A broad-spectrum anti-fungal effector dictates bacterial-fungal interkingdom interactions

Area of Science:

• Microbiology
• Molecular Biology
• Pathogenesis

Background:

• Bacteria-fungi interactions are vital in ecosystems and host-associated environments.
• Antagonism via secreted molecules is known, but direct effector delivery into fungal nuclei is poorly understood.
• The type VI secretion system (T6SS) is a key bacterial weapon system.

Purpose of the Study:

• To identify and characterize novel bacterial effectors involved in interkingdom antagonism.
• To elucidate the mechanism of action and delivery of a new anti-fungal effector.
• To explore the therapeutic potential of this effector against fungal pathogens.

Main Methods:

• Identification and characterization of the TseN effector from Acidovorax citrulli.
• Structural and biochemical analyses of TseN and its immunity protein TsiN.
• Transcriptome profiling of co-cultured bacterial-fungal cells.
• In vivo experiments using a murine skin model.

Main Results:

• A novel anti-fungal nuclease effector, TseN, delivered by T6SS, was identified.
• TseN targets the fungal nucleus, inhibiting diverse fungal species including Candida auris.
• T6SS attack induces fungal cell reprogramming, affecting DNA repair and drug resistance.
• TseN demonstrated efficacy in reducing fungal burden in vivo and enhancing azole drug effectiveness.

Conclusions:

• TseN represents a new class of bacterial effectors with broad-spectrum anti-fungal activity.
• The T6SS-mediated delivery of TseN provides a novel mechanism for bacterial antagonism of fungi.
• TseN and its homologs hold promise for developing new anti-fungal therapies and strategies to overcome drug resistance.