Mycoplasma hyopneumoniae surface-associated proteases cleave bradykinin, substance P, neurokinin A and neuropeptide Y

Veronica Maria Jarocki; Benjamin Bernard Armando Raymond; Jessica Leigh Tacchi; Matthew Paul Padula; Steven Philip Djordjevic

doi:10.1038/s41598-019-51116-w

Mycoplasma hyopneumoniae surface-associated proteases cleave bradykinin, substance P, neurokinin A and neuropeptide Y

Sci Rep. 2019 Oct 10;9(1):14585. doi: 10.1038/s41598-019-51116-w.

Authors

Veronica Maria Jarocki¹, Benjamin Bernard Armando Raymond², Jessica Leigh Tacchi², Matthew Paul Padula³, Steven Philip Djordjevic^{4

5}

Affiliations

¹ ithree institute, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia. veronica.jarocki@uts.edu.au.
² ithree institute, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia.
³ Proteomics Core Facility, University of Technology Sydney, PO Box 123, Broadway, 2007, NSW, Australia.
⁴ ithree institute, University of Technology Sydney, PO Box 123, Broadway, NSW, 2007, Australia. steven.djordjevic@uts.edu.au.
⁵ Proteomics Core Facility, University of Technology Sydney, PO Box 123, Broadway, 2007, NSW, Australia. steven.djordjevic@uts.edu.au.

Abstract

Mycoplasma hyopneumoniae is an economically-devastating and geographically-widespread pathogen that colonises ciliated epithelium, and destroys mucociliary function. M. hyopneumoniae devotes ~5% of its reduced genome to encode members of the P97 and P102 adhesin families that are critical for colonising epithelial cilia, but mechanisms to impair mucociliary clearance and manipulate host immune response to induce a chronic infectious state have remained elusive. Here we identified two surface exposed M. hyopneumoniae proteases, a putative Xaa-Pro aminopeptidase (MHJ_0659; PepP) and a putative oligoendopeptidase F (MHJ_0522; PepF), using immunofluorescence microscopy and two orthogonal proteomic methodologies. MHJ_0659 and MHJ_0522 were purified as polyhistidine fusion proteins and shown, using a novel MALDI-TOF MS assay, to degrade four pro-inflammatory peptides that regulate lung homeostasis; bradykinin (BK), substance P (SP), neurokinin A (NKA) and neuropeptide Y (NPY). These findings provide insight into the mechanisms used by M. hyopneumoniae to influence ciliary beat frequency, impair mucociliary clearance, and initiate a chronic infectious disease state in swine, features that are a hallmark of disease caused by this pathogen.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adhesins, Bacterial / metabolism
Aminopeptidases / metabolism*
Animals
Bacterial Proteins / metabolism*
Bradykinin / chemistry*
Immunity, Innate
Metalloendopeptidases / metabolism*
Mycoplasma hyopneumoniae / enzymology*
Neurokinin A / chemistry*
Neuropeptide Y / chemistry*
Proteomics
Substance P / chemistry*
Swine
Trypsin / chemistry

Substances

Adhesins, Bacterial
Bacterial Proteins
Neuropeptide Y
Substance P
Neurokinin A
Aminopeptidases
Trypsin
Metalloendopeptidases
Oligoendopeptidase F
Bradykinin