Insight into the PZA resistance whole genome of Mycobacterium tuberculosis isolates from Khyber Pakhtunkhwa, Pakistan
Abstract Background Tuberculosis (TB) is a global public health issue, getting worse due to emergence of resistance. Pyrazinamide (PZA) is first-line antimicrobial drugs used against non-replicated Mycobacterium tuberculosis (MTB). Data is scarce about whole genome sequencing of PZA resistance (PZA-R) in Khyber Pakhtunkhwa (KP) province of high burden country, Pakistan. In the current study we aimed to find the most common mutations in PZA-R MTB isolates in association with other candidate genes in a whole genome sequence (WGS). Samples were collected from TB suspects and drug susceptibility testing (DST) was performed according according to the WHO standards. The resistant samples were subjected for whole genome sequencing (WGS). The sequence data was through MTBseq and Total Genotyping Solution for Mycobacterium tuberculosis (TGS-TB). Metabolic model was analyzed, using RAST server. Results Among the three whole genome sequences, (NCBI BioProject Accession: PRJNA629298, PRJNA629388) 1997, 1162, and 2053 mutations including indel, was detected. Diverse variability has been detected in the membrane proteins PE and PPE, modulating the host immune response. Nine mutations in coding and promotor region have been detected in pncA with one novel (T-4C) variants. Mutations in the other drug candidate genes, KatG, rpoB have also been detected. Conclusion The metabolic model shows a distinct property. Diversity of variants has been detected in majority of MTB essential genes, functions from cell growth to cell signaling. The current study provides useful information, associated with geographic specific strains for biomarkers development and better management of drug resistance isolates..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2020 |
|---|---|
| Erschienen: |
2020 |
| Enthalten in: |
ResearchSquare.com - (2020) vom: 03. Sept. Zur Gesamtaufnahme - year:2020 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Khan, Muhammad Tahir [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| doi: |
10.21203/rs.3.rs-29899/v1 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XRA033652651 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XRA033652651 | ||
| 003 | DE-627 | ||
| 005 | 20230429203118.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 220113s2020 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.21203/rs.3.rs-29899/v1 |2 doi | |
| 035 | |a (DE-627)XRA033652651 | ||
| 035 | |a (ResearchSquare)10.21203/rs.3.rs-29899/v1 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 082 | 0 | |a 570 |q DE-84 | |
| 100 | 1 | |a Khan, Muhammad Tahir |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Insight into the PZA resistance whole genome of Mycobacterium tuberculosis isolates from Khyber Pakhtunkhwa, Pakistan |
| 264 | 1 | |c 2020 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a Abstract Background Tuberculosis (TB) is a global public health issue, getting worse due to emergence of resistance. Pyrazinamide (PZA) is first-line antimicrobial drugs used against non-replicated Mycobacterium tuberculosis (MTB). Data is scarce about whole genome sequencing of PZA resistance (PZA-R) in Khyber Pakhtunkhwa (KP) province of high burden country, Pakistan. In the current study we aimed to find the most common mutations in PZA-R MTB isolates in association with other candidate genes in a whole genome sequence (WGS). Samples were collected from TB suspects and drug susceptibility testing (DST) was performed according according to the WHO standards. The resistant samples were subjected for whole genome sequencing (WGS). The sequence data was through MTBseq and Total Genotyping Solution for Mycobacterium tuberculosis (TGS-TB). Metabolic model was analyzed, using RAST server. Results Among the three whole genome sequences, (NCBI BioProject Accession: PRJNA629298, PRJNA629388) 1997, 1162, and 2053 mutations including indel, was detected. Diverse variability has been detected in the membrane proteins PE and PPE, modulating the host immune response. Nine mutations in coding and promotor region have been detected in pncA with one novel (T-4C) variants. Mutations in the other drug candidate genes, KatG, rpoB have also been detected. Conclusion The metabolic model shows a distinct property. Diversity of variants has been detected in majority of MTB essential genes, functions from cell growth to cell signaling. The current study provides useful information, associated with geographic specific strains for biomarkers development and better management of drug resistance isolates. | ||
| 700 | 1 | |a Ali, Sajid |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, anwar Sheed |e verfasserin |4 aut | |
| 700 | 1 | |a Ali, Arif |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Abbas |e verfasserin |4 aut | |
| 700 | 1 | |a Kaushak, Aman Chandra |e verfasserin |4 aut | |
| 700 | 1 | |a Irfan, Muhammad |e verfasserin |4 aut | |
| 700 | 1 | |a Chinnasamy, Satheshkumar |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Shulin |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yu-Juan |e verfasserin |4 aut | |
| 700 | 1 | |a Cui, Zhelie |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Amie |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yanjie |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Mingzhu |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Kejia |e verfasserin |4 aut | |
| 700 | 1 | |a Zeb, Muhammad Tariq |e verfasserin |4 aut | |
| 700 | 1 | |a wang, Heng |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Dong Qing |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t ResearchSquare.com |g (2020) vom: 03. Sept. |
| 773 | 1 | 8 | |g year:2020 |g day:03 |g month:09 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.21203/rs.3.rs-29899/v1 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XRA | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |j 2020 |b 03 |c 09 | ||
| 953 | |2 045F |a 570 | ||