Vibrio cholerae motility exerts drag force to impede attack by the bacterial predator Bdellovibrio bacteriovorus

Miles C Duncan,Daniel E Kadouri,John C Forbes,Lauren M Shull,Robert M Q Shanks,Afsar Ali,Andrew Camilli,Y Nguyen,David W Lazinski,Rebecca K Gillette

doi:10.1038/s41467-018-07245-3

Abstract

The bacterial predator Bdellovibrio bacteriovorus is evolved to attack and kill other bacteria, including the human intestinal pathogen Vibrio cholerae. Although B. bacteriovorus exhibit a broad prey range, little is known about the genetic determinants of prey resistance and sensitivity. Here we perform a genetic screen on V. cholerae and identify five pathways contributing to predation susceptibility. We find that the essential virulence regulators ToxR/S increase susceptibility to predation, as mutants of these genes are more resistant to predation. We observe by flow cytometry that lipopolysaccharide is a critical defense, as mutants lacking O-antigen are rapidly attacked by predatory B. bacteriovorus. Using polymer solutions to alter media viscosity, we find that when B. bacteriovorus attacks motile V. cholerae, increased drag forces slow its ability to prey. These results provide insights into key prey resistance mechanisms, and may be useful in the application of B. bacteriovorus in treating infections.

Highlights

The bacterial predator Bdellovibrio bacteriovorus is evolved to attack and kill other bacteria, including the human intestinal pathogen Vibrio cholerae
To identify prey pathways playing a role in predation, we created mTn10 transposon libraries in V. cholerae and E. coli (Supplementary Data 1) and subjected them to predation by B. bacteriovorus
In the intervening years little research has focused on prey genes involved in the predation process, nor has a specific receptor for B. bacteriovorus been identified in any prey species

Summary

Introduction

The bacterial predator Bdellovibrio bacteriovorus is evolved to attack and kill other bacteria, including the human intestinal pathogen Vibrio cholerae. Within 10–20 min of attachment, B. bacteriovorus invades the prey periplasm where it kills the host and remodels host peptidoglycan to create a spherical bdelloplast[4] Inside this protected niche, it degrades the host’s cytosolic proteins and nucleic acids, using these products to fuel its own replication before it lyses its prey and releases several daughter cells[5]. Owing to the alarming rise of antibiotic-resistant bacteria and dearth of new treatments entering the clinic, B. bacteriovorus is being evaluated for therapeutic purposes and has recently been shown to attenuate Klebsiella pneumoniae and Shigella flexneri in vivo[6,7] Another susceptible prey species is Vibrio cholerae[8,9], the causative agent of the severe diarrheal disease cholera. We find that drag exerted by the motion of V. cholerae slows the predator’s ability to kill its prey

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