Researchers Discover Antibacterial Proteins with High Species Specificity
Recently, Associate Professor Fu Yang, a tenured associate professor at the School of Medicine, Southern University of Science and Technology, has made progress in the research field of microbial competition mechanisms mediated by type VI secretion system (T6SS) antibacterial effectors (hereinafter referred to as antibacterial proteins), and discovered T6SS antibacterial proteins TseVs with high species specificity. The related results were published as a cover article in Cell Host & Microbe.
Vibrio bacteria are widely present in marine and estuarine delta environments, including a large number of environmental pathogens and highly toxic pathogens, which are closely related to human health and food industry safety. With the increasingly serious problem of antibiotic resistance, effective treatment methods for Vibrio have been continuously reduced, and new antibacterial mechanisms and technical research are urgently needed to solve the problems of resistance and lack of available drugs.
For this reason, the research team took a different approach and studied harmless environmental strains of Vibrio cholerae isolated from the natural ecological domain from the perspective of species competition. They found that some harmless environmental strains have an active T6SS and carry a Vibrio species-specific antibacterial protein TseVs. This protein can be delivered across membranes relying on the bacterial T6SS, producing a significant bactericidal effect when entering sensitive Vibrio cells, and can efficiently eliminate sensitive Vibrio both in the host and in the natural environment.
The TseVs protein forms dimers on the inner and outer membranes of Vibrio bacteria through its transmembrane helix region rich in "glycine zipper" structure and creates transmembrane pores. These pores allow sodium ions to enter and potassium ions to leak out, thereby specifically disrupting the membrane ion homeostasis of sensitive Vibrio, further interfering with the energy supply system and leading to cell death. However, non-Vibrio bacteria can rely on their own membrane potential system to compensate for the ion homeostasis imbalance caused by the TseVs protein pores, thereby protecting themselves without relying on the TseVs-specific immune protein TsiVs.
Bioinformatics analysis shows that the TseVs protein gene is mainly distributed in harmless environmental Vibrio and shows a significant evolutionary expansion trend in ecological samples from many parts of the world, revealing that this protein plays an important role in bacterial population competition.
This study expands the understanding of T6SS-mediated microbial competition mechanisms and provides an ideal paradigm for precision antibacterial strategies. TseVs have multiple advantages such as strong species selectivity, high killing efficiency, low tendency to produce drug resistance, and low possibility of transfer through horizontal gene recombination, and are expected to become engineerable antibacterial modules in synthetic biology. This research provides detailed data for understanding the ecological mechanism of community succession between pathogenic and non-pathogenic Vibrio, and lays a solid theoretical foundation