Characterization of cleavage events in the multifunctional cilium adhesin Mhp684 (P146) reveals a mechanism by which mycoplasma hyopneumoniae regulates surface topography

Article


Bogema, Daniel R., Deutscher, Ania T., Woolley, Lauren K., Seymour, Lisa M., Raymond, Benjamin B. A., Tacchi, Jessica L., Padula, Matthew P., Dixon, Nicholas E., Minion, F. Chris, Jenkins, Cheryl, Walker, Mark J. and Djordjevic, Steven P.. 2012. "Characterization of cleavage events in the multifunctional cilium adhesin Mhp684 (P146) reveals a mechanism by which mycoplasma hyopneumoniae regulates surface topography." mBio. 3 (2), pp. 1-12. https://doi.org/10.1128/mBio.00282-11
Article Title

Characterization of cleavage events in the multifunctional cilium adhesin Mhp684 (P146) reveals a mechanism by which mycoplasma hyopneumoniae regulates surface topography

ERA Journal ID123204
Article CategoryArticle
AuthorsBogema, Daniel R. (Author), Deutscher, Ania T. (Author), Woolley, Lauren K. (Author), Seymour, Lisa M. (Author), Raymond, Benjamin B. A. (Author), Tacchi, Jessica L. (Author), Padula, Matthew P. (Author), Dixon, Nicholas E. (Author), Minion, F. Chris (Author), Jenkins, Cheryl (Author), Walker, Mark J. (Author) and Djordjevic, Steven P. (Author)
Journal TitlemBio
Journal Citation3 (2), pp. 1-12
Number of Pages12
Year2012
Place of PublicationWashington, DC. United States
ISSN2150-7511
2161-2129
Digital Object Identifier (DOI)https://doi.org/10.1128/mBio.00282-11
Web Address (URL)http://mbio.asm.org/content/3/2/e00282-11
Abstract

Mycoplasma hyopneumoniae causes enormous economic losses to swine production worldwide by colonizing the ciliated epithelium in the porcine respiratory tract, resulting in widespread damage to the mucociliary escalator, prolonged inflammation, reduced weight gain, and secondary infections. Protein Mhp684 (P146) comprises 1,317 amino acids, and while the N-terminal 400 residues display significant sequence identity to the archetype cilium adhesin P97, the remainder of the molecule is novel and displays unusual motifs. Proteome analysis shows that P146 preprotein is endogenously cleaved into three major fragments identified here as P50P146, P40P146, and P85P146 that reside on the cell surface. Liquid chromatography with tandem mass spectrometry (LC-MS/MS) identified a semitryptic peptide that delineated a major cleavage site in Mhp684. Cleavage occurred at the phenylalanine residue within sequence 672ATEF2QQ677, consistent with a cleavage motif resembling S/T-X-F2XD/E recently identified in Mhp683 and other P97/P102 family members. Biotinylated surface proteins recovered by avidin chromatography and separated by two-dimensional gel electrophoresis (2-D GE) showed that more-extensive endoproteolytic cleavage of P146 occurs. Recombinant fragments F1P146-F3P146 that mimic P50P146, P40P146, and P85P146 were constructed and shown to bind porcine epithelial cilia and biotinylated heparin with physiologically relevant affinity. Recombinant versions of F3P146 generated from M. hyopneumoniae strain J and 232 sequences strongly bind porcine plasminogen, and the removal of their respective C-terminal lysine and arginine residues significantly reduces this interaction. These data reveal that P146 is an extensively processed, multifunctional adhesin of M. hyopneumoniae. Extensive cleavage coupled with variable cleavage efficiency provides a mechanism by which M. hyopneumoniae regulates protein topography.

Keywordsadhesins; bacterial; amino acid sequence; pig production; respiratory disease
ANZSRC Field of Research 2020300304. Animal protection (incl. pests and pathogens)
310902. Animal cell and molecular biology
300999. Veterinary sciences not elsewhere classified
Public Notes

© 2012 Bogema et al. This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported License, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original author and source are credited.

Byline AffiliationsDepartment of Primary Industries, New South Wales
University of Wollongong
University of Technology Sydney
Iowa State University, United States
Elizabeth Macarthur Agricultural Institute, Australia
University of Queensland
Institution of OriginUniversity of Southern Queensland
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