A peptidoglycan storm caused by β-lactam antibiotic’s action on host microbiota drives Candida albicans infection

Chew Teng Tan, Xiaoli Xu, Yuan Qiao () and Yue Wang ()
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Chew Teng Tan: Agency for Science, Technology and Research
Xiaoli Xu: Agency for Science, Technology and Research
Yuan Qiao: Agency for Science, Technology and Research
Yue Wang: Agency for Science, Technology and Research

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract The commensal fungus Candida albicans often causes life-threatening infections in patients who are immunocompromised with high mortality. A prominent but poorly understood risk factor for the C. albicans commensal‒pathogen transition is the use of broad-spectrum antibiotics. Here, we report that β-lactam antibiotics cause bacteria to release significant quantities of peptidoglycan fragments that potently induce the invasive hyphal growth of C. albicans. We identify several active peptidoglycan subunits, including tracheal cytotoxin, a molecule produced by many Gram-negative bacteria, and fragments purified from the cell wall of Gram-positive Staphylococcus aureus. Feeding mice with β-lactam antibiotics causes a peptidoglycan storm that transforms the gut from a niche usually restraining C. albicans in the commensal state to promoting invasive growth, leading to systemic dissemination. Our findings reveal a mechanism underlying a significant risk factor for C. albicans infection, which could inform clinicians regarding future antibiotic selection to minimize this deadly disease incidence.

Date: 2021
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DOI: 10.1038/s41467-021-22845-2

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