Comparative genome analysis of Mycobacterium avium revealed genetic diversity in strains that cause pulmonary and disseminated disease

PLoS One. 2013 Aug 21;8(8):e71831. doi: 10.1371/journal.pone.0071831. eCollection 2013.


Mycobacterium avium complex (MAC) infection causes disseminated disease in immunocompromised hosts, such as human immunodeficiency virus (HIV)-positive patients, and pulmonary disease in persons without systemic immunosuppression, which has been increasing in many countries. In Japan, the incidence of pulmonary MAC disease caused by M. avium is about 7 times higher than that caused by M. intracellulare. To explore the bacterial factors that affect the pathological state of MAC disease caused by M. avium, we determined the complete genome sequence of the previously unreported M. avium subsp. hominissuis strain TH135 isolated from a HIV-negative patient with pulmonary MAC disease and compared it with the known genomic sequence of M. avium strain 104 derived from an acquired immunodeficiency syndrome patient with MAC disease. The genome of strain TH135 consists of a 4,951,217-bp circular chromosome with 4,636 coding sequences. Comparative analysis revealed that 4,012 genes are shared between the two strains, and strains TH135 and 104 have 624 and 1,108 unique genes, respectively. Many strain-specific regions including virulence-associated genes were found in genomes of both strains, and except for some regions, the G+C content in the specific regions was low compared with the mean G+C content of the corresponding chromosome. Screening of clinical isolates for genes located in the strain-specific regions revealed that the detection rates of strain TH135-specific genes were relatively high in specimens isolated from pulmonary MAC disease patients, while, those of strain 104-specific genes were relatively high in those from HIV-positive patients. Collectively, M. avium strains that cause pulmonary and disseminated disease possess genetically distinct features, and it suggests that the acquisition of specific genes during strain evolution has played an important role in the pathological manifestations of MAC disease.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acquired Immunodeficiency Syndrome / complications
  • Acquired Immunodeficiency Syndrome / microbiology*
  • Bacterial Proteins / genetics
  • Base Composition / genetics
  • Chromosomes, Bacterial / genetics
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics
  • DNA, Circular / chemistry
  • DNA, Circular / genetics
  • Genes, Bacterial / genetics
  • Genetic Variation*
  • Genome, Bacterial / genetics
  • Genomics / methods*
  • Humans
  • Lung Diseases / complications
  • Lung Diseases / microbiology*
  • Molecular Sequence Data
  • Mycobacterium avium Complex / classification
  • Mycobacterium avium Complex / genetics*
  • Mycobacterium avium Complex / pathogenicity
  • Mycobacterium avium-intracellulare Infection / complications
  • Mycobacterium avium-intracellulare Infection / microbiology*
  • Polymerase Chain Reaction
  • Sequence Analysis, DNA
  • Species Specificity
  • Virulence / genetics


  • Bacterial Proteins
  • DNA, Bacterial
  • DNA, Circular

Associated data

  • GENBANK/AP012555

Grants and funding

This work was supported by JSPS KAKENHI Grant Number 24590164 and Grant-in-Aid for Specially Promoted Research of Meijo University Research Institute (to K.U.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.