期刊
NATURE COMMUNICATIONS
卷 12, 期 1, 页码 -出版社
NATURE PORTFOLIO
DOI: 10.1038/s41467-021-22845-2
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资金
- National Medical Research Council [NMRC/OFIRG0025/2016, OFIRG/0072/2018]
Broad-spectrum antibiotics can induce the release of peptidoglycan fragments by commensal bacteria, leading to the invasive growth of C. albicans and systemic dissemination, which is a significant risk factor for infection.
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 commensalpathogen transition is the use of broad-spectrum antibiotics. Here, we report that beta -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 beta -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. A risk factor for invasive Candida albicans infection is the use of broad-spectrum antibiotics, but the reasons are poorly understood. Here, the authors show in mice that beta -lactam antibiotics cause commensal bacteria to release peptidoglycan fragments that induce the invasive hyphal growth of C. albicans, leading to systemic dissemination.
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