insights into NSS as antimicrobial surfaces and as a means of controlling biofilm formation.

Disclosing the Antifungal Mechanisms of the Cyclam Salt H4[H2(4-CF3PhCH2)2Cyclam]Cl4 against Candida albicans and Candida krusei

“…The significant decrease in intracellular ATP levels caused by compound 1 thus clearly highlights its influence on energy metabolism in C. albicans and C. krusei. Furthermore, ATP is a critical energy source for cellular functions, and a decrease in ATP levels can impair various biological processes necessary for the organism's viability [29].…”

“…Furthermore, C. krusei exhibits differences in cell wall composition/structure compared to C. albicans, which can also influence its response to antifungal compounds like compound 1. In addition, C. krusei is intrinsically resistant to fluconazole, both in vitro and in vivo [29,31,32]. This inherent resistance in C. krusei makes it more challenging to treat compared to other Candida species like C. albicans.…”