Effect of the deletion of lprG and p55 genes in the K10 strain of Mycobacterium avium subspecies paratuberculosis.

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  • Additional Information
    • Source:
      Publisher: British Veterinary Association Country of Publication: England NLM ID: 0401300 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-2661 (Electronic) Linking ISSN: 00345288 NLM ISO Abbreviation: Res Vet Sci Subsets: MEDLINE
    • Publication Information:
      Publication: London : British Veterinary Association
      Original Publication: Oxford.
    • Subject Terms:
      Gene Deletion*; Bacterial Proteins/*genetics ; Membrane Transport Proteins/*genetics ; Mycobacterium avium subsp. paratuberculosis/*genetics ; Mycobacterium avium subsp. paratuberculosis/*pathogenicity ; Virulence Factors/*genetics; Animals ; Bacterial Proteins/metabolism ; Cattle ; Female ; Macrophages/microbiology ; Membrane Transport Proteins/metabolism ; Mice ; Mice, Inbred BALB C ; Operon ; Virulence/genetics ; Virulence Factors/metabolism
    • Abstract:
      The lprG-p55 operon of Mycobacterium tuberculosis, M. bovis and M. avium strain D4ER has been identified as a virulence factor involved in the transport of toxic compounds. LprG is a lipoprotein that modulates the host immune response against mycobacteria, whereas P55 is an efflux pump that provides resistance to several drugs. In the present study we search for, and characterize, lprg and p55, putative virulence genes in Mycobacterium avium subsp. paratuberculosis (MAP) to generate a live-attenuated strain of MAP that may be useful in the future as live-attenuated vaccine. For this purpose, we generated and evaluated two mutants of MAP strain K10: one mutant lacking the lprG gene (ΔlprG) and the other lacking both genes lprG and p55 (ΔlprG-p55). None of the mutant strains showed altered susceptibility to first-line and second-line antituberculosis drugs or ethidium bromide, only the double mutant had two-fold increase in clarithromycin susceptibility compared with the wild-type strain. The deletion of lprG and of lprG-p55 reduced the replication of MAP in bovine macrophages; however, only the mutant in lprG-p55 grew faster in liquid media and showed reduced viability in macrophages and in a mouse model. Considering that the deletion of both genes lprG-p55, but not that of lprG alone, showed a reduced replication in vivo, we can speculate that p55 contributes to the survival of MAP in this animal model.
      (Copyright © 2021 Elsevier Ltd. All rights reserved.)
    • Contributed Indexing:
      Keywords: Lprg; Mice model; Mycobacterium avium subsp. paratuberculosis mutants; Virulence; bMDM; p55
    • Accession Number:
      0 (Bacterial Proteins)
      0 (Membrane Transport Proteins)
      0 (P55 protein, Mycobacterium)
      0 (Virulence Factors)
    • Publication Date:
      Date Created: 20210604 Date Completed: 20210708 Latest Revision: 20210708
    • Publication Date:
      20221213
    • Accession Number:
      10.1016/j.rvsc.2021.05.019
    • Accession Number:
      34087563