Between Feast and Famine: Exploring Vibrio cholerae Adaptive Strategies in Nutrient-Limited Aquatic Environments

Abstract

Vibrio cholerae, the causative agent of cholera, exemplifies the remarkable adaptability of bacterial pathogens. The bacterium’s ability to seamlessly transition between aquatic reservoirs and human hosts in a complex ecological cycle is what allows environmental persistence, sustaining endemic cholera worldwide. Whilst deeply dormant forms such as the Viable but non-culturable (VBNC) and Conditionally Viable Environmental Cells (CVECs) have been characterized - the critical early adaptation phase, when freshly shed cells first encounter nutrient-limited aquatic reservoirs, remains incompletely investigated. This knowledge gap limits the ability to predict outbreak risk from environmental reservoirs and develop targeted surveillance strategies. This thesis developed a laboratory model of early V. cholerae environmental adaptation using artificial seawater (5% Instant Ocean, 1.5 ppt salinity) that mimics epidemiologically relevant estuarine conditions. Time-course analysis revealed that V. cholerae C6706 cells lose culturability within 4-6 days while undergoing coordinated physiological and metabolic changes including dramatic ATP depletion (>10,000-fold decrease within 24 hours), progressive morphological transformation from vibrioid to coccoid forms (14% to 60% coccoid over 7 days), and formation of multicellular aggregates with extracellular matrix components. Most interestingly, RT-qPCR analysis using a novel Relative Decay Index metric revealed that virulence genes (ctxA, tcpA) are downregulated less dramatically than housekeeping genes (gyrA) during environmental stress, indicating selective preservation of pathogenic capacity despite severe metabolic shutdown. This differential regulation raises the possibility of selective virulence gene preservation during environmental stress. These findings provide a detailed characterization of early environmental adaptation, documenting coordinated changes in metabolism, morphology, and gene expression.