A New Family of Capsule Polymerases Generates Teichoic Acid-Like Capsule Polymers in Gram-Negative Pathogens

MBio
Christa LitschkoTimm Fiebig

Abstract

Group 2 capsule polymers represent crucial virulence factors of Gram-negative pathogenic bacteria. They are synthesized by enzymes called capsule polymerases. In this report, we describe a new family of polymerases that combine glycosyltransferase and hexose- and polyol-phosphate transferase activity to generate complex poly(oligosaccharide phosphate) and poly(glycosylpolyol phosphate) polymers, the latter of which display similarity to wall teichoic acid (WTA), a cell wall component of Gram-positive bacteria. Using modeling and multiple-sequence alignment, we showed homology between the predicted polymerase domains and WTA type I biosynthesis enzymes, creating a link between Gram-negative and Gram-positive cell wall biosynthesis processes. The polymerases of the new family are highly abundant and found in a variety of capsule-expressing pathogens such as Neisseria meningitidis, Actinobacillus pleuropneumoniae, Haemophilus influenzae, Bibersteinia trehalosi, and Escherichia coli with both human and animal hosts. Five representative candidates were purified, their activities were confirmed using nuclear magnetic resonance (NMR) spectroscopy, and their predicted folds were validated by site-directed mutagenesis.IMPORTANCE Bacteri...Continue Reading

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Citations

Jul 19, 2020·Annual Review of Microbiology·Chris WhitfieldCaitlin Sande
Mar 11, 2020·Nature Chemical Biology·Bradley R ClarkeChris Whitfield
Sep 20, 2020·Nature Communications·Timm FiebigMartina Mühlenhoff
Dec 10, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Satu Mikkola
Jul 19, 2021·Trends in Microbiology·Sohyoung LeeJeongmin Song

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Datasets Mentioned

BETA
AEC50903.1
AAQ12660.1
OAQ14264.1
KY798410
KY807157
ACE62291.1
AY496881.1
were

Methods Mentioned

BETA
phosphotransferase
nuclear magnetic resonance
size exclusion chromatography
electrophoresis
NMR
total correlation spectroscopy
PCR
gel filtration

Software Mentioned

TopSpin
Clustal Omega
PHYRE2
BLAST

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