Mycobacterium avium subspecies paratuberculosis is able to manipulate host lipid metabolism and accumulate cholesterol within macrophages.

Johansen, MD; de Silva, K; Plain, KM; Whittington, RJ; Purdie, AC

Mycobacterium avium subspecies paratuberculosis is able to manipulate host lipid metabolism and accumulate cholesterol within macrophages.

Johansen, MD de Silva, K Plain, KM Whittington, RJ Purdie, AC

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Publisher:: Elsevier BV
Publication Type:: Journal Article
Citation:: Microbial pathogenesis, 2019, 130, pp. 44-53
Issue Date:: 2019-05

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Field	Value	Language
dc.contributor.author	Johansen, MD
dc.contributor.author	de Silva, K
dc.contributor.author	Plain, KM
dc.contributor.author	Whittington, RJ
dc.contributor.author	Purdie, AC
dc.date.accessioned	2020-05-20T23:47:39Z
dc.date.available	2019-02-26
dc.date.available	2020-05-20T23:47:39Z
dc.date.issued	2019-05
dc.identifier.citation	Microbial pathogenesis, 2019, 130, pp. 44-53
dc.identifier.issn	0882-4010
dc.identifier.issn	1096-1208
dc.identifier.uri	http://hdl.handle.net/10453/140856
dc.description.abstract	Johne's disease is a chronic wasting disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Closely related pathogenic mycobacteria such as M. tuberculosis are capable of altering host lipid metabolism, highlighting the need to explore the role of lipid metabolism contributing to intracellular survival. This study aimed to identify whether MAP is able to manipulate host lipid metabolic pathways and accumulate host cholesterol during early infection. Macrophages were exposed to four different MAP strains and non-pathogenic M. phlei for up to 72 h, with changes to lipid metabolism examined using fluorescent microscopy and gene expression. MAP-infected macrophages displayed strain-dependent differences to intracellular cholesterol levels during early infection, however showed similarly increased intracellular cholesterol at later timepoints. Gene expression revealed that MAP strains similarly activate the host immune response in a conserved manner compared to M. phlei. MAP significantly upregulated host genes associated with lipid efflux and endocytosis. Moreover, lipid biosynthesis genes were differentially regulated in a strain-dependent manner following MAP infection. Collectively, these results demonstrate that MAP manipulates host lipid metabolism during early infection, however the extent of these modulations are strain-dependent. These findings reflect a conserved pathway contributing to intracellular MAP survival.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	Elsevier BV
dc.relation.ispartof	Microbial pathogenesis
dc.relation.isbasedon	10.1016/j.micpath.2019.02.031
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject	0605 Microbiology, 1107 Immunology, 1108 Medical Microbiology
dc.subject.classification	Microbiology
dc.subject.mesh	Macrophages
dc.subject.mesh	Animals
dc.subject.mesh	Mice
dc.subject.mesh	Cholesterol
dc.subject.mesh	Microscopy, Fluorescence
dc.subject.mesh	Gene Expression Profiling
dc.subject.mesh	Endocytosis
dc.subject.mesh	Lipid Metabolism
dc.subject.mesh	Mycobacterium avium subsp. paratuberculosis
dc.subject.mesh	Host-Pathogen Interactions
dc.subject.mesh	RAW 264.7 Cells
dc.subject.mesh	Animals
dc.subject.mesh	Cholesterol
dc.subject.mesh	Endocytosis
dc.subject.mesh	Gene Expression Profiling
dc.subject.mesh	Host-Pathogen Interactions
dc.subject.mesh	Lipid Metabolism
dc.subject.mesh	Macrophages
dc.subject.mesh	Mice
dc.subject.mesh	Microscopy, Fluorescence
dc.subject.mesh	Mycobacterium avium subsp. paratuberculosis
dc.subject.mesh	RAW 264.7 Cells
dc.title	Mycobacterium avium subspecies paratuberculosis is able to manipulate host lipid metabolism and accumulate cholesterol within macrophages.
dc.type	Journal Article
utslib.citation.volume	130
utslib.location.activity	England
utslib.for	0605 Microbiology
utslib.for	1107 Immunology
utslib.for	1108 Medical Microbiology
utslib.for	0605 Microbiology
utslib.for	1107 Immunology
utslib.for	1108 Medical Microbiology
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	/University of Technology Sydney
utslib.copyright.status	closed_access	*
dc.date.updated	2020-05-20T23:47:34Z
pubs.publication-status	Published
pubs.volume	130
utslib.start-page	44

Abstract:

Johne's disease is a chronic wasting disease of ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP). Closely related pathogenic mycobacteria such as M. tuberculosis are capable of altering host lipid metabolism, highlighting the need to explore the role of lipid metabolism contributing to intracellular survival. This study aimed to identify whether MAP is able to manipulate host lipid metabolic pathways and accumulate host cholesterol during early infection. Macrophages were exposed to four different MAP strains and non-pathogenic M. phlei for up to 72 h, with changes to lipid metabolism examined using fluorescent microscopy and gene expression. MAP-infected macrophages displayed strain-dependent differences to intracellular cholesterol levels during early infection, however showed similarly increased intracellular cholesterol at later timepoints. Gene expression revealed that MAP strains similarly activate the host immune response in a conserved manner compared to M. phlei. MAP significantly upregulated host genes associated with lipid efflux and endocytosis. Moreover, lipid biosynthesis genes were differentially regulated in a strain-dependent manner following MAP infection. Collectively, these results demonstrate that MAP manipulates host lipid metabolism during early infection, however the extent of these modulations are strain-dependent. These findings reflect a conserved pathway contributing to intracellular MAP survival.

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http://hdl.handle.net/10453/140856