Snapshot of Mycobacterium tuberculosis Phylogenetics from an Indian State of Arunachal Pradesh Bordering China
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Setting and Sample Collection
2.2. Decontamination of Samples and Bactec MGIT 960 Culture Inoculation
2.3. Identification of Cultures Using In-House Multiplex PCR
2.4. Bactec MGIT 960 SIRE DST
2.5. Second Line DST Using Bactec MGIT 960
2.6. Whole Genome Sequencing
2.7. Identification of SNPs
2.8. Assignment of Principal Genetic Groups
2.9. Identification of Lineages and Sub-Lineages Using WGS SNP Barcoding
2.10. Phylogenetic Analysis and Construction of cgMLST
2.11. Data Analysis
3. Results
3.1. Demographic Details and Characteristics of MDR-TB Patients
3.2. Bactec MGIT 960 Culture Results and Identification M. tuberculosis Complex Isolates
3.3. Bactec MGIT 960 SIRE DST
3.4. Bactec MGIT 960 Second Line DST
3.5. Mutations in Genes Associated with First- and Second-Line Drugs Using WGS
3.6. Phylogenetic Analysis and Identification of Lineages Based on cgMLST and SNP Barcoding
3.7. Phylogenetic Analysis Based on PrincipalGenetic Group (PGG)
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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SIRE Drug Susceptibility Pattern by MGIT 960 | Second Line Drug Susceptibility Pattern by MGIT 960 | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
STR | INH | RIF | EMB | n | % | AMK | MFX | LFX | LNZ | n | % |
R | R | R | R | 37 | 29.6% | S | R | R | S | 13 | 35.1% |
R | R | R | S | 2 | 5.4% | ||||||
S | R | S | S | 2 | 5.4% | ||||||
S | S | S | S | 20 | 54.1% | ||||||
S | R | R | S | 15 | 12.0% | S | R | R | S | 2 | 13.3% |
S | S | S | S | 13 | 86.7% | ||||||
S | R | R | R | 5 | 4.0% | S | R | R | S | 2 | 40.0% |
S | S | S | S | 3 | 60.0% | ||||||
R | R | R | S | 9 | 7.2% | S | R | R | S | 1 | 11.1% |
S | S | S | S | 8 | 88.9% | ||||||
S | S | R | S | 3 | 2.4% | S | S | S | S | 3 | 100.% |
S | R | S | S | 8 | 6.4% | − | − | − | − | − | − |
S | S | R | R | 1 | 0.8% | S | S | S | S | 1 | 100% |
R | S | R | S | 1 | 0.8% | S | S | S | S | 1 | 100% |
R | R | S | R | 2 | 1.6% | − | − | − | − | − | − |
R | S | S | S | 1 | 0.8% | − | − | − | − | − | − |
S | S | S | R | 2 | 1.6% | − | − | − | − | − | − |
R | R | S | S | 1 | 0.8% | − | − | − | − | − | − |
S | S | S | S | 40 | 32.0% | − | − | − | − | − | − |
STRS = 74 STRR = 51 | INHS = 48 INHR = 77 | RIFS = 54 RIFR = 71 | EMBs = 78 EMBR = 47 | n = 125 | AMKS = 69 AMKR =2 | MFXS = 49 MFXR = 22 | LFXS =51 LFXR = 20 | LNZS = 71 | n = 71 |
Drug | Gene | Phenotypic DST | Whole Genome Sequencing Results | |||||
---|---|---|---|---|---|---|---|---|
MGIT Result | Mutation | No of Isolates | Lineages | |||||
Lin1 | Lin2 | Lin3 | Lin4 | |||||
RIF (n = 41) | rpoB | R | Ser531Leu | 21/41 (51.2%) | 4 (19%) | 15 (71.4) | 2) | − |
R | Leu511Pro Phe505Leu * | 3/41 (7.3%) | − | 3 (100%) | − | − | ||
R | Leu511Pro His526Gln | 1/41 (2.4%) | − | 1 (100%) | − | − | ||
R | Leu511Pro His526Gln Phe505Leu * | 2/41 (4.9%) | − | 2 (100%) | − | − | ||
R | Asp516Val | 2/41 (4.9%) | − | 1 (50%) | − | − (50%) | ||
R | Asp516Tyr | 1/41 (2.4%) | − | 1 (100%) | − | − | ||
R | His526Tyr | 3 /41(7.3%) | 1 (33.3%) | 2 (66.7%) | − | − | ||
R | His526Asp | 3/41 (7.3%) | - | 3 (100%) | − | − | ||
R | Gln513Pro | 1/41 (2.4%) | − | − | 1 (100%) | |||
rpoB rpoC | R | Ser531Leu Ile561Val * Ile572Thr | 1/41 (2.4%) | − | 1 (100%) | − | − | |
rpoB rpoA | R | Ser531Leu Gly112Ser | 1/41 (2.4%) | 1 (100%) | − | − | − | |
rpoB rpoA | R | Ser531Leu Gly319Lys | 1/41 (2.4%) | − | 1 (100%) | − | − | |
rpoB rpoA | R | Ser531Leu Val264Gly | 1/41 (2.4%) | − | − | − | 1 (100%) | |
rpoB | S | Leu545Met * | 1/41 (2.4%) | − | 1 (100%) | − | − | |
