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

Area of Science:

• Medical Mycology
• Microbiology
• Immunology

Background:

• * *Candida albicans* is a fungus that can cause severe infections in immunocompromised individuals.
• * Broad-spectrum antibiotic use is a known risk factor for *C. albicans* infections, but the mechanism is unclear.

Purpose of the Study:

• * To investigate how broad-spectrum antibiotics contribute to *Candida albicans* infections.
• * To identify the microbial factors responsible for the transition of *C. albicans* from commensal to pathogenic.

Main Methods:

• * Analysis of peptidoglycan fragments released by bacteria treated with beta-lactam antibiotics.
• * Identification of active peptidoglycan subunits that induce hyphal growth in *C. albicans*.
• * In vivo studies using mouse models to assess the impact of antibiotic treatment on gut microbiota and *C. albicans* dissemination.

Main Results:

• * Beta-lactam antibiotics induce bacteria to release substantial amounts of peptidoglycan fragments.
• * Specific peptidoglycan subunits, including tracheal cytotoxin and fragments from *Staphylococcus aureus*, stimulate invasive hyphal growth in *C. albicans*.
• * Antibiotic-induced peptidoglycan release creates a
• peptidoglycan storm
• in the gut, promoting *C. albicans* invasive growth and systemic spread.

Conclusions:

• * Bacterial peptidoglycan fragments released during antibiotic treatment are key drivers of *Candida albicans* pathogenesis.
• * Understanding this mechanism can guide antibiotic selection to mitigate the risk of invasive fungal infections.
• * This research reveals a critical link between antibiotic use, bacterial products, and opportunistic fungal infections.