Bacterial pathogens deliver water/solute-permeable channels as a virulence strategy

bioRxiv [Preprint]. 2023 Jul 29:2023.07.29.547699. doi: 10.1101/2023.07.29.547699.


Many animal and plant pathogenic bacteria utilize a type III secretion system to deliver effector proteins into the host cell 1,2 . Elucidation of how these effector proteins function in the host cell is critical for understanding infectious diseases in animals and plants 3-5 . The widely conserved AvrE/DspE-family effectors play a central role in the pathogenesis of diverse phytopathogenic bacteria 6 . These conserved effectors are involved in the induction of "water-soaking" and host cell death that are conducive to bacterial multiplication in infected tissues. However, the exact biochemical functions of AvrE/DspE-family effectors have been recalcitrant to mechanistic understanding for three decades. Here we show that AvrE/DspE-family effectors fold into a β-barrel structure that resembles bacterial porins. Expression of AvrE and DspE in Xenopus oocytes results in (i) inward and outward currents, (ii) permeability to water and (iii) osmolarity-dependent oocyte swelling and bursting. Liposome reconstitution confirmed that the DspE channel alone is sufficient to allow the passage of small molecules such as fluorescein dye. Targeted screening of chemical blockers based on the predicted pore size (15-20 Å) of the DspE channel identified polyamidoamine (PAMAM) dendrimers as inhibitors of the DspE/AvrE channels. Remarkably, PAMAMs broadly inhibit AvrE/DspE virulence activities in Xenopus oocytes and during Erwinia amylovora and Pseudomonas syringae infections. Thus, we have unraveled the enigmatic function of a centrally important family of bacterial effectors with significant conceptual and practical implications in the study of bacterial pathogenesis.

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