Mutations in pneumococcal cpsE generated via in vitro serial passaging reveal a potential mechanism of reduced encapsulation utilized by a conjunctival isolate

Journal of Bacteriology
Mara G ShainheitAndrew Camilli

Abstract

The polysaccharide capsule of Streptococcus pneumoniae is required for nasopharyngeal colonization and for invasive disease in the lungs, blood, and meninges. In contrast, the vast majority of conjunctival isolates are acapsular. The first serotype-specific gene in the capsule operon, cpsE, encodes the initiating glycosyltransferase and is one of the few serotype-specific genes that can tolerate null mutations. This report characterizes a spontaneously arising TIGR4 mutant exhibiting a reduced capsule, caused by a 6-nucleotide duplication in cpsE which results in duplication of Ala and Ile at positions 45 and 46. This strain (AI45dup) possessed more exposed phosphorylcholine and was hypersusceptible to C3 complement deposition compared to the wild type. Accordingly, the mutant was significantly better at forming abiotic biofilms and binding epithelial cells in vitro but was avirulent in a sepsis model. In vitro serial passaging of the wild-type strain failed to reproduce the AI45dup mutation but instead led to a variety of mutants with reduced capsule harboring single nucleotide polymorphisms (SNPs) in cpsE. A single passage in the sepsis model after high-dose inoculation readily yielded revertants of AI45dup with restored wild...Continue Reading

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Citations

Jul 6, 2016·Nucleic Acids Research·Joseph S SchoenigerKelly P Williams
Oct 22, 2016·Molecular Microbiology·Eleanor Fleming, Andrew Camilli
Apr 19, 2017·The Journal of Biological Chemistry·Ann E LinLars Bode
Oct 13, 2019·The Journal of Infectious Diseases·Moon H NahmFeroze Ganaie
Jul 2, 2017·Molecular Biotechnology·Maria DimopoulouMarguerite Dols-Lafargue
Jun 5, 2017·Scientific Reports·Watcharapong MitsuwanManuel J Rodríguez-Ortega
Mar 31, 2018·Frontiers in Microbiology·Sandra M CarvalhoAna R Neves

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