Global assessment of genomic regions required for growth in Mycobacterium tuberculosis

Identifying genomic elements required for viability is central to our understanding of the basic physiology of bacterial pathogens. Recently, the combination of high-density mutagenesis and deep sequencing has allowed for the identification of required and conditionally required genes in many bacter...

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Bibliographic Details
Published in:PLoS pathogens 2012-09, Vol.8 (9), p.e1002946
Main Authors: Zhang, Yanjia J, Ioerger, Thomas R, Huttenhower, Curtis, Long, Jarukit E, Sassetti, Christopher M, Sacchettini, James C, Rubin, Eric J
Format: Article
Language:English
Subjects:
Bacterial genetics
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Base Sequence
Biology
Chromosomes
Gene Expression Profiling
Genes
Genetic aspects
Genetics
Genome
Genome, Bacterial
Genomes
Genomics
Growth
Health aspects
High-Throughput Nucleotide Sequencing
Mutagenesis
Mycobacterium tuberculosis
Mycobacterium tuberculosis - genetics
Mycobacterium tuberculosis - growth & development
Mycobacterium tuberculosis - metabolism
Physiological aspects
Proteins
Regulatory Sequences, Nucleic Acid
RNA, Untranslated - genetics
Sequence Analysis, DNA
Virulence (Microbiology)
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Summary:Identifying genomic elements required for viability is central to our understanding of the basic physiology of bacterial pathogens. Recently, the combination of high-density mutagenesis and deep sequencing has allowed for the identification of required and conditionally required genes in many bacteria. Genes, however, make up only a part of the complex genomes of important bacterial pathogens. Here, we use an unbiased analysis to comprehensively identify genomic regions, including genes, domains, and intergenic elements, required for the optimal growth of Mycobacterium tuberculosis, a major global health pathogen. We found that several proteins jointly contain both domains required for optimal growth and domains that are dispensable. In addition, many non-coding regions, including regulatory elements and non-coding RNAs, are critical for mycobacterial growth. Our analysis shows that the genetic requirements for growth are more complex than can be appreciated using gene-centric analysis.
ISSN:1553-7374
1553-7366
1553-7374
DOI:10.1371/journal.ppat.1002946