using-protozoan-paramecium-caudatum-as-vehicle-for-food-borne

Using the Protozoan <em>Paramecium caudatum</em> as a Vehicle for Food-borne Infections in Zebrafish Larvae

Due to their transparency, genetic tractability, and ease of maintenance, zebrafish (Danio rerio) have become a widely-used vertebrate model for ...

University of Texas Health Science Center at Houston

Here we report the first application of non-bactericidal synthetic polymers to modulate the physiology of a bacterial pathogen. Poly(-[3-(dimethylamino)propyl] methacrylamide) () and poly(-(3-aminopropyl)methacrylamide) (), cationic polymers that bind to the surface of , the infectious agent causing cholera disease, can sequester the pathogen into clusters. Upon clustering,  transitions to a sessile lifestyle, characterised by increased biofilm production and the repression of key virulence factors such as the cholera toxin (CTX). Moreover, clustering the pathogen results in the minimisation of adherence and toxicity to intestinal epithelial cells. Our results suggest that the reduction in toxicity is associated with the reduction to the number of free bacteria, but also the downregulation of toxin production. Finally we demonstrate that these polymers can reduce colonisation of zebrafish larvae upon ingestion of water contaminated with . Overall, our results suggest that the physiology of this pathogen can be modulated without the need to genetically manipulate the microorganism and that this modulation is an off-target effect that results from the intrinsic ability of the pathogen to sense and adapt to its environment. We believe these findings pave the way towards a better understanding of the interactions between pathogenic bacteria and polymeric materials and will underpin the development of novel antimicrobial polymers.

Engineering microbial physiology with synthetic polymers: cationic polymers induce biofilm formation in  and downregulate the expression of virulence genes.

Bacterial adhesion to host receptors is an early and essential step in bacterial colonization, and the nature of adhesin-receptor interactions determines bacterial localization and thus the outcome of these interactions. Here, we determined the host receptors for the multivalent adhesion molecule (MAM) from the gut commensal  HS (MAM), which contains an array of seven mammalian cell entry domains. The MAM adhesin interacted with a range of host receptors, through recognition of a shared 3--sulfogalactosyl moiety. This functional group is also found in mucin, a component of the intestinal mucus layer and thus one of the prime adherence targets for commensal  Mucin gels impeded the motility of  by acting as a physical barrier, and the barrier effect was enhanced by specific interactions between mucin and MAM in a sulfation-dependent manner. Desulfation of mucin by pure sulfatase or the sulfatase-producing commensal  decreased binding of  to mucin and increased the attachment of bacteria to the epithelial surface via interactions with surface-localized sulfated lipid and protein receptors. Together, our results demonstrate that the  adhesin MAM facilitates retention of a gut commensal by attachment to mucin. They further suggest that the amount of sulfatase secreted by mucin-foraging bacteria such as , inhabiting the same niche, may affect the capacity of the mucus barrier to retain commensal .

3-Sulfogalactosyl-dependent adhesion of  HS multivalent adhesion molecule is attenuated by sulfatase activity.

[This corrects the article DOI: 10.1039/C7SC00615B.].

Correction: Engineering microbial physiology with synthetic polymers: cationic polymers induce biofilm formation in  and downregulate the expression of virulence genes.

Article	Year
Engineering microbial physiology with synthetic polymers: cationic polymers induce biofilm formation in and downregulate the expression of virulence genes. Chemical science\| PubMed ID: 28970909	2017
3-Sulfogalactosyl-dependent adhesion of HS multivalent adhesion molecule is attenuated by sulfatase activity. The Journal of biological chemistry\| PubMed ID: 28982977	2017
Correction: Engineering microbial physiology with synthetic polymers: cationic polymers induce biofilm formation in and downregulate the expression of virulence genes. Chemical science\| PubMed ID: 30393533	2018

Anne-Marie Krachler

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