Peptidoglycan LD-Carboxypeptidase Pgp2 Influences Campylobacter jejuni Helical Cell Shape and Pathogenic Properties, and Provides the Substrate for the DL-Carboxypeptidase Pgp1 [Cell Biology]

January 6th, 2014 by Frirdich, E., Vermeulen, J., Biboy, J., Soares, F., Taveirne, M. E., Johnson, J. G., DiRita, V. J., Girardin, S. E., Vollmer, W., Gaynor, E. C.

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. Bioinformatical 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 semi-solid 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 to 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 clarify how PG structure and cell shape impact pathogenic attributes.
  • Posted in Journal of Biological Chemistry, Publications
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