Taming Vibrio cholerae with cationic polymers: engineering bacterial physiology by interfering with communication and virulence

Pérez-Soto, Nicolás (2018). Taming Vibrio cholerae with cationic polymers: engineering bacterial physiology by interfering with communication and virulence. University of Birmingham. Ph.D.

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Abstract

The Gram-negative Vibrio cholerae is native to aquatic environments and an important human pathogen causing cholera disease. The induction of virulence in this bacterium is subjected to a wide variety of stimuli including environmental cues and quorum sensing. In this study, non-bactericidal cationic polymers were designed to capture Vibrio cholerae into clusters resulting in physiological changes. Poly(N-(3-aminopropyl) methacrylamide) (P1), poly(N-[3-dimethylamino)propyl] methacrylamide) (P2) or poly(acryloyl hydrazide) imidazole (P3) were synthesised via free radical polymerisation displaying amine groups that cluster cells mediated by electrostatic interactions. This binding resulted in a forced transition from planktonic to a sessile lifestyle. The clustering is accompanied by reduced motility, increased biofilm synthesis and repression of virulence since the expression cholera toxin was down-regulated. This avirulent phenotype was defective to colonise intestinal epithelial cells and the zebrafish digestive tract. Since the cell density increases locally as a result of the clustering, a quorum-sensing-controlled phenotype was observed as the lux operon was actively expressed. Overall, the bacterial physiology was modulated without genetic modification preventing virulence as the pathogen adapt its lifestyle during clustered lifestyle. This thesis highlights the use of polymeric materials as a mean to control pathogens beyond the use antibiotics.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):