Association of Mycobacterium tuberculosis PE PGRS33 polymorphism with clinical and epidemiological characteristics

Sarah Talarico1, M Donald Cave, Betsy Foxman

  • 1Department of Epidemiology, School of Public Health, University of Michigan, 109 Observatory Street, 4648 SPH I, Ann Arbor, MI 48109, USA.

Insights

Genetic variations in the Mycobacterium tuberculosis PE PGRS33 gene impact bacterial persistence. Altered PE PGRS33 alleles in clinical isolates correlated with specific transmission patterns and disease characteristics, suggesting a role in M. tuberculosis persistence.

Area of Science:

  • Microbiology
  • Genetics
  • Infectious Diseases

Background:

  • The PE PGRS gene subfamily of Mycobacterium tuberculosis is implicated in bacterial persistence.
  • The specific role of naturally occurring genetic variations in the PE PGRS33 gene on M. tuberculosis virulence and transmissibility remains unclear.

Purpose of the Study:

  • To investigate the impact of genetic variations in the PE PGRS33 gene on the virulence and transmissibility of clinical M. tuberculosis isolates.
  • To associate PE PGRS33 alleles with clinical and epidemiological characteristics of tuberculosis.

Main Methods:

  • PCR and DNA sequencing were used to identify genetic variations in the PE PGRS33 gene from 649 clinical M. tuberculosis isolates.
  • PE PGRS33 alleles were categorized based on their predicted effect on the protein structure.
  • Multivariate logistic regression was employed to analyze associations with clinical and epidemiological data, controlling for host factors.

Main Results:

  • Approximately 21.8% of isolates (139/639) exhibited PE PGRS33 alleles with significant protein alterations (large insertions/deletions or frameshifts).
  • These isolates with altered PE PGRS33 showed significant associations with genotypic clustering and absence of pulmonary cavitations.
  • Isolates with PE PGRS33 alleles causing no or minimal protein change served as the comparison group.

Conclusions:

  • Significant alterations in the PE PGRS33 gene are associated with specific clinical and epidemiological features of tuberculosis.
  • These findings suggest that the PE PGRS33 gene plays a crucial role in the persistence of Mycobacterium tuberculosis.
  • Further research into PE PGRS33's function could reveal new therapeutic targets for tuberculosis.

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