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A 16kb naturally occurring genomic deletion including mce and PPE genes in Mycobacterium avium subspecies paratuberculosis isolates from goats with Johne`s disease

Investigation published in Veterinary Microbiology

September 14th, 2012

In this study we characterise the genomic and transcriptomic variability of a natural deletion strain of Mycobacterium avium subspecies paratuberculosis (MAP) prevalent in Spanish Guadarrama goats. Using a pan-genome microarray including MAP and M. avium subspecies hominissuis 104 genomes (MAPAC) we demonstrate the genotype to be MAP Type II with a single deletion of 19 contiguous ORFs (16kb) including a complete mammalian cell entry (mce7_1) operon and adjacent proline-glutamic acid (PE)/proline-proline-glutamic acid (PPE) genes. A deletion specific PCR test was developed and a subsequent screening identified four goat herds infected with the variant strain. Each was located in central Spain and showed epidemiological links suggestive of transmission between herds. A majority of animals infected with the variant manifested a paucibacillary form of the disease. Comparisons between virulent complete genome compliment strains isolated from multibacillary diseased goats and the MAP variant strain during entry into activated macrophages demonstrated an increased sensitivity in the variant to intracellular killing in human and ovine macrophages. As PPE and mce genes are associated with mycobacterial virulence and pathogenesis we investigated the interplay of these gene sets during cell entry using the MAPAC array. This showed significant differential transcriptome profiles compared to full genome complement MAP controls that included changes in other undeleted mce operons and PE/PPE genes, esx-like signalling operons and stress response/fatty acid metabolism pathways. This strain represents the first report of a MAP Type II genotype with significant natural genomic deletions which remains able to cause disease and is transmissible in goats




Castellanos E., Aranaz A., de Juan L., Dominguez L., Linedale R. and Bull TJ.




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A 16kb naturally occurring genomic deletion including mce and PPE genes in Mycobacterium avium subspecies paratuberculosis isolates from goats with Johne`s disease

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A 16kb naturally occurring genomic deletion including mce and PPE genes in Mycobacterium avium subspecies paratuberculosis isolates from goats with Johne`s disease



Participants:

Universidad ComplutenseServicio de Micobacterias (MYC). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM).

Division of Cellular and Molecular Medicine. St George´s University of London (SGUL).

Universidad ComplutenseDepartamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM).







Veterinary Microbiology
FACTOR YEAR Q
3.127 2012

NLMID: 7705469

PMID: 22472702

ISSN: 0378-1135



TITLE: A 16kb naturally occurring genomic deletion including mce and PPE genes in Mycobacterium avium subspecies paratuberculosis isolates from goats with Johne`s disease


JOURNAL: Vet. Microbiol.


NUMERACIÓN: 159(1-2):60-8


AÑO: 2012


PUBLISHER: Elsevier Science Publishers


AUTHORS: Castellanos E., Aranaz A., de Juan L., Dominguez L., Linedale R. and Bull TJ.


VISAVET PARTICIPANTS


3rd
Lucía de Juan Ferré
4th
Lucas Domínguez Rodríguez

DOI: https://doi.org/10.1016/j.vetmic.2012.03.010


CITE THIS PUBLICATION:

Castellanos E., Aranaz A., de Juan L., Dominguez L., Linedale R. and Bull TJ. A 16kb naturally occurring genomic deletion including mce and PPE genes in Mycobacterium avium subspecies paratuberculosis isolates from goats with Johne`s disease. Veterinary Microbiology. 159(1-2):60-8. 2012. (A). ISSN: 0378-1135. DOI: 10.1016/j.vetmic.2012.03.010


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