DNA & phage defense systems of Vibrio cholerae

Cholera remains a persistent and devastating infectious disease in developing nations, causing millions of cases and thousands of deaths annually, as per World Health Organization (WHO) estimates. Its transmission through water, coupled with Vibrio cholerae's ability to survive independently in the environment, exacerbates the challenge of clean drinking water access, a global health concern unlikely to be resolved soon. Climate change and rising sea temperatures further fuel cholera outbreaks.Our mission is to bridge knowledge gaps in understanding the emergence of pandemic-capable V. cholerae strains, focusing on the 7PET clade responsible for the ongoing seventh cholera pandemic. Recent research, including our own, has unveiled novel immune or defense systems in V. cholerae that combat mobile genetic elements. While most studies have concentrated on these systems' phage defense abilities, our work also explores their impact on plasmid carriage by the bacterium. Our future endeavors aim to comprehensively characterize these newfound defense systems and connect their functions to the biology of 7PET V. cholerae.Specifically, we will investigate the defense systems' target preferences and the regulatory networks governing them. We will also delve into the properties of a recently discovered conjugative plasmid that can counteract plasmid-targeting defense mechanisms. Additionally, we will explore phage predation on V. cholerae and uncover novel defense systems that could serve as a pan-immunity reservoir for 7PET strains. Our study is structured around three key objectives:Aim 1: Comprehensive characterization of defense systems in 7PET V. cholerae.Aim 2: Unraveling a plasmid-mediated countermeasure against defense systems.Aim 3: Discovery of novel defense systems contributing to pan-immunity in the species.This research promises fresh insights into the intricate dynamics between mobile genetic elements, particularly in the spread of conjugative plasmids and the strategies employed by defense systems to thwart these genetic invaders. Furthermore, our in-depth examination of recently identified phage defense systems holds significant implications for potential phage therapy in cholera-endemic regions worldwide.