Echinocandin Resistance in Candida auris Occurs in the Murine Gastrointestinal Tract Due to FKS1 Mutations

Candida auris is resistant to multiple antifungal agents. This study investigated its antifungal susceptibility and explored FKS1 mutations across the isolates from mice enterically colonized with wild-type C. auris and treated with echinocandin. Resistant C. auris with FKS1 mutations, including S639F, S639Y, D642Y, R1354H, or R1354Y, were isolated and found to be micafungin- and caspofungin-resistant in vivo; however, the MICs of isolates with mutation in R1354 remained below the micafungin breakpoint in vitro.

 

Comments：Candida auris is an emerging multidrug-resistant fungal pathogen that can cause invasive infections associated with high mortality rates. In this study, researchers investigated the antifungal susceptibility of C. auris and explored the mutations in the FKS1 gene across isolates from mice that were colonized with wild-type C. auris and treated with echinocandin, a class of antifungal agents.

The study found that some C. auris isolates were resistant to micafungin and caspofungin, two echinocandin drugs commonly used to treat fungal infections. The resistant isolates were found to have mutations in the FKS1 gene, specifically in the amino acid positions S639F, S639Y, D642Y, R1354H, or R1354Y.

Interestingly, the study found that the MICs (minimum inhibitory concentrations) of isolates with mutations in R1354 remained below the micafungin breakpoint in vitro, which means that these isolates were not classified as resistant to micafungin based on standard laboratory testing. However, these isolates were still found to be micafungin-resistant in vivo, meaning that they were able to survive and proliferate in the presence of the drug in a living host.

Overall, these findings highlight the importance of monitoring antifungal resistance in C. auris and the potential limitations of standard laboratory testing methods. The emergence of multidrug-resistant strains of C. auris underscores the need for continued research and development of new antifungal agents to combat this emerging public health threat.

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S3073	Caspofungin (MK-0991) Acetate	Caspofungin Acetate (MK-0991, L-743872) is an lipopeptide antifungal β-1,3-glucan synthase inhibitor.

Related Targets

Fungal