# Synthetic Lethal Therapy Based on Dimorphism for Systemic Infection of Drug‐Resistant Candida albicans

## TL;DR

A new drug combination targeting both forms of Candida albicans improves survival in mice with drug-resistant fungal infections.

## Contribution

A synthetic lethal therapy combining rapamycin and deferasirox, delivered via macrophage membranes, is developed for drug-resistant Candida albicans.

## Key findings

- Rapamycin and deferasirox together prevent morphological transformation in Candida albicans.
- Macrophage membranes enhance drug delivery and reduce side effects in treating systemic infections.
- The therapy significantly improves survival rates in mice with drug-resistant Candida infections.

## Abstract

Systemic infections of Candida albicans are dire, with a mortality rate reaching 60%. The transformation between the yeast and hyphae states of C. albicans resists existing medications and the body's immune defenses. Some currently available drugs only inhibit the growth of the yeast‐form of C. albicans. Therefore, a synthetic lethal therapy that leverages the dimorphism of C. albicans is developed. This therapy utilizes rapamycin to eliminate yeast‐like C. albicans through the mammalian target of rapamycin pathway. Simultaneously, deferasirox restricts iron resources, thereby inhibiting polarization and hyphae formation. As a result, C. albicans cannot evade the lethal effects of drugs and immune cells by undergoing morphological transformations. Furthermore, inspired by the recognition process of fungi by macrophages, macrophage membranes with high expression of dectin‐1 are utilized to deliver rapamycin and deferasirox. The synthetic lethal therapy based on dimorphism significantly improves the survival rate of mice with systemic infections, thereby offering a promising strategy for treating drug‐resistant C. albicans infections.

To tackle the alarming mortality rate linked to Candida albicans infections, a synthetic lethal strategy precisely aimed at the two distinct forms of this fungus: yeast and hyphae is formulated. Ultimately, through the innovative use of macrophage membranes for drug delivery, the effectiveness of this strategy is substantially boosted while simultaneously reducing the immunological side effects associated with the medication.