The ESAT-6 gene cluster of Mycobacterium tuberculosis and other high G+C Gram-positive bacteria

Gey van Pittius, Nico C; Gamieldien, Junaid; Hide, Winston; Brown, Gordon D; Siezen, Roland J; Beyers, Albert D

doi:10.1186/gb-2001-2-10-research0044

Cited by 383Tuberculosis Research and EpidemiologyMycobacterium research and diagnosisBacterial Genetics and Biotechnology

The ESAT-6 gene cluster of Mycobacterium tuberculosis and other high G+C Gram-positive bacteria

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Gey van Pittius, Nico C, Gamieldien, Junaid, Hide, Winston, Brown, Gordon D, Siezen, Roland J, Beyers, Albert D·2001·Genome Biology

DOI 10.1186/gb-2001-2-10-research0044PMC PMC57799

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Abstract

BACKGROUND: The genome of Mycobacterium tuberculosis H37Rv has five copies of a cluster of genes known as the ESAT-6 loci. These clusters contain members of the CFP-10 (lhp) and ESAT-6 (esat-6) gene families (encoding secreted T-cell antigens that lack detectable secretion signals) as well as genes encoding secreted, cell-wall-associated subtilisin-like serine proteases, putative ABC transporters, ATP-binding proteins and other membrane-associated proteins. These membrane-associated and energy-providing proteins may function to secrete members of the ESAT-6 and CFP-10 protein families, and the proteases may be involved in processing the secreted peptide. RESULTS: Finished and unfinished genome sequencing data of 98 publicly available microbial genomes has been analyzed for the presence of orthologs of the ESAT-6 loci. The multiple duplicates of the ESAT-6 gene cluster found in the genome of M. tuberculosis H37Rv are also conserved in the genomes of other mycobacteria, for example M. tuberculosis CDC1551, M. tuberculosis 210, M. bovis, M. leprae, M. avium, and the avirulent strain M. smegmatis. Phylogenetic analyses of the resulting sequences have established the duplication order of the gene clusters and demonstrated that the gene cluster known as region 4 (Rv3444c-3450c) is ancestral. Region 4 is also the only region for which an ortholog could be found in the genomes of Corynebacterium diphtheriae and Streptomyces coelicolor. CONCLUSIONS: Comparative genomic analysis revealed that the presence of the ESAT-6 gene cluster is a feature of some high-G+C Gram-positive bacteria. Multiple duplications of this cluster have occurred and are maintained only within the genomes of members of the genus Mycobacterium.

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ESