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
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),...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2023-01-01
|
| Series: | Biomedical and Biotechnology Research Journal |
| Subjects: | |
| Online Access: | http://www.bmbtrj.org/article.asp?issn=2588-9834;year=2023;volume=7;issue=4;spage=621;epage=632;aulast=Farnia |
| _version_ | 1797352222564024320 |
|---|---|
| author | Parissa Farnia Poopak Farnia Jalaledin Ghanavi Saeid Besharati Ali Akbar Velayati |
| author_facet | Parissa Farnia Poopak Farnia Jalaledin Ghanavi Saeid Besharati Ali Akbar Velayati |
| author_sort | Parissa Farnia |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T13:13:10Z |
| format | Article |
| id | doaj.art-4e81e2333c2c48b081d4e9fa35ee81de |
| institution | Directory Open Access Journal |
| issn | 2588-9834 2588-9842 |
| language | English |
| last_indexed | 2024-03-08T13:13:10Z |
| publishDate | 2023-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Biomedical and Biotechnology Research Journal |
| spelling | doaj.art-4e81e2333c2c48b081d4e9fa35ee81de2024-01-18T11:02:45ZengWolters Kluwer Medknow PublicationsBiomedical and Biotechnology Research Journal2588-98342588-98422023-01-017462163210.4103/bbrj.bbrj_271_23Comparison 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 bacilliParissa FarniaPoopak FarniaJalaledin GhanaviSaeid BesharatiAli Akbar VelayatiBackground: 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.http://www.bmbtrj.org/article.asp?issn=2588-9834;year=2023;volume=7;issue=4;spage=621;epage=632;aulast=Farniaextensively drug-resistant tuberculosislatencytotally drug-resistant–tuberculosispe_pgrs31pe_pgrs32 and pe_pgrs33 geneproline-glutamate-polymorphic gc-rich sequences family proteinrv1759c |
| spellingShingle | Parissa Farnia Poopak Farnia Jalaledin Ghanavi Saeid Besharati Ali Akbar Velayati 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 Biomedical and Biotechnology Research Journal 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 |
| 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 |
| title_full | 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_fullStr | 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_full_unstemmed | 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_short | 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_sort | 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 |
| topic | 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 |
| url | http://www.bmbtrj.org/article.asp?issn=2588-9834;year=2023;volume=7;issue=4;spage=621;epage=632;aulast=Farnia |
| work_keys_str_mv | AT parissafarnia comparisonofprolineglutamateprolineglutamatepolymorphicgcrichsequencesfamilyproteinwag22rv1759cpepgrs31rv1768pepgrs32rv1803andpepgrs33generv1818cinexponentialstateandunderinvitromodeloflatencyinsameclinicalisolatesofmycobacteriumtuberculosisframeshiftmuta AT poopakfarnia comparisonofprolineglutamateprolineglutamatepolymorphicgcrichsequencesfamilyproteinwag22rv1759cpepgrs31rv1768pepgrs32rv1803andpepgrs33generv1818cinexponentialstateandunderinvitromodeloflatencyinsameclinicalisolatesofmycobacteriumtuberculosisframeshiftmuta AT jalaledinghanavi comparisonofprolineglutamateprolineglutamatepolymorphicgcrichsequencesfamilyproteinwag22rv1759cpepgrs31rv1768pepgrs32rv1803andpepgrs33generv1818cinexponentialstateandunderinvitromodeloflatencyinsameclinicalisolatesofmycobacteriumtuberculosisframeshiftmuta AT saeidbesharati comparisonofprolineglutamateprolineglutamatepolymorphicgcrichsequencesfamilyproteinwag22rv1759cpepgrs31rv1768pepgrs32rv1803andpepgrs33generv1818cinexponentialstateandunderinvitromodeloflatencyinsameclinicalisolatesofmycobacteriumtuberculosisframeshiftmuta AT aliakbarvelayati comparisonofprolineglutamateprolineglutamatepolymorphicgcrichsequencesfamilyproteinwag22rv1759cpepgrs31rv1768pepgrs32rv1803andpepgrs33generv1818cinexponentialstateandunderinvitromodeloflatencyinsameclinicalisolatesofmycobacteriumtuberculosisframeshiftmuta |