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Updated: Jul 15, 2026

Demonstrating a Multi-drug Resistant Mycobacterium tuberculosis Amplification Microarray
Published on: April 25, 2014
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.
Abstract:
There is evidence that some members of the Mycobacterium tuberculosis PE PGRS gene subfamily, including PE PGRS33, may have a specific function in M. tuberculosis persistence. The impact of naturally-occurring PE PGRS33 genetic variations on the virulence and transmissibility of clinical M. tuberculosis isolates is not known. We used PCR and DNA sequencing to identify genetic variations in the PE PGRS33 gene in comparison with the sequenced laboratory strain, H37Rv, among 649 isolates from a population-based sample. The PE PGRS33 alleles were placed into two groups, based on the effect of the sequence variations on the PE PGRS33 protein, and their associations with clinical and epidemiological characteristics were assessed using multivariate logistic regression to control for potential confounding of host-related factors. Of the 639 isolates for which sequence data were obtained, 139 (21.8%) had PE PGRS33 alleles that would result in a significant change to the PE PGRS33 protein due to large insertions/deletions or frameshift mutations. These isolates were significantly associated with clustering based on genotype and absence of cavitations in the lungs, compared to isolates having PE PGRS33 alleles that would result in no or minimal change to the PE PGRS33 protein. The association of significant changes to PE PGRS33 with clinical and epidemiological characteristics suggests that PE PGRS33 may have an important role in M. tuberculosis persistence.
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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