DNA polymorphism of Mycobacterium tuberculosis PE_PGRS33 gene among clinical isolates of pediatric TB patients and its associations with clinical presentation

Abstract

In vitro and in animal studies have suggested an important role for the Mycobacterium tuberculosis PE_PGRS33 protein in the pathogenesis of TB. A significant level of PE_PGRS33 gene DNA polymorphism among clinical isolates from adult tuberculosis (TB) patients and its association with clinical and epidemiological phenotypes of the disease has been found. To better understand the role of PE_PGRS33 protein in the pathogenesis pediatric TB, we investigated DNA polymorphism of the PE_PGRS33 gene among 101 of pediatric TB patients' isolates and assessed the relationship between the PE_PGRS33 sequence variation and clinical characteristics of TB. Twelve different PE_PGRS33 sequence variations representing 12 different alleles were observed among the 101 M.tuberculosis clinical isolates investigated. Of these 101 isolates, 62(59.41%) had PE_PGRS33 alleles that would result in a change in the amino acid sequence of the PE_PGRS33 protein. The degree of DNA polymorphism within individual M.tuberculosis isolates from pediatric TB patients was remarkably lower than that previously found in M.tuberculosis isolates from adults TB patients. The frequency distribution of isolates having PE_PGRS33 gene sequence variations was similar between Beijing and non-Beijing families of the pathogen. Patients having TB meningitis and negative PPD skin test results appeared to be more likely to be infected by isolates having a mutant type of the PE_PGRS33 gene than patients who had no TB meningitis (OR 2.54, 95% CI [1.11-5.84]) and patients who had positive PPD-skin test results (OR 4.26, 95% CI [1.14-12.86]), respectively. This study provides new insight into the molecular pathogenesis of pediatric TB.