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Genes required for mycobacterial growth defined by high density mutagenesis
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Summary: Despite over a century of research, tuberculosis remains a leading cause of infectious death worldwide. Faced with increasing rates of drug resistance, the identification of genes that are required for the growth of this organism should provide new targets for the design of antimycobacterial agents. Here, we describe the use of transposon site hybridization (TraSH) to comprehensively identify the genes required by the causative agent, Mycobacterium tuberculosis , for optimal growth. These genes include those that can be assigned to essential pathways as well as many of unknown function. The genes important for the growth of M. tuberculosis are largely conserved in the degenerate genome of the leprosy bacillus, Mycobacterium leprae , indicating that non‐essential functions have been selectively lost since this bacterium diverged from other mycobacteria. In contrast, a surprisingly high proportion of these genes lack identifiable orthologues in other bacteria, suggesting that the minimal gene set required for survival varies greatly between organisms with different evolutionary histories.
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“While space does not allow a detailed discussion, loss of glycosylation in plants, fungi or prokaryotes can also lead to cell death.”
From Biological roles of glycans (2017) · cites this paper as [435]
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“The F1Fo-ATP synthase in M. tuberculosis and M. smegmatis has been shown to be essential for optimal growth (29, 103).”
From Energetics of Respiration and Oxidative Phosphorylation in Mycobacteria (2014) · cites this paper as [29]
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Metadata
- Authors
- Sassetti, C. M., Boyd, D. H., & Rubin, E. J.
- Affiliations
- Harvard University (US)
- Corresponding author
- Rubin, Eric J.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2003-03-25
- Volume
- 48
- Issue
- 1
- Pages
- 77-84
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W2128482141
- Cited by
- 2,544
- References
- 25
- Citations by year
- 2026: 43 · 2025: 71 · 2024: 99 · 2023: 77 · 2022: 87 · 2021: 94 · 2020: 114 · 2019: 137 · 2018: 111 · 2017: 129 · 2016: 129 · 2015: 154 · 2014: 149 · 2013: 154 · 2012: 128
- FWCI
- 45.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Damon Runyon Cancer Research Foundation
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI 48704, R01AI048704, R01AI051929, AI51929)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
- Keywords
- Mycobacterium tuberculosis, Mycobacterium leprae, essential genes, bacterial growth, gene essentiality, drug resistance, gene loss, minimal gene set, orthologs
- MeSH terms
- DNA Transposable Elements, Genes, Bacterial, Mycobacterium leprae, Mycobacterium tuberculosis, Mutagenesis, Evolution, Molecular
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