title: Listeria monocytogenes wall teichoic acid decoration in virulence and cell-to-cell spread.
abstract: 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.
authors.affiliation: Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27606, USA.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Spears
authors.affiliation: Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27606, USA.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Havell
authors.affiliation: Department of Microbiology and Immunology, School of Osteopathic Medicine, Campbell University, Buies Creek, NC, 27506, USA.
authors.forename: Terri S
authors.initials: TS
authors.lastname: Hamrick
authors.affiliation: Department of Microbiology and Immunology, School of Osteopathic Medicine, Campbell University, Buies Creek, NC, 27506, USA.
authors.forename: John B
authors.initials: JB
authors.lastname: Goforth
authors.affiliation: Department of Microbiology and Immunology, School of Osteopathic Medicine, Campbell University, Buies Creek, NC, 27506, USA.
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Levine
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy & Health Sciences, Campbell University, Buies Creek, NC, 27506, USA.
authors.forename: S Thomas
authors.initials: ST
authors.lastname: Abraham
authors.affiliation: Complex Carbohydrate Research Center, The University of Georgia, Athens, GA, 30602, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.affiliation: Complex Carbohydrate Research Center, The University of Georgia, Athens, GA, 30602, USA.
authors.forename: Parastoo
authors.initials: P
authors.lastname: Azadi
authors.affiliation: Department of Population Health and Pathobiology, College of Veterinary Medicine, North Carolina State University, Raleigh, NC, 27606, USA.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Orndorff
mesh_terms: D000818:Animals; D001435:Bacteriophages / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D005260:Female; D008089:Listeria monocytogenes / Q000378:metabolism* / Q000472:pathogenicity*; D008088:Listeriosis / Q000382:microbiology; D008099:Liver / Q000382:microbiology; D051379:Mice; D009154:Mutation; D010457:Peptidoglycan / Q000378:metabolism; D013154:Spleen / Q000382:microbiology; D013682:Teichoic Acids / Q000378:metabolism*; D014774:Virulence
chemical_list: D010457:Peptidoglycan; D013682:Teichoic Acids