English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Analysis of mutations in pncA reveals non-overlapping patterns among various lineages of Mycobacterium tuberculosis

Baddam, R., Kumar, N., Wieler, L. H., Lankapalli, A. K., Ahmed, N., Peacock, S. J., et al. (2018). Analysis of mutations in pncA reveals non-overlapping patterns among various lineages of Mycobacterium tuberculosis. Scientific Reports, 8(1): 4628. doi:10.1038/s41598-018-22883-9.

Item is

Basic

show hide
Genre: Journal Article

Files

show Files
hide Files
:
shh976.pdf (Publisher version), 3MB
Name:
shh976.pdf
Description:
OA
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
:
shh976b.pdf (Any fulltext), 669KB
Name:
shh976b.pdf
Description:
Erratum. - (Artikelnummer: 7892)
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-

Locators

show

Creators

show
hide
 Creators:
Baddam, Ramani, Author
Kumar, Narender, Author
Wieler, Lothar H., Author
Lankapalli, Aditya Kumar1, Author              
Ahmed, Niyaz, Author
Peacock, Sharon J., Author
Semmler, Torsten, Author
Affiliations:
1Archaeogenetics, Max Planck Institute for the Science of Human History, Max Planck Society, ou_2074310              

Content

show
hide
Free keywords: -
 Abstract: Pyrazinamide (PZA) is an important first-line anti-tuberculosis drug, resistance to which occurs primarily due to mutations in pncA (Rv2043c) that encodes the pyrazinamidase enzyme responsible for conversion of pro-drug PZA into its active form. Previous studies have reported numerous resistance-conferring mutations distributed across the entire length of pncA without any hotspot regions. As different lineages of Mycobacterium tuberculosis display a strong geographic association, we sought to understand whether the genetic background influenced the distribution of mutations in pncA. We analyzed the whole genome sequence data of 1,480 clinical isolates representing four major M. tuberculosis lineages to identify the distribution of mutations in the complete operon (Rv2044c-pncA-Rv2042c) and its upstream promoter region. We observed a non-overlapping pattern of mutations among various lineages and identified a lineage 3-specific frame-shift deletion in gene Rv2044c upstream of pncA that disrupted the stop codon and led to its fusion with pncA. This resulted in the addition of a novel domain of unknown function (DUF2784) to the pyrazinamidase enzyme. The variant molecule was computationally modelled and physico-chemical parameters determined to ascertain stability. Although the functional impact of this mutation remains unknown, its lineage specific nature highlights the importance of genetic background and warrants further study.

Details

show
hide
Language(s): eng - English
 Dates: 2018-03-15
 Publication Status: Published online
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: Other: shh976
DOI: 10.1038/s41598-018-22883-9
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Scientific Reports
  Abbreviation : Sci. Rep.
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: London, UK : Nature Publishing Group
Pages: 4628 Volume / Issue: 8 (1) Sequence Number: 4628 Start / End Page: - Identifier: ISSN: 2045-2322
CoNE: https://pure.mpg.de/cone/journals/resource/2045-2322