Type VI secretion system mutations reduced competitive fitness of classical Vibrio cholerae biotype

Benjamin Kostiuk,Laura Diaz-Satizabal,Francis J Santoriello,Kyung-Jo Lee,Daniel Unterweger,Fabiana Bisaro,Anna N Dhody,Daniele Provenzano,Stefan Pukatzki

doi:10.1038/s41467-021-26847-y

Abstract

The gram-negative bacterium Vibrio cholerae is the causative agent of the diarrhoeal disease cholera and is responsible for seven recorded pandemics. Several factors are postulated to have led to the decline of 6th pandemic classical strains and the rise of El Tor biotype V. cholerae, establishing the current 7th pandemic. We investigated the ability of classical V. cholerae of the 2nd and 6th pandemics to engage their type six secretion system (T6SS) in microbial competition against non-pandemic and 7th pandemic strains. We report that classical V. cholerae underwent sequential mutations in T6SS genetic determinants that initially exposed 2nd pandemic strains to microbial attack by non-pandemic strains and subsequently caused 6th pandemic strains to become vulnerable to El Tor biotype V. cholerae intraspecific competition. The chronology of these T6SS-debilitating mutations agrees with the decline of 6th pandemic classical strains and the emergence of 7th pandemic El Tor V. cholerae.

Highlights

The gram-negative bacterium Vibrio cholerae is the causative agent of the diarrhoeal disease cholera and is responsible for seven recorded pandemics
Compatibility groups were further classified into subfamilies to account for distinct TsiV1 amino acid sequences among the same modules: the 6th pandemic classical strains are represented by compatibility groups A1A1A1, A2A1A1 and A3A1A1 (MZO-2); A4A1A1 was identified in this study
We examined three aspects of competitiveness across pandemic cholera strains: the ability to engage in T6SS battle with commensal bacteria, compete with nonpandemic strains and compete with other pandemic strains

Summary

Introduction

The gram-negative bacterium Vibrio cholerae is the causative agent of the diarrhoeal disease cholera and is responsible for seven recorded pandemics. Several factors are postulated to have led to the decline of 6th pandemic classical strains and the rise of El Tor biotype V. cholerae, establishing the current 7th pandemic. We report that classical V. cholerae underwent sequential mutations in T6SS genetic determinants that initially exposed 2nd pandemic strains to microbial attack by non-pandemic strains and subsequently caused 6th pandemic strains to become vulnerable to El Tor biotype V. cholerae intraspecific competition. Contraction of the T6SS outer sheath ejects an inner tube consisting of polymerised Hcp proteins, capped with effector proteins, into adjacent bacteria These effectors are toxic unless inhibited by cognate immunity proteins in the attacked bacterium. El Tor and classical strains regulate ~1 in 8 genes differently, resulting in biotype-specific spatial-temporal expression of the main virulence factors, cholera toxin (CT) and toxin-coregulated pilus (TCP)[9,10]. Numerous additional virulence factors encoded within El Tor genomes are either absent or differentially regulated in classical

Methods

Findings

Conclusion