Lineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated <named-content content-type="genus-species">Escherichia coli</named-content> ST131 Clone

ABSTRACT Escherichia coli sequence type 131 (ST131) is a clone of uropathogenic E. coli that has emerged rapidly and disseminated globally in both clinical and community settings. Members of the ST131 lineage from across the globe have been comprehensively characterized in terms of antibiotic resist...

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Autores principales:	Brian M. Forde, Minh-Duy Phan, Jayde A. Gawthorne, Melinda M. Ashcroft, Mitchell Stanton-Cook, Sohinee Sarkar, Kate M. Peters, Kok-Gan Chan, Teik Min Chong, Wai-Fong Yin, Mathew Upton, Mark A. Schembri, Scott A. Beatson
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8f5d6f2700cd452d95ad3a83e5c92829
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spelling	oai:doaj.org-article:8f5d6f2700cd452d95ad3a83e5c928292021-11-15T15:41:24ZLineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated <named-content content-type="genus-species">Escherichia coli</named-content> ST131 Clone10.1128/mBio.01602-152150-7511https://doaj.org/article/8f5d6f2700cd452d95ad3a83e5c928292015-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01602-15https://doaj.org/toc/2150-7511ABSTRACT Escherichia coli sequence type 131 (ST131) is a clone of uropathogenic E. coli that has emerged rapidly and disseminated globally in both clinical and community settings. Members of the ST131 lineage from across the globe have been comprehensively characterized in terms of antibiotic resistance, virulence potential, and pathogenicity, but to date nothing is known about the methylome of these important human pathogens. Here we used single-molecule real-time (SMRT) PacBio sequencing to determine the methylome of E. coli EC958, the most-well-characterized completely sequenced ST131 strain. Our analysis of 52,081 methylated adenines in the genome of EC958 discovered three m6A methylation motifs that have not been described previously. Subsequent SMRT sequencing of isogenic knockout mutants identified the two type I methyltransferases (MTases) and one type IIG MTase responsible for m6A methylation of novel recognition sites. Although both type I sites were rare, the type IIG sites accounted for more than 12% of all methylated adenines in EC958. Analysis of the distribution of MTase genes across 95 ST131 genomes revealed their prevalence is highly conserved within the ST131 lineage, with most variation due to the presence or absence of mobile genetic elements on which individual MTase genes are located. IMPORTANCE DNA modification plays a crucial role in bacterial regulation. Despite several examples demonstrating the role of methyltransferase (MTase) enzymes in bacterial virulence, investigation of this phenomenon on a whole-genome scale has remained elusive until now. Here we used single-molecule real-time (SMRT) sequencing to determine the first complete methylome of a strain from the multidrug-resistant E. coli sequence type 131 (ST131) lineage. By interrogating the methylome computationally and with further SMRT sequencing of isogenic mutants representing previously uncharacterized MTase genes, we defined the target sequences of three novel ST131-specific MTases and determined the genomic distribution of all MTase target sequences. Using a large collection of 95 previously sequenced ST131 genomes, we identified mobile genetic elements as a major factor driving diversity in DNA methylation patterns. Overall, our analysis highlights the potential for DNA methylation to dramatically influence gene regulation at the transcriptional level within a well-defined E. coli clone.Brian M. FordeMinh-Duy PhanJayde A. GawthorneMelinda M. AshcroftMitchell Stanton-CookSohinee SarkarKate M. PetersKok-Gan ChanTeik Min ChongWai-Fong YinMathew UptonMark A. SchembriScott A. BeatsonAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 6 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Brian M. Forde Minh-Duy Phan Jayde A. Gawthorne Melinda M. Ashcroft Mitchell Stanton-Cook Sohinee Sarkar Kate M. Peters Kok-Gan Chan Teik Min Chong Wai-Fong Yin Mathew Upton Mark A. Schembri Scott A. Beatson Lineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated <named-content content-type="genus-species">Escherichia coli</named-content> ST131 Clone
description	ABSTRACT Escherichia coli sequence type 131 (ST131) is a clone of uropathogenic E. coli that has emerged rapidly and disseminated globally in both clinical and community settings. Members of the ST131 lineage from across the globe have been comprehensively characterized in terms of antibiotic resistance, virulence potential, and pathogenicity, but to date nothing is known about the methylome of these important human pathogens. Here we used single-molecule real-time (SMRT) PacBio sequencing to determine the methylome of E. coli EC958, the most-well-characterized completely sequenced ST131 strain. Our analysis of 52,081 methylated adenines in the genome of EC958 discovered three m6A methylation motifs that have not been described previously. Subsequent SMRT sequencing of isogenic knockout mutants identified the two type I methyltransferases (MTases) and one type IIG MTase responsible for m6A methylation of novel recognition sites. Although both type I sites were rare, the type IIG sites accounted for more than 12% of all methylated adenines in EC958. Analysis of the distribution of MTase genes across 95 ST131 genomes revealed their prevalence is highly conserved within the ST131 lineage, with most variation due to the presence or absence of mobile genetic elements on which individual MTase genes are located. IMPORTANCE DNA modification plays a crucial role in bacterial regulation. Despite several examples demonstrating the role of methyltransferase (MTase) enzymes in bacterial virulence, investigation of this phenomenon on a whole-genome scale has remained elusive until now. Here we used single-molecule real-time (SMRT) sequencing to determine the first complete methylome of a strain from the multidrug-resistant E. coli sequence type 131 (ST131) lineage. By interrogating the methylome computationally and with further SMRT sequencing of isogenic mutants representing previously uncharacterized MTase genes, we defined the target sequences of three novel ST131-specific MTases and determined the genomic distribution of all MTase target sequences. Using a large collection of 95 previously sequenced ST131 genomes, we identified mobile genetic elements as a major factor driving diversity in DNA methylation patterns. Overall, our analysis highlights the potential for DNA methylation to dramatically influence gene regulation at the transcriptional level within a well-defined E. coli clone.
format	article
author	Brian M. Forde Minh-Duy Phan Jayde A. Gawthorne Melinda M. Ashcroft Mitchell Stanton-Cook Sohinee Sarkar Kate M. Peters Kok-Gan Chan Teik Min Chong Wai-Fong Yin Mathew Upton Mark A. Schembri Scott A. Beatson
author_facet	Brian M. Forde Minh-Duy Phan Jayde A. Gawthorne Melinda M. Ashcroft Mitchell Stanton-Cook Sohinee Sarkar Kate M. Peters Kok-Gan Chan Teik Min Chong Wai-Fong Yin Mathew Upton Mark A. Schembri Scott A. Beatson
author_sort	Brian M. Forde
title	Lineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated <named-content content-type="genus-species">Escherichia coli</named-content> ST131 Clone
title_short	Lineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated <named-content content-type="genus-species">Escherichia coli</named-content> ST131 Clone
title_full	Lineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated <named-content content-type="genus-species">Escherichia coli</named-content> ST131 Clone
title_fullStr	Lineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated <named-content content-type="genus-species">Escherichia coli</named-content> ST131 Clone
title_full_unstemmed	Lineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated <named-content content-type="genus-species">Escherichia coli</named-content> ST131 Clone
title_sort	lineage-specific methyltransferases define the methylome of the globally disseminated <named-content content-type="genus-species">escherichia coli</named-content> st131 clone
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/8f5d6f2700cd452d95ad3a83e5c92829
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Lineage-Specific Methyltransferases Define the Methylome of the Globally Disseminated <named-content content-type="genus-species">Escherichia coli</named-content> ST131 Clone

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