Mycoplasma hyopneumoniae resides intracellularly within porcine epithelial cells

Raymond, BBA; Turnbull, L; Jenkins, C; Madhkoor, R; Schleicher, I; Uphoff, CC; Whitchurch, CB; Rohde, M; Djordjevic, SP

Mycoplasma hyopneumoniae resides intracellularly within porcine epithelial cells

Raymond, BBA

Turnbull, L

Jenkins, C

Madhkoor, R Schleicher, I Uphoff, CC Whitchurch, CB

Rohde, M Djordjevic, SP

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Publication Type:: Journal Article
Citation:: Scientific Reports, 2018, 8 (1)
Issue Date:: 2018-12-01

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Field	Value	Language
dc.contributor.author	Raymond, BBA https://orcid.org/0000-0003-3610-9289	en_US
dc.contributor.author	Turnbull, L https://orcid.org/0000-0002-9255-9033	en_US
dc.contributor.author	Jenkins, C https://orcid.org/0000-0002-5966-072X	en_US
dc.contributor.author	Madhkoor, R	en_US
dc.contributor.author	Schleicher, I	en_US
dc.contributor.author	Uphoff, CC	en_US
dc.contributor.author	Whitchurch, CB https://orcid.org/0000-0003-2296-3791	en_US
dc.contributor.author	Rohde, M	en_US
dc.contributor.author	Djordjevic, SP https://orcid.org/0000-0001-9301-5372	en_US
dc.date.available	2018-11-09	en_US
dc.date.issued	2018-12-01	en_US
dc.identifier.citation	Scientific Reports, 2018, 8 (1)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/129385
dc.description.abstract	© 2018, The Author(s). Enzootic pneumonia incurs major economic losses to pork production globally. The primary pathogen and causative agent, Mycoplasma hyopneumoniae, colonises ciliated epithelium and disrupts mucociliary function predisposing the upper respiratory tract to secondary pathogens. Alleviation of disease is reliant on antibiotics, vaccination, and sound animal husbandry, but none are effective at eliminating M. hyopneumoniae from large production systems. Sustainable pork production systems strive to lower reliance on antibiotics but lack of a detailed understanding of the pathobiology of M. hyopneumoniae has curtailed efforts to develop effective mitigation strategies. M. hyopneumoniae is considered an extracellular pathogen. Here we show that M. hyopneumoniae associates with integrin β1 on the surface of epithelial cells via interactions with surface-bound fibronectin and initiates signalling events that stimulate pathogen uptake into clathrin-coated vesicles (CCVs) and caveosomes. These early events allow M. hyopneumoniae to exploit an intracellular lifestyle by commandeering the endosomal pathway. Specifically, we show: (i) using a modified gentamicin protection assay that approximately 8% of M. hyopneumoniae cells reside intracellularly; (ii) integrin β1 expression specifically co-localises with the deposition of fibronectin precisely where M. hyopneumoniae cells assemble extracellularly; (iii) anti-integrin β1 antibodies block entry of M. hyopneumoniae into porcine cells; and (iv) M. hyopneumoniae survives phagolysosomal fusion, and resides within recycling endosomes that are trafficked to the cell membrane. Our data creates a paradigm shift by challenging the long-held view that M. hyopneumoniae is a strict extracellular pathogen and calls for in vivo studies to determine if M. hyopneumoniae can traffic to extrapulmonary sites in commercially-reared pigs.	en_US
dc.relation.ispartof	Scientific Reports	en_US
dc.relation.isbasedon	10.1038/s41598-018-36054-3	en_US
dc.subject.mesh	Cell Membrane	en_US
dc.subject.mesh	Endosomes	en_US
dc.subject.mesh	Epithelial Cells	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Swine	en_US
dc.subject.mesh	Mycoplasma hyopneumoniae	en_US
dc.subject.mesh	Pneumonia of Swine, Mycoplasmal	en_US
dc.subject.mesh	Fibronectins	en_US
dc.subject.mesh	Integrin beta1	en_US
dc.title	Mycoplasma hyopneumoniae resides intracellularly within porcine epithelial cells	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	8	en_US
utslib.for	0601 Biochemistry and Cell Biology	en_US
utslib.for	0702 Animal Production	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	open_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	8	en_US

Abstract:

© 2018, The Author(s). Enzootic pneumonia incurs major economic losses to pork production globally. The primary pathogen and causative agent, Mycoplasma hyopneumoniae, colonises ciliated epithelium and disrupts mucociliary function predisposing the upper respiratory tract to secondary pathogens. Alleviation of disease is reliant on antibiotics, vaccination, and sound animal husbandry, but none are effective at eliminating M. hyopneumoniae from large production systems. Sustainable pork production systems strive to lower reliance on antibiotics but lack of a detailed understanding of the pathobiology of M. hyopneumoniae has curtailed efforts to develop effective mitigation strategies. M. hyopneumoniae is considered an extracellular pathogen. Here we show that M. hyopneumoniae associates with integrin β1 on the surface of epithelial cells via interactions with surface-bound fibronectin and initiates signalling events that stimulate pathogen uptake into clathrin-coated vesicles (CCVs) and caveosomes. These early events allow M. hyopneumoniae to exploit an intracellular lifestyle by commandeering the endosomal pathway. Specifically, we show: (i) using a modified gentamicin protection assay that approximately 8% of M. hyopneumoniae cells reside intracellularly; (ii) integrin β1 expression specifically co-localises with the deposition of fibronectin precisely where M. hyopneumoniae cells assemble extracellularly; (iii) anti-integrin β1 antibodies block entry of M. hyopneumoniae into porcine cells; and (iv) M. hyopneumoniae survives phagolysosomal fusion, and resides within recycling endosomes that are trafficked to the cell membrane. Our data creates a paradigm shift by challenging the long-held view that M. hyopneumoniae is a strict extracellular pathogen and calls for in vivo studies to determine if M. hyopneumoniae can traffic to extrapulmonary sites in commercially-reared pigs.

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http://hdl.handle.net/10453/129385