The Mycobacterium avium ssp. paratuberculosis specific mptD gene is required for maintenance of the metabolic homeostasis necessary for full virulence in mouse infections.

2.50
Hdl Handle:
http://hdl.handle.net/10033/334479
Title:
The Mycobacterium avium ssp. paratuberculosis specific mptD gene is required for maintenance of the metabolic homeostasis necessary for full virulence in mouse infections.
Authors:
Meißner, Thorsten; Eckelt, Elke; Basler, Tina; Meens, Jochen; Heinzmann, Julia; Suwandi, Abdulhadi; Oelemann, Walter M R; Trenkamp, Sandra; Holst, Otto; Weiss, Siegfried; Bunk, Boyke; Spröer, Cathrin; Gerlach, Gerald-F; Goethe, Ralph
Abstract:
Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease, a chronic granulomatous enteritis in ruminants. Furthermore, infections of humans with MAP have been reported and a possible association with Crohn's disease and diabetes type I is currently discussed. MAP owns large sequence polymorphisms (LSPs) that were exclusively found in this mycobacteria species. The relevance of these LSPs in the pathobiology of MAP is still unclear. The mptD gene (MAP3733c) of MAP belongs to a small group of functionally uncharacterized genes, which are not present in any other sequenced mycobacteria species. mptD is part of a predicted operon (mptABCDEF), encoding a putative ATP binding cassette-transporter, located on the MAP-specific LSP14. In the present study, we generated an mptD knockout strain (MAPΔmptD) by specialized transduction. In order to investigate the potential role of mptD in the host, we performed infection experiments with macrophages. By this, we observed a significantly reduced cell number of MAPΔmptD early after infection, indicating that the mutant was hampered with respect to adaptation to the early macrophage environment. This important role of mptD was supported in mouse infection experiments where MAPΔmptD was significantly attenuated after peritoneal challenge. Metabolic profiling was performed to determine the cause for the reduced virulence and identified profound metabolic disorders especially in the lipid metabolism of MAPΔmptD. Overall our data revealed the mptD gene to be an important factor for the metabolic adaptation of MAP required for persistence in the host.
Affiliation:
Department of Infectious Diseases, Institute for Microbiology, University of Veterinary Medicine Hannover Hannover, Germany.
Citation:
The Mycobacterium avium ssp. paratuberculosis specific mptD gene is required for maintenance of the metabolic homeostasis necessary for full virulence in mouse infections. 2014, 4:110 Front Cell Infect Microbiol
Journal:
Frontiers in cellular and infection microbiology
Issue Date:
2014
URI:
http://hdl.handle.net/10033/334479
DOI:
10.3389/fcimb.2014.00110
PubMed ID:
25177550
Type:
Article
Language:
en
ISSN:
2235-2988
Appears in Collections:
publications of the research group molecular Immunology (MOLI)

Full metadata record

DC FieldValue Language
dc.contributor.authorMeißner, Thorstenen
dc.contributor.authorEckelt, Elkeen
dc.contributor.authorBasler, Tinaen
dc.contributor.authorMeens, Jochenen
dc.contributor.authorHeinzmann, Juliaen
dc.contributor.authorSuwandi, Abdulhadien
dc.contributor.authorOelemann, Walter M Ren
dc.contributor.authorTrenkamp, Sandraen
dc.contributor.authorHolst, Ottoen
dc.contributor.authorWeiss, Siegfrieden
dc.contributor.authorBunk, Boykeen
dc.contributor.authorSpröer, Cathrinen
dc.contributor.authorGerlach, Gerald-Fen
dc.contributor.authorGoethe, Ralphen
dc.date.accessioned2014-11-11T12:09:20Z-
dc.date.available2014-11-11T12:09:20Z-
dc.date.issued2014-
dc.identifier.citationThe Mycobacterium avium ssp. paratuberculosis specific mptD gene is required for maintenance of the metabolic homeostasis necessary for full virulence in mouse infections. 2014, 4:110 Front Cell Infect Microbiolen
dc.identifier.issn2235-2988-
dc.identifier.pmid25177550-
dc.identifier.doi10.3389/fcimb.2014.00110-
dc.identifier.urihttp://hdl.handle.net/10033/334479-
dc.description.abstractMycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease, a chronic granulomatous enteritis in ruminants. Furthermore, infections of humans with MAP have been reported and a possible association with Crohn's disease and diabetes type I is currently discussed. MAP owns large sequence polymorphisms (LSPs) that were exclusively found in this mycobacteria species. The relevance of these LSPs in the pathobiology of MAP is still unclear. The mptD gene (MAP3733c) of MAP belongs to a small group of functionally uncharacterized genes, which are not present in any other sequenced mycobacteria species. mptD is part of a predicted operon (mptABCDEF), encoding a putative ATP binding cassette-transporter, located on the MAP-specific LSP14. In the present study, we generated an mptD knockout strain (MAPΔmptD) by specialized transduction. In order to investigate the potential role of mptD in the host, we performed infection experiments with macrophages. By this, we observed a significantly reduced cell number of MAPΔmptD early after infection, indicating that the mutant was hampered with respect to adaptation to the early macrophage environment. This important role of mptD was supported in mouse infection experiments where MAPΔmptD was significantly attenuated after peritoneal challenge. Metabolic profiling was performed to determine the cause for the reduced virulence and identified profound metabolic disorders especially in the lipid metabolism of MAPΔmptD. Overall our data revealed the mptD gene to be an important factor for the metabolic adaptation of MAP required for persistence in the host.en
dc.language.isoenen
dc.titleThe Mycobacterium avium ssp. paratuberculosis specific mptD gene is required for maintenance of the metabolic homeostasis necessary for full virulence in mouse infections.en
dc.typeArticleen
dc.contributor.departmentDepartment of Infectious Diseases, Institute for Microbiology, University of Veterinary Medicine Hannover Hannover, Germany.en
dc.identifier.journalFrontiers in cellular and infection microbiologyen

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