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Discovery of stable and variable differences in the Mycobacterium avium subsp. paratuberculosis type I, II, and III

Elena Castellanos1, Alicia Aranaz, Katherine A Gould

  • 1Centro de Vigilancia Sanitaria Veterinaria, Departamento Sanidad Animal, Universidad Complutense, Madrid, Spain.

Applied and Environmental Microbiology
|December 3, 2008
PubMed

Insights

Mycobacterium avium subsp. paratuberculosis genomotypes exhibit distinct genomic differences, identified using a novel microarray. These variations impact cell entry genes and immune protein coding, influencing strain characteristics.

Area of Science:

  • Microbiology
  • Genomics
  • Pathogen Research

Background:

  • Mycobacterium avium subsp. paratuberculosis (MAP) is a significant animal pathogen with environmental dissemination.
  • MAP has been linked to Crohn's disease in humans.
  • Three distinct MAP genomotypes are recognized, but their genomic differences require further elucidation.

Purpose of the Study:

  • To investigate and describe the genomic differences among the three major Mycobacterium avium subsp. paratuberculosis genomotypes.
  • To develop and validate a diagnostic tool for differentiating these genomotypes.

Main Methods:

  • Design and validation of a 60-mer oligonucleotide microarray (MAPAC array) based on M. avium subsp. paratuberculosis and M. avium subsp. hominissuis genomes.
  • Identification of large sequence polymorphisms (LSPs) using the MAPAC array.
  • Development of specific PCR assays for diagnostic genes within LSPs.
  • Analysis of insertion/deletion regions (e.g., INDEL12) and variable genomic islands (vGIs).

Main Results:

  • The MAPAC array successfully identified LSPs differentiating the three MAP genomotypes.
  • Type II strains showed reduced genomic content compared to Type I and III, with shared regions with M. avium subsp. hominissuis.
  • PCR assays accurately screened 78 MAP strains.
  • Deletion events in INDEL12 affected mycobacterial cell entry genes and MPT64 protein coding in Type II strains.
  • Variable genomic islands (vGIs) with low GC content and specific flanking sequences were identified, showing signal variations linked to growth rate and morphology.

Conclusions:

  • Genomic characterization using the MAPAC array reveals significant differences between M. avium subsp. paratuberculosis genomotypes.
  • These genomic variations, particularly in cell entry and immune-related genes, may contribute to the distinct characteristics and pathogenicity of different MAP types.
  • Variable genomic islands represent dynamic genomic regions potentially influencing bacterial adaptation and phenotype.

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