Screening of a Candida albicans drug resistance transporter MLT1
EMSL Project ID
50937
Abstract
Fungal infections present a rising and underappreciated threat to health. The CDC identified one species of fungal infections, Candida, as one of 18 leading antibiotic resistant infection threats. Infections often occur in hospital settings and can have extremely high mortality rates of 50% or more. At the root of the epidemic are innate drug and stress tolerance mechanisms that permit Candida to survive drug treatment and one’s own immune system. One such contributing player in therapeutic escape is the drug and lipid transporter MLT1 from Candida albicans, the causative agent of one of the common fungal infections in the US. MLT1 resides in an internal compartment known as the vacuole, which handles nutrient processing and waste handling for the cell. MLT1 plays a dual role by sequestering antifungal drugs and by recycling lipids damaged by drug treatment. Here, we aim to generate preliminary cryo-EM imaging data of MLT1. We have successfully generated pure Candida albicans MLT1 protein expressed in baker’s yeast, and have imaged MLT1 using negative staining techniques. We seek to optimize MLT1 freezing conditions in vitrified ice for further downstream data collections. Ultimately, these structural studies of MLT1 will set the stage for more rational design of antifungals that either 1) do not become transported by MLT1, thereby combating drug resistance or 2) inhibit MLT1 themselves. These could lead to new generations of antifungal drugs that more effectively combat the rising health threat of fungal infections.
Project Details
Start Date
2019-06-15
End Date
2019-10-15
Status
Closed
Released Data Link
Team
Principal Investigator
Team Members