Miranda-CasoLuengo et al. 2016 (PRJNA295556)

General Details

Title An integrated approach combining RNA-seq, Ribo-seq and Proteomics identifies the coding potential of Mycobacterium abscessus
Organism
Number of Samples 6
Release Date 2015/09/14 00:00
Sequencing Types
Protocol Details

Study Links

Repository Details

SRA SRP063670
ENA SRP063670
GEO GSE72996
BioProject PRJNA295556

Publication

Title
Authors Miranda-CasoLuengo AA,Staunton PM,Dinan AM,Lohan AJ,Loftus BJ
Journal BMC genomics
Publication Date 2016 Aug 5
Abstract 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. 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. 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.
PMC PMC4974804
PMID 27495169
DOI
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)
SRR2392989 PRJNA295556 Mycobacteroides abscessus Ribo-Seq
SRR2392990 PRJNA295556 Mycobacteroides abscessus Ribo-Seq
SRR2392991 PRJNA295556 Mycobacteroides abscessus RNA-Seq
SRR2392992 PRJNA295556 Mycobacteroides abscessus RNA-Seq
SRR2392995 PRJNA295556 Mycobacteroides abscessus CAGE-Seq
SRR2392996 PRJNA295556 Mycobacteroides abscessus CAGE-Seq
Run Accession Study Accession Scientific Name Cell Line Library Type Treatment GWIPS-viz Trips-Viz Reads BAM BigWig (F) BigWig (R)

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