INH (n = 45) | KatG | R | Ser315Thr | 35/45 (77.8%) | 3 (8.6%) | 27 (77.1%) | 3 (8.6%) | 2 (5.8%) |
R | Ser450Leu | 1/45 (2.2%) | 1 (100%) | − | − | − | ||
inhA | R | Ser94Ala | 2/45 (4.4%) | 2 (100%) | − | − | − | |
ahp | R | 52C>T | 2/45 (4.4%) | 2 (100%) | − | − | − | |
Fab | R | 15C>T | 1/45 (2.2%) | 1 (100%) | − | − | ||
Kat Fab | R | Ser140Gly 15C>T | 1/45 (2.2%) | 1 (100%) | − | − | ||
R | Ser315Thr 17C>T | 1/45 (2.2%) | 1 (100%) | − | − | |||
R | Ser315Thr 15C>T | 2/45 (4.4%) | 2 (100%) | − | − | |||
EMB (n = 30) | embB | R | Met306Val | 18/30 (60.0%) | − | 16 (88.8%) | − | 2 (12.2%) |
R | Gly406Asp | 1/30 (3.3%) | − | − | 1 (100%) | − | ||
R | Met306Ile | 4/30 (13.3%) | 1 (25%) | 3 (75%) | − | |||
R | Asp354Ala | 1/30 (3.3%) | − | 1 (100%) | − | − | ||
R | Met306Leu | 1/30 (3.3%) | − | − | 1 (100%) | − | ||
embB | R | Glu405Asp | 1/30 (3.3%) | − | 1 (100%) | − | − | |
R | Gln853ProMet306Val | 2/30 (6.7%) | − | 2 (100%) | − | − | ||
embA embA | R | Met306Val 12C>T | 2/30 (6.7%) | − | 2 (100%) | − | − | |
STR (n = 26) | rpsL | R | Lys43Arg | 22/26 (84.6%) | − | 21 (95.4%) | 1 (19.1%) | − |
R | Lys88Arg | 2/26 (7.7%) | − | 2 (100%) | − | − | ||
rrs | R | 514 A>C | 2/26 (7.7%) | − | 2 (100%) | − | − | |
FQ (n = 16) | gyrA | R | Asp94Gly | 6/16 (37.5%) | − | 5 (83.3%) | 1 (16.6%) | − |
R | Asp94Tyr | 2/16 (12.5%) | − | 2 (100%) | − | − | ||
R | Asp94Asn | 2/16 (12.5%) | − | 2 (100%) | − | − | ||
R | Asp94Ala | 1/16 (6.3%) | − | 1 (100%) | − | − | ||
R | Ala90Val | 1/16 (6.3%) | − | − | − | − (100%) | ||
R | Asp94His | 1/16 (6.3%) | − | 1 (100%) | − | − | ||
gyrB | R | Ile486Leu | 1/16 (6.3%) | − | 1 (100%) | − | − | |
R | Asp461His | 1/16 (6.3%) | − | − | − | 1 (100%) | ||
R | Ala504Val | 1/16 (6.3%) | − | − | − | − | ||
PZA (n = 10) | pncA | R | Asp49Ala | 5/10 (50.0%) | − | 5 (100%) | − | − |
R | Gly108Arg | 2/10 (20.0%) | − | 2 (100%) | − | − | ||
R | 11A>G | 2/10 (20.0%) | − | 2 (100%) | − | − | ||
R | Asp136Tyr | 1/10 (10.0%) | 1 (100%) | − | − | − | ||
AMK (n = 2) | rrs | R | 1484 G>T | 1/2 (50.0%) | − | 1 (100%) | − | − |
R | 1401 A>G | 1/2 (50.0%) | − | 1 (100%) | − | − | ||
ETH (n = 8) | inha | NA | Ser94Ala | 2/8 (25.0%) | 2 (100%) | − | − | − |
fab | NA | 15C>T | 3/8 (37.5%) | − | 3 (100%) | − | − | |
NA | 17G>T | 1/8 (12.5%) | − | − | − | 1 (100%) | ||
ethA | NA | 886_886del | 2/8(25.0%) | − | 1 (50%) | − | 1 (50%) | |
Cysr (n = 2) | alr | NA | Met343Thr | 2/2 (100.0%) | − | 2 (100%) | − | − |
PAS (n = 2) | thy | NA | 16C>T | 1/2 (50.0%) | − | 1 (100%) | − | − |
folC | NA | Ile43Thr | 1/2 (50.0%) | − | 1 (100%) | − | − |
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Mudliar, S.k.R.; Kulsum, U.; Rufai, S.B.; Umpo, M.; Nyori, M.; Singh, S. Snapshot of Mycobacterium tuberculosis Phylogenetics from an Indian State of Arunachal Pradesh Bordering China. Genes 2022, 13, 263. https://doi.org/10.3390/genes13020263
Mudliar SkR, Kulsum U, Rufai SB, Umpo M, Nyori M, Singh S. Snapshot of Mycobacterium tuberculosis Phylogenetics from an Indian State of Arunachal Pradesh Bordering China. Genes. 2022; 13(2):263. https://doi.org/10.3390/genes13020263
Chicago/Turabian StyleMudliar, Shiv kumar Rashmi, Umay Kulsum, Syed Beenish Rufai, Mika Umpo, Moi Nyori, and Sarman Singh. 2022. "Snapshot of Mycobacterium tuberculosis Phylogenetics from an Indian State of Arunachal Pradesh Bordering China" Genes 13, no. 2: 263. https://doi.org/10.3390/genes13020263
APA StyleMudliar, S. k. R., Kulsum, U., Rufai, S. B., Umpo, M., Nyori, M., & Singh, S. (2022). Snapshot of Mycobacterium tuberculosis Phylogenetics from an Indian State of Arunachal Pradesh Bordering China. Genes, 13(2), 263. https://doi.org/10.3390/genes13020263