The ATO gene family governs Candida albicans colonization in the dysbiotic gastrointestinal tract

Summary

This study shows that the fungus Candida albicans uses a family of protein transporters called ATO to absorb acetate, a fatty acid produced by gut bacteria. When mice were treated with antibiotics that killed their beneficial bacteria, C. albicans could colonize their guts better if it had working ATO transporters. The research reveals that fungi have evolved special systems to take advantage of nutrients left behind when the normal gut bacteria are disrupted, which helps explain why fungal infections are more common after antibiotic use.

Background

Candida albicans colonizes the human gut where short-chain fatty acids (SCFAs) serve as carbon sources. C. albicans possesses the largest known microbial ATO (acetate transporter ortholog) gene family, encoding putative SCFA transport proteins whose functional roles in gut colonization remain unclear.

Objective

To investigate the role of the ATO gene family in SCFA utilization and assess its contribution to stable C. albicans colonization of the mammalian gastrointestinal tract under dysbiotic conditions.

Results

ATO1 mediates the majority of acetate uptake in C. albicans, and deletion of all ATO genes abolishes efficient acetate transport. While ATO1 inactivation alone impairs growth on acetate, only complete deletion of the entire ATO gene family significantly reduces stable gut colonization in antibiotic-treated mice. Multiple ATO family members collectively promote fungal fitness during dysbiotic conditions.

Conclusion

The ATO gene family has expanded and diversified during C. albicans evolution to promote fitness during gut colonization through efficient SCFA assimilation, particularly acetate uptake, highlighting the importance of transporter gene expansion in fungal commensalism.
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