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A widely-occurring family of pore-forming effectors broadens the impact of the Serratia Type VI secretion system

ABSTRACT: The ability to compete with diverse competitors is essential for bacteria to succeed in microbial communities. A widespread strategy for inter-bacterial competition is the delivery of antibacterial toxins, or effector proteins, directly into rival cells using the Type VI secretion system (T6SS). Whilst a large number of broad-spectrum enzymatic T6SS effectors have been described, relatively few which form pores in target cell membranes have been reported. Here, we describe a widely-occurring new family of T6SS-dependent pore-forming effectors, exemplified by Ssp4 of Serratia marcescens Db10. We show that Ssp4 forms cation-selective pores in vitro and use molecular dynamics simulations to support a high resolution structural model of a tetrameric membrane pore formed by Ssp4. Notably, the ion selectivity of Ssp4, its distribution and its impact on intoxicated cells is distinct from that of Ssp6, the other cation-selective pore-forming toxin delivered by the same T6SS. We further discovered that Ssp4 is active against a wider range of target species than Ssp6, highlighting that T6SS effectors are not always broad-spectrum. Finally, use of Tn-seq to identify Ssp4-resistant mutants revealed that a mucA mutant of Pseudomonas fluorescens, which overproduces extracellular polysaccharide, provides resistance to T6SS attacks. We conclude that possession of two distinct T6SS-dependent pore-forming toxins may be a common strategy to ensure effective de-energisation of closely- and distantly-related competitors.

ORGANISM(S): Pseudomonas simiae

PROVIDER: GSE301252 | GEO | 2025/10/31

REPOSITORIES: GEO

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