title: Accumulation of Peptidoglycan O-Acetylation Leads to Altered Cell Wall Biochemistry and Negatively Impacts Pathogenesis Factors of Campylobacter jejuni.
abstract: Campylobacter jejuni is a leading cause of bacterial gastroenteritis in the developed world. Despite its prevalence, its mechanisms of pathogenesis are poorly understood. Peptidoglycan (PG) is important for helical shape, colonization, and host-pathogen interactions in C. jejuni Therefore, changes in PG greatly impact the physiology of this organism. O-acetylation of peptidoglycan (OAP) is a bacterial phenomenon proposed to be important for proper cell growth, characterized by acetylation of the C6 hydroxyl group of N-acetylmuramic acid in the PG glycan backbone. The OAP gene cluster consists of a PG O-acetyltransferase A (patA) for translocation of acetate into the periplasm, a PG O-acetyltransferase B (patB) for O-acetylation, and an O-acetylpeptidoglycan esterase (ape1) for de-O-acetylation. In this study, reduced OAP in ΔpatA and ΔpatB had minimal impact on C. jejuni growth and fitness under the conditions tested. However, accumulation of OAP in Δape1 resulted in marked differences in PG biochemistry, including O-acetylation, anhydromuropeptide levels, and changes not expected to result directly from Ape1 activity. This suggests that OAP may be a form of substrate level regulation in PG biosynthesis. Ape1 acetylesterase activity was confirmed in vitro using p-nitrophenyl acetate and O-acetylated PG as substrates. In addition, Δape1 exhibited defects in pathogenesis-associated phenotypes, including cell shape, motility, biofilm formation, cell surface hydrophobicity, and sodium deoxycholate sensitivity. Δape1 was also impaired for chick colonization and adhesion, invasion, intracellular survival, and induction of IL-8 production in INT407 cells in vitro The importance of Ape1 in C. jejuni biology makes it a good candidate as an antimicrobial target.
authors.affiliation: From the Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Reuben
authors.initials: R
authors.lastname: Ha
authors.affiliation: From the Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Emilisa
authors.initials: E
authors.lastname: Frirdich
authors.affiliation: the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Sychantha
authors.affiliation: the Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4AX, United Kingdom, and.
authors.forename: Jacob
authors.initials: J
authors.lastname: Biboy
authors.affiliation: the Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Taveirne
authors.affiliation: the Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109.
authors.forename: Jeremiah G
authors.initials: JG
authors.lastname: Johnson
authors.affiliation: the Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan 48109.
authors.forename: Victor J
authors.initials: VJ
authors.lastname: DiRita
authors.affiliation: the Centre for Bacterial Cell Biology, Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4AX, United Kingdom, and.
authors.forename: Waldemar
authors.initials: W
authors.lastname: Vollmer
authors.affiliation: the Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario N1G 2W1, Canada.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Clarke
authors.affiliation: From the Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada, egaynor@mail.ubc.ca.
authors.forename: Erin C
authors.initials: EC
authors.lastname: Gaynor
mesh_terms: D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D016123:Campylobacter jejuni / Q000235:genetics / Q000378:metabolism* / Q000472:pathogenicity*; D002473:Cell Wall / Q000235:genetics / Q000378:metabolism*; D010457:Peptidoglycan / Q000235:genetics / Q000378:metabolism*; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D010457:Peptidoglycan; D037521:Virulence Factors; D000123:Acetyltransferases
keywords: Campylobacter jejuni; O-Acetylation; O-Acetylesterase; acetylation; bacterial pathogenesis; cell wall; gram-negative bacteria; peptidoglycan