Hierarchical, non-additive MARTX effector interplay rewires host transcription to drive Vibrio vulnificus invasion and lethal sepsis

Here, we systematically dissect effector interplay in the highly virulent pathogen Vibrio vulnificus. In the M-type MARTX toxin strain MO6-24/O, which delivers four effectors, we generated catalytically-inactivating point mutations in all combinations in situ.

We found that effector composition influences virulence potential, revealing both virulence and anti-virulence factors. Integrated transcriptomics revealed that coordinated effector activity governs the magnitude and coherence of host response. Two functional effector modules define a regulatory–metabolic axis and a silencing–execution axis, each partially contributing to virulence.