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Listeria monocytogenes wall teichoic acid decoration in virulence and cell‐to‐cell spread

Journal Article · · Molecular Microbiology
DOI:https://doi.org/10.1111/mmi.13353· OSTI ID:1400545
 [1];  [1];  [2];  [2];  [2];  [3];  [4];  [4];  [1]
  1. Department of Population Health and Pathobiology, College of Veterinary Medicine North Carolina State University Raleigh NC 27606 USA
  2. Department of Microbiology and Immunology, School of Osteopathic Medicine Campbell University Buies Creek NC 27506 USA
  3. Department of Pharmaceutical Sciences, College of Pharmacy &, Health Sciences Campbell University Buies Creek NC 27506 USA
  4. Complex Carbohydrate Research Center, The University of Georgia Athens GA 30602 USA

Summary

Wall teichoic acid (WTA) comprises a class of glycopolymers covalently attached to the peptidoglycan of gram positive bacteria. In Listeria monocytogenes , mutations that prevent addition of certain WTA decorating sugars are attenuating. However, the steps required for decoration and the pathogenic process interrupted are not well described. We systematically examined the requirement for WTA galactosylation in a mouse oral‐virulent strain by first creating mutations in four genes whose products conferred resistance to a WTA‐binding bacteriophage. WTA biochemical and structural studies indicated that galactosylated WTA was directly required for bacteriophage adsorption and that mutant WTA lacked appreciable galactose in all except one mutant – which retained a level ca. 7% of the parent. All mutants were profoundly attenuated in orally infected mice and were impaired in cell‐to‐cell spread in vitro. Confocal microscopy of cytosolic mutants revealed that all expressed ActA on their cell surface and formed actin tails with a frequency similar to the parent. However, the mutant tails were significantly shorter – suggesting a defect in actin based motility. Roles for the gene products in WTA galactosylation are proposed. Identification and interruption of WTA decoration pathways may provide a general strategy to discover non‐antibiotic therapeutics for gram positive infections. © 2016 John Wiley & Sons Ltd

Sponsoring Organization:
USDOE
Grant/Contract Number:
FG02-93ER20097
OSTI ID:
1400545
Journal Information:
Molecular Microbiology, Journal Name: Molecular Microbiology Journal Issue: 5 Vol. 101; ISSN 0950-382X
Publisher:
Wiley-BlackwellCopyright Statement
Country of Publication:
FAO
Language:
English

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