Sphingolipid diversity in Candida auris: unraveling interclade and drug resistance fingerprints.

In this study, we explored the sphingolipid (SL) landscape in Candida auris, which plays pivotal roles in fungal biology and drug susceptibility. The composition of SLs exhibited substantial variations at both the SL class and molecular species levels among clade isolates. Utilizing principal component analysis, we successfully differentiated the five clades based on their SL class composition. While phytoceramide (PCer) was uniformly the most abundant SL class in all the isolates, other classes showed significant variations. These variations were not limited to SL class level only as the proportion of different molecular species containing variable number of carbons in fatty acid chains also differed between the isolates. Also a comparative analysis revealed abundance of ceramides and glucosylceramides in fluconazole susceptible isolates. Furthermore, by comparing drug-resistant and susceptible isolates within clade IV, we uncovered significant intraclade differences in key SL classes such as high PCer and low long chain base (LCB) content in resistant strains, underscoring the impact of SL heterogeneity on drug resistance development in C. auris. These findings shed light on the multifaceted interplay between genomic diversity, SLs, and drug resistance in this emerging fungal pathogen.

Impact of sphingolipid synthesis inhibition on the drug susceptibility patterns of Trichophyton species.

The well known dermatophyte infections caused by Trichophyton species are an ambiguous problem to treat using the present arsenal of antifungals. This study expounds on the effect of inhibition of sphingolipid pathway on Trichophyton growth. Findings from the drug susceptibility assays suggest sphingolipid inhibition severely restricts the growth of T. interdigitale and T. tonsurans. The observed synergistic effects of combinations of sphingolipid inhibitor and conventional drugs provide a promising treatment strategy against Trichophyton infection.

Beyond membrane components: uncovering the intriguing world of fungal sphingolipid synthesis and regulation.

Sphingolipids (SLs) are essential to fungal survival and represent a major class of structural and signaling lipids. Unique SL structures and their biosynthetic enzymes in filamentous fungi make them an ideal drug target. Several studies have contributed towards the functional characterization of specific SL metabolism genes, which have been complemented by advanced lipidomics methods which allow accurate identification and quantification of lipid structures and pathway mapping. These studies have provided a better understanding of SL biosynthesis, degradation and regulation networks in filamentous fungi, which are discussed and elaborated here.