An Engineered Synthetic Biologic Protects Against Clostridium difficile Infection

Frontiers in Microbiology
Gayatri VedantamV K Viswanathan

Abstract

Morbidity and mortality attributed to Clostridium difficile infection (CDI) have increased over the past 20 years. Currently, antibiotics are the only US FDA-approved treatment for primary C. difficile infection, and these are, ironically, associated with disease relapse and the threat of burgeoning drug resistance. We previously showed that non-toxin virulence factors play key roles in CDI, and that colonization factors are critical for disease. Specifically, a C. difficile adhesin, Surface Layer Protein A (SlpA) is a major contributor to host cell attachment. In this work, we engineered Syn-LAB 2.0 and Syn-LAB 2.1, two synthetic biologic agents derived from lactic acid bacteria, to stably and constitutively express a host-cell binding fragment of the C. difficile adhesin SlpA on their cell-surface. Both agents harbor conditional suicide plasmids expressing a codon-optimized chimera of the lactic acid bacterium's cell-wall anchoring surface-protein domain, fused to the conserved, highly adherent, host-cell-binding domain of C. difficile SlpA. Both agents also incorporate engineered biocontrol, obviating the need for any antibiotic selection. Syn-LAB 2.0 and Syn-LAB 2.1 possess positive biophysical and in vivo properties compar...Continue Reading

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Citations

Jan 11, 2020·Frontiers in Microbiology·Xianping LiZhihong Ren
Nov 19, 2021·Expert Opinion on Therapeutic Targets·Tanya M MonaghanWeng C Chan

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Datasets Mentioned

BETA
CP000033.3

Methods Mentioned

BETA
PCR
dot blot
flow cytometry
Fluorescence-activating cell sorting
electrophoresis

Software Mentioned

FACSDiva
Excel
Stat

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