Functional characterization of the Mycobacterium abscessus genome coupled with condition specific transcriptomics reveals conserved molecular strategies for host adaptation and persistence

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dc.contributor.author Miranda-CasoLuengo, Aleksandra A.
dc.contributor.author Staunton, Patrick M.
dc.contributor.author Dinan, Adam M.
dc.contributor.author Lohan, Amanda J.
dc.contributor.author Loftus, Brendan J.
dc.date.accessioned 2017-06-21T11:01:24Z
dc.date.available 2017-06-21T11:01:24Z
dc.date.issued 2016-08-05
dc.identifier.citation Miranda-CasoLuengo, A. A., Staunton, P. M., Dinan, A. M., Lohan, A. J. and Loftus, B. J. (2016) 'Functional characterization of the Mycobacterium abscessus genome coupled with condition specific transcriptomics reveals conserved molecular strategies for host adaptation and persistence', BMC Genomics, 17, 553 (12pp). doi:10.1186/s12864-016-2868-y en
dc.identifier.volume 17
dc.identifier.startpage 1
dc.identifier.endpage 12
dc.identifier.issn 1471-2164
dc.identifier.uri http://hdl.handle.net/10468/4121
dc.identifier.doi 10.1186/s12864-016-2868-y
dc.description.abstract Background: Mycobacterium abscessus subsp. abscessus (MAB) is a highly drug resistant mycobacterium and the most common respiratory pathogen among the rapidly growing non-tuberculous mycobacteria. MAB is also one of the most deadly of the emerging cystic fibrosis (CF) pathogens requiring prolonged treatment with multiple antibiotics. In addition to its “mycobacterial” virulence genes, the genome of MAB harbours a large accessory genome, presumably acquired via lateral gene transfer including homologs shared with the CF pathogens Pseudomonas aeruginosa and Burkholderia cepacia. While multiple genome sequences are available there is little functional genomics data available for this important pathogen. Results: We report here the first multi-omics approach to characterize the primary transcriptome, coding potential and potential regulatory regions of the MAB genome utilizing differential RNA sequencing (dRNA-seq), RNA-seq, Ribosome profiling and LC-MS proteomics. In addition we attempt to address the genomes contribution to the molecular systems that underlie MAB’s adaptation and persistence in the human host through an examination of MABs transcriptional response to a number of clinically relevant conditions. These include hypoxia, exposure to sub-inhibitory concentrations of antibiotics and growth in an artificial sputum designed to mimic the conditions within the cystic fibrosis lung. Conclusions: Our integrated map provides the first comprehensive view of the primary transcriptome of MAB and evidence for the translation of over one hundred new short open reading frames (sORFs). Our map will act as a resource for ongoing functional genomics characterization of MAB and our transcriptome data from clinically relevant stresses informs our understanding of MAB’s adaptation to life in the CF lung. MAB’s adaptation to growth in artificial CF sputum highlights shared metabolic strategies with other CF pathogens including P. aeruginosa and mirrors the transcriptional responses that lead to persistence in mycobacteria. These strategies include an increased reliance on amino acid metabolism, and fatty acid catabolism and highlights the relevance of the glyoxylate shunt to growth in the CF lung. Our data suggests that, similar to what is seen in chronically persisting P. aeruginosa, progression towards a biofilm mode of growth would play a more prominent role in a longer-term MAB infection. Finally, MAB’s transcriptional response to antibiotics highlights the role of antibiotic modifications enzymes, active transport and the evolutionarily conserved WhiB7 driven antibiotic resistance regulon. en
dc.description.sponsorship Science Foundation Ireland (grants 05/RP1/B908; 05/RP1/908/EC07); Wellcome Trust (grant no. 099817/Z/12/Z). en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher BioMed Central en
dc.relation.uri https://bmcgenomics.biomedcentral.com/articles/10.1186/s12864-016-2868-y
dc.rights © 2016, the Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. en
dc.rights.uri http://creativecommons.org/licenses/by/4.0/ en
dc.subject Integrated map en
dc.subject Mycobacterium abscessus en
dc.subject WhiB7 en
dc.subject Antibiotic en
dc.subject Cystic fibrosis en
dc.title Functional characterization of the Mycobacterium abscessus genome coupled with condition specific transcriptomics reveals conserved molecular strategies for host adaptation and persistence en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Amanda J. Lohan, APC Microbiome Institute, Biosciences Institute, University College Cork, Cork, Ireland +353-21-490-3000 E-mail: amanda.lohan@ucc.ie en
dc.internal.availability Full text available en
dc.description.version Published Version en
dc.contributor.funder Science Foundation Ireland
dc.contributor.funder Wellcome Trust
dc.description.status Peer reviewed en
dc.identifier.journaltitle BMC Genomics en
dc.internal.IRISemailaddress amanda.lohan@ucc.ie en
dc.identifier.articleid 553


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© 2016, the Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Except where otherwise noted, this item's license is described as © 2016, the Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
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