A New Front in Microbial Warfare-Delivery of Antifungal Effectors by the Type VI Secretion System.

Katharina Trunk,Janet Quinn,Sarah J Coulthurst

doi:10.3390/jof5020050

Katharina Trunk, Janet Quinn + Show 1 more

Open Access

https://doi.org/10.3390/jof5020050

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Abstract

Microbes typically exist in mixed communities and display complex synergistic and antagonistic interactions. The Type VI secretion system (T6SS) is widespread in Gram-negative bacteria and represents a contractile nano-machine that can fire effector proteins directly into neighbouring cells. The primary role assigned to the T6SS is to function as a potent weapon during inter-bacterial competition, delivering antibacterial effectors into rival bacterial cells. However, it has recently emerged that the T6SS can also be used as a powerful weapon against fungal competitors, and the first fungal-specific T6SS effector proteins, Tfe1 and Tfe2, have been identified. These effectors act via distinct mechanisms against a variety of fungal species to cause cell death. Tfe1 intoxication triggers plasma membrane depolarisation, whilst Tfe2 disrupts nutrient uptake and induces autophagy. Based on the frequent coexistence of bacteria and fungi in microbial communities, we propose that T6SS-dependent antifungal activity is likely to be widespread and elicited by a suite of antifungal effectors. Supporting this hypothesis, homologues of Tfe1 and Tfe2 are found in other bacterial species, and a number of T6SS-elaborating species have been demonstrated to interact with fungi. Thus, we envisage that antifungal T6SS will shape many polymicrobial communities, including the human microbiota and disease-causing infections.

Highlights

IntroductionBacteria and fungi are ubiquitous in nature and co-colonise numerous environmental niches
Bacteria and fungi are ubiquitous in nature and co-colonise numerous environmental niches.Focussing on the human host, such cross-kingdom interactions are prevalent within the human microbiota, and are commonly associated with biofilms and medically relevant infections [1]
We present evidence that T6SS-dependent antifungal activity is likely to be a widespread determinant of microbial community composition, before finishing with the key questions and opportunities for future research afforded by this exciting new area of biology

Summary

Introduction

Bacteria and fungi are ubiquitous in nature and co-colonise numerous environmental niches. Focussing on the human host, such cross-kingdom interactions are prevalent within the human microbiota, and are commonly associated with biofilms and medically relevant infections [1]. Such interactions may be chemical, physical or occur through alteration of the shared environmental niche, and, importantly, can be synergistic or antagonistic for the species involved. P. aeruginosa preferentially binds to and forms biofilms on hyphal C. albicans cells and kills the fungus through the action of two virulence factors, secreted phospholipase C and redox-active phenazines [8]. We present evidence that T6SS-dependent antifungal activity is likely to be a widespread determinant of microbial community composition, before finishing with the key questions and opportunities for future research afforded by this exciting new area of biology

Occurrence of Type VI Secretion Systems

Effector Delivery by the Type VI Secretion System

Identification of T6SS Antifungal Effectors

Mode of Action of Tfe1 and Tfe2

Prevalence of T6SS-Dependent Antifungal Activity

Outstanding Questions