Journal article
Accumulation of Peptidoglycan O-Acetylation Leads to Altered Cell Wall Biochemistry and Negatively Impacts Pathogenesis Factors of Campylobacter jejuni
The Journal of biological chemistry, Vol.291(43), pp.22686-22702
10/21/2016
DOI: 10.1074/jbc.M116.746404
PMCID: PMC5077204
PMID: 27474744
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.
Details
- Title: Subtitle
- Accumulation of Peptidoglycan O-Acetylation Leads to Altered Cell Wall Biochemistry and Negatively Impacts Pathogenesis Factors of Campylobacter jejuni
- Creators
- Reuben Ha - University of British ColumbiaEmilisa Frirdich - University of British ColumbiaDavid Sychantha - University of GuelphJacob Biboy - Newcastle UniversityMichael E. Taveirne - University of Michigan–Ann ArborJeremiah G. Johnson - University of Michigan–Ann ArborVictor J. DiRita - University of Michigan–Ann ArborWaldemar Vollmer - Newcastle UniversityAnthony J. Clarke - University of GuelphErin C. Gaynor - University of British Columbia
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.291(43), pp.22686-22702
- Publisher
- Elsevier Inc
- DOI
- 10.1074/jbc.M116.746404
- PMID
- 27474744
- PMCID
- PMC5077204
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Language
- English
- Date published
- 10/21/2016
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984696567602771
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