The Campylobacter jejuni helical to coccoid transition involves changes to peptidoglycan and ability to elicit an immune response

Authors: FRIRDICH, EMILISA - University Of British Columbia; BIBOY, JACOB - Newcastle University; PRYJMA, MARK - University Of British Columbia; LEE, JOOEUN - University Of Toronto; Huynh, Steven; Parker, Craig; GIRARDIN, STEPHEN - University Of Toronto; VOLLMER, WALDEMAR - Newcastle University; GAYNOR, ERIN - University Of British Columbia

Submitted to: Molecular Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/2/2019
Publication Date: 5/9/2019
Citation: Frirdich, E., Biboy, J., Pryjma, M., Lee, J., Huynh, S., Parker, C., Girardin, S.E., Vollmer, W., Gaynor, E.C. 2019. The Campylobacter jejuni helical to coccoid transition involves changes to peptidoglycan and ability to elicit an immune response. Molecular Microbiology. 112(1):280-301. https://doi.org/10.1111/mmi.14269.
DOI: https://doi.org/10.1111/mmi.14269

Interpretive Summary: Bacteria come in a wide variety of shapes and sizes. Shape and size are generally conserved within a genus, and elaborate mechanisms exist to ensure that bacteria maintain their shape during growth and division, indicating that morphology provides selective advantages to different growth environments and affects the biology of the organism. Campylobacter jejuni is a prevalent enteric pathogen that changes morphology from helical to coccoid under unfavorable conditions. Bacterial peptidoglycan maintains cell shape. As C. jejuni transformed from helical to coccoid, peptidoglycan dipeptides increased and tri- and tetrapeptides decreased. The DL-carboxypeptidase Pgp1 important for C. jejuni helical morphology and putative N-acetylmuramoyl-L-alanyl amidase AmiA were both involved in the coccoid transition. Mutants in pgp1 and amiA showed reduced coccoid formation, with delta pgp1 delta amiA producing minimal coccoids. Both delta amiA and delta amiA delta pgp1 lacked flagella and formed unseparated chains of cells consistent with a role for AmiA in cell separation. All strains accumulated PG dipeptides over time, but only strains capable of becoming coccoid displayed tripeptide changes. C. jejuni helical shape and corresponding peptidoglycan structure are important for pathogenesis-related attributes. Concomitantly, changing to a coccoid morphology resulted in differences in pathogenic properties; coccoid C. jejuni were non-motile and non-infectious, with minimal adherence and invasion of epithelial cells and an inability to stimulate IL-8. Coccoid PG exhibited reduced activation of innate immune receptors Nod1 and Nod2 versus helical PG. C. jejuni also transitioned to coccoid within epithelial cells, so the inability of the immune system to detect coccoid C. jejuni may be significant in its pathogenesis.

Technical Abstract: Campylobacter jejuni is a prevalent enteric pathogen that changes morphology from helical to coccoid under unfavorable conditions. Bacterial peptidoglycan maintains cell shape. As C. jejuni transformed from helical to coccoid, peptidoglycan dipeptides increased and tri- and tetrapeptides decreased. The DL-carboxypeptidase Pgp1 important for C. jejuni helical morphology and putative N-acetylmuramoyl-L-alanyl amidase AmiA were both involved in the coccoid transition. Mutants in pgp1 and amiA showed reduced coccoid formation, with delta pgp1 delta amiA producing minimal coccoids. Both delta amiA and delta amiA delta pgp1 lacked flagella and formed unseparated chains of cells consistent with a role for AmiA in cell separation. All strains accumulated PG dipeptides over time, but only strains capable of becoming coccoid displayed tripeptide changes. C. jejuni helical shape and corresponding peptidoglycan structure are important for pathogenesis-related attributes. Concomitantly, changing to a coccoid morphology resulted in differences in pathogenic properties; coccoid C. jejuni were non-motile and non-infectious, with minimal adherence and invasion of epithelial cells and an inability to stimulate IL-8. Coccoid PG exhibited reduced activation of innate immune receptors Nod1 and Nod2 versus helical PG. C. jejuni also transitioned to coccoid within epithelial cells, so the inability of the immune system to detect coccoid C. jejuni may be significant in its pathogenesis.