Characterization of DNA methylation in Malawian <i>Mycobacterium tuberculosis</i> clinical isolates



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-.

Access the full-text of this item by clicking on the Open Access link.

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
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