Selective Elimination of Vibrio Pathogens via the Synergy of a Type Six Secretion System and a Natural Phenazine Antibiotic

Abstract

Vibrio species are most often studied in the context of human disease; multiple Vibrio species, including Vibrio cholerae, are widespread mammalian pathogens. In this work, we describe the isolation of a vibriocidal strain of Aeromonas dhakensis, named A603. We determine that its vibriocidal activity comes from a synergy between A603’s Type Six Secretion System and a synthesized phenazine antibiotic, AdPhen. Remarkably, non-Vibrio taxa resist this killing. We identify 3 systems in Vibrio strains that confer increased AdPhen resistance. However, A603’s T6SS activity overcomes efflux-mediated AdPhen resistance in newly generated V. cholerae mutants, likely through membrane potential dissipation and disruption of essential cation gradients. A603 uses both AdPhen and its T6SS to protect the host from invading Vibrio pathogens, like AHPND strains of V. parahaemolyticus. A603 guards aquatic hosts from AHPND-related microbiome disruptions without significant host colonization or changes to native flora. A603’s easy application, low colonization of hosts, and minimal alteration of microbiome composition or function makes it a promising new probiotic for prevention of vibriosis in aquatic hosts. While A603 itself cannot colonize mammalian hosts, the lessons learned from its activity can be leveraged to improve prophylaxis and treatment of Vibrio diseases, including cholera.