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

Impact of pe_pgrs33 Gene Polymorphisms on Mycobacterium tuberculosis Infection and Pathogenesis

“…As shown in Supplementary Table 2, a total of 19 pe_pgrs33 alleles were identified. Apart from the allele referred to as 11, which corresponded to pe_pgrs33 of Mtb H37Rv and was found in 42 MTBC clinical isolates (Figure 1), we identified 11 alleles previously described in literature (Talarico et al, 2005, 2007; Wang et al, 2011; McEvoy et al, 2012) and 7 alleles containing new genetic variations (alleles 3, 7, 8, 9, 14, 16, and 17) compared to pe_pgrs33 of the H37Rv reference strain. Among all pe_pgrs33 alleles, we identified a total of 13 SNPs (9 non-synonymous and 4 synonymous), mainly occurring in the PGRS region.…”

“…Until recently, a possible role of PE_PGRS33 in the antigenic variability of Mtb has been entrenched with the identification of numerous polymorphisms in the pe_pgrs33 gene among Mtb clinical isolates (Talarico et al, 2005, 2007; Wang et al, 2011; McEvoy et al, 2012). However, a recent study questioned this hypothesis, suggesting an ongoing purifying selection on pe_pgrs33 and a limited impact on the functionality and antigenicity of PE_PGRS by indel events occurring in the PGRS domain (Copin et al, 2014).…”

“…The pe_pgrs33 gene from each MTBC clinical strain was amplified with two primers previously described, PE_PGRS33-F1 and PE_PGRS33-R1 (Wang et al, 2011; Supplementary Table 1), by using the Expand High Fidelity PCR System (Roche) kit. Sanger sequencing was performed in Applied Biosystems 3130xl Genetic Analyzer.…”

“…One of the most investigated members of the pe_pgrs gene subfamily, the pe_pgrs33 gene, was shown to be polymorphic among MTBC clinical strains, with SNPs and more frequently in-frame indels occurring in the PGRS domain of the protein and resulting in the gain/loss of one or more Gly-Gly-Ala/X repeats (Talarico et al, 2005, 2007; Wang et al, 2011; McEvoy et al, 2012). These findings provided an experimental support to the possible involvement of PE_PGRS33, as well as other PE_PGRS proteins, in the antigenic variability of Mtb (Talarico et al, 2005, 2007).…”

“…Nevertheless, a recent study questioned this hypothesis in favor of the evolutionary conservation of the pe_pgrs33 gene as indicated by the surprisingly low dN/dS ratio calculated taking into account 95 MTBC clinical strains (Copin et al, 2014). To date, pe_pgrs33 alleles showing frameshift or large in-frame indels have been associated with non-cavitary pulmonary TB or extrapulmonary TB in children (Talarico et al, 2007; Wang et al, 2011), though the actual implications of these genetic variations on the pathogenesis and virulence of Mtb have not yet been explored.…”