Comparison of proline-glutamate-proline-glutamate-polymorphic GC-rich sequences family protein Wag22 (Rv1759c), PE_PGRS31 (Rv1768), PE_PGRS32 (Rv1803), and PE_PGRS33 gene (Rv1818c) in exponential state and under In vitro model of latency in same clinical isolates of Mycobacterium tuberculosis: Frameshift mutation in extensively drug-resistant and totally drug-resistant tuberculosis bacilli
| Title: | Comparison of proline-glutamate-proline-glutamate-polymorphic GC-rich sequences family protein Wag22 (Rv1759c), PE_PGRS31 (Rv1768), PE_PGRS32 (Rv1803), and PE_PGRS33 gene (Rv1818c) in exponential state and under In vitro model of latency in same clinical isolates of Mycobacterium tuberculosis: Frameshift mutation in extensively drug-resistant and totally drug-resistant tuberculosis bacilli |
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| Authors: | Parissa Farnia, Poopak Farnia, Jalaledin Ghanavi, Saeid Besharati, Ali Akbar Velayati |
| Source: | Biomedical and Biotechnology Research Journal, Vol 7, Iss 4, Pp 621-632 (2023) |
| Publisher Information: | Wolters Kluwer Medknow Publications, 2023. |
| Publication Year: | 2023 |
| Collection: | LCC:Biotechnology |
| Subject Terms: | extensively drug-resistant tuberculosis, latency, totally drug-resistant–tuberculosis, pe_pgrs31, pe_pgrs32 and pe_pgrs33 gene, proline-glutamate-polymorphic gc-rich sequences family protein, rv1759c, Biotechnology, TP248.13-248.65 |
| More Details: | Background: Proline-glutamate (PE)/proline-PE (PPE) proteins play an important role in the development of mycobacterial pathogenicity by modulating the host immune system. In the present investigation, the structural changes in PE-polymorphic GC-rich sequences (PGRS) family protein Wag22 (Rv1759c), PE_PGRS31 (Rv1768), PE_PGRS32 (Rv1803), and PE_PGRS33 gene (Rv1818c) were compared and analyzed in exponential state and under in vitro model of latency in same clinical isolates of Mycobacterium tuberculosis (MTB). Methods: MTB strains were isolated from clinically and laboratory-confirmed cases of tuberculosis (TB). The TB isolates were subjected to the Xpert MTB/rifampin test and then, further susceptibility testing using proportional methods was performed on them. The isolates were characterized using both 16S–23S RNA and hsp65 genes spacer polymerase chain reaction-restriction fragment length polymorphism. Selected isolates studied at two experimental set–up at exponential phase OD 600 = 0.05 (5 cfu/mL × 106 cfu/mL) and under zero oxygen and nutrition for 26 months to selected isolates studied at two experimental setup in exponential phase OD600 = 0.05 (5 cfu/mL × 106 cfu/mL) and under zero oxygen and nutrition after 26 months. Whole-genome sequencing was performed on studied isolates and the protein structures were analyzed using a bioinformatics web server. Results: No deletion, insertion, or substation occurred in susceptible, mono-drug and multidrug resistant-TB isolates were observed at PE-PGRS family protein Wag22 (Rv1759c) and PE_PGRS31 (Rv1768) at exponential phase. Although, a large deletion (at Rv1759c; Rv1768) was observed in extensively drug-resistant (XDR) and totally drug-resistant (TDR) TB isolates at the exponential phase. All studied TDR-TB isolates had a common deletion position from amino acid 1 (methionine) to amino acid 83 (glycine) and from amino acid 725 (proline) to amino acid 914 (threonine) at PE-PGRS family protein Wag22 (Rv1759c). At PE_PGRS32 (Rv1803), deletion occurred from amino acid 1 (methionine) to amino acid 212 (glycine) in latent TDR-TB bacilli. No changes in Rv1803 were observed in other studied isolates. In contrast, 66.6% of studied isolates had either insertion, deletion, substitution, or combination of changes at PE_PGRS33 (Rv1818c). However, the majority of changes at Rv1818c occurred in drug-resistant isolates. We also documented the region of deletion and insertion at PE_PGRS33 (Rv1818c) is different in active and latent TDR-TB isolates. Conclusions: Changes in these PE-PGRS family protein was associated with drug susceptibility patterns of individual isolates. Our result showed a total frameshift mutation of protein that had a different length in comparison to the original protein. These changes might disturb the interactions between XDR and TDR-TB isolates and immune responses, which needs further investigation. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2588-9834 2588-9842 |
| Relation: | http://www.bmbtrj.org/article.asp?issn=2588-9834;year=2023;volume=7;issue=4;spage=621;epage=632;aulast=Farnia; https://doaj.org/toc/2588-9834; https://doaj.org/toc/2588-9842 |
| DOI: | 10.4103/bbrj.bbrj_271_23 |
| Access URL: | https://doaj.org/article/4e81e2333c2c48b081d4e9fa35ee81de |
| Accession Number: | edsdoj.4e81e2333c2c48b081d4e9fa35ee81de |
| Database: | Directory of Open Access Journals |
| ISSN: | 25889834 25889842 |
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| DOI: | 10.4103/bbrj.bbrj_271_23 |
| Published in: | Biomedical and Biotechnology Research Journal |
| Language: | English |