Journal article
Peptidoglycan ld-Carboxypeptidase Pgp2 Influences Campylobacter jejuni Helical Cell Shape and Pathogenic Properties and Provides the Substrate for the dl-Carboxypeptidase Pgp1
The Journal of biological chemistry, Vol.289(12), pp.8007-8018
03/21/2014
DOI: 10.1074/jbc.M113.491829
PMCID: PMC3961634
PMID: 24394413
Abstract
Despite the importance of Campylobacter jejuni as a pathogen, little is known about the fundamental aspects of its peptidoglycan (PG) structure and factors modulating its helical morphology. A PG dl-carboxypeptidase Pgp1 essential for maintenance of C. jejuni helical shape was recently identified. Bioinformatic analysis revealed the CJJ81176_0915 gene product as co-occurring with Pgp1 in several organisms. Deletion of cjj81176_0915 (renamed pgp2) resulted in straight morphology, representing the second C. jejuni gene affecting cell shape. The PG structure of a Δpgp2 mutant showed an increase in tetrapeptide-containing muropeptides and a complete absence of tripeptides, consistent with ld-carboxypeptidase activity, which was confirmed biochemically. PG analysis of a Δpgp1Δpgp2 double mutant demonstrated that Pgp2 activity is required to generate the tripeptide substrate for Pgp1. Loss of pgp2 affected several pathogenic properties; the deletion strain was defective for motility in semisolid agar, biofilm formation, and fluorescence on calcofluor white. Δpgp2 PG also caused decreased stimulation of the human nucleotide-binding oligomerization domain 1 (Nod1) proinflammatory mediator in comparison with wild type, as expected from the reduction in muropeptide tripeptides (the primary Nod1 agonist) in the mutant; however, these changes did not alter the ability of the Δpgp2 mutant strain to survive within human epithelial cells or to elicit secretion of IL-8 from epithelial cells after infection. The pgp2 mutant also showed significantly reduced fitness in a chick colonization model. Collectively, these analyses enhance our understanding of C. jejuni PG maturation and help to clarify how PG structure and cell shape impact pathogenic attributes.
Background:C. jejuni helical shape is important to pathogenesis.
Results: Deletion of pgp2 results in loss of C. jejuni helical shape and change in peptidoglycan structure and pathogenic properties.
Conclusion: Pgp2 is a ld-carboxypeptidase cleaving peptidoglycan tetrapeptides to tripeptides.
Significance: Characterization of enzymes involved in C. jejuni peptidoglycan and cell shape maintenance is crucial to the understanding of fundamental properties of this organism.
Details
- Title: Subtitle
- Peptidoglycan ld-Carboxypeptidase Pgp2 Influences Campylobacter jejuni Helical Cell Shape and Pathogenic Properties and Provides the Substrate for the dl-Carboxypeptidase Pgp1
- Creators
- Emilisa Frirdich - University of British ColumbiaJenny Vermeulen - University of British ColumbiaJacob Biboy - Newcastle UniversityFraser Soares - University of TorontoMichael E. Taveirne - University of Michigan–Ann ArborJeremiah G. Johnson - University of Michigan–Ann ArborVictor J. DiRita - University of Michigan–Ann ArborStephen E. Girardin - University of TorontoWaldemar Vollmer - Newcastle UniversityErin C. Gaynor - University of British Columbia
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.289(12), pp.8007-8018
- Publisher
- Elsevier Inc
- DOI
- 10.1074/jbc.M113.491829
- PMID
- 24394413
- PMCID
- PMC3961634
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Language
- English
- Date published
- 03/21/2014
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984696726302771
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