Ndhlovu, Victor, Kiran, Anmol ORCID: 0000-0003-2680-2303, Sloan, Derek J, Mandala, Wilson, Nliwasa, Marriott, Everett, Dean B, Kumwenda, Benjamin, Mwapasa, Mphatso, Kontogianni, Konstantina, Kamdolozi, Mercy et al (show 3 more authors)
(2020)
Characterization of DNA methylation in Malawian <i>Mycobacterium tuberculosis</i> clinical isolates.
PEERJ, 8.
e10432-.
Abstract
<h4>Background</h4>Although <i>Mycobacterium tuberculosis (Mtb)</i> strains exhibit genomic homology of >99%, there is considerable variation in the phenotype. The underlying mechanisms of phenotypic heterogeneity in <i>Mtb</i> are not well understood but epigenetic variation is thought to contribute. At present the methylome of <i>Mtb</i> has not been completely characterized.<h4>Methods</h4>We completed methylomes of 18 <i>Mycobacterium tuberculosis</i> (<i>Mtb</i>) clinical isolates from Malawi representing the largest number of <i>Mtb</i> genomes to be completed in a single study using Single Molecule Real Time (SMRT) sequencing to date.<h4>Results</h4>We replicate and confirm four methylation disrupting mutations in 4 lineages of <i>Mtb</i>. For the first time we report complete loss of methylation courtesy of C758T (S253L) mutation in the <i>MamB</i> gene of Indo-oceanic lineage of <i>Mtb</i>. Additionally, we report a novel missense mutation G454A (G152S) in the <i>MamA</i> gene of the Euro-American lineage which could potentially be attributed to total disruption of methylation in the CCC<b>A</b>G motif but partial loss in a partner motif. Through a genomic and methylome comparative analysis with a global sample of sixteen, we report previously unknown mutations affecting the <i>pks15/1</i> locus in L6 isolates. We confirm that methylation in <i>Mtb</i> is lineage specific although some unresolved issues still remain.
Item Type: | Article |
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Uncontrolled Keywords: | Mycobacterium tuberculosis, DNA methylation, Single Molecule Real Time Sequencing, Malawian Mtb clinical isolates, Motif |
Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences |
Depositing User: | Symplectic Admin |
Date Deposited: | 17 May 2021 09:24 |
Last Modified: | 10 Oct 2023 14:28 |
DOI: | 10.7717/peerj.10432 |
Open Access URL: | http://doi.org/10.7717/peerj.10432 |
Related URLs: | |
URI: | https://livrepository.liverpool.ac.uk/id/eprint/3123024 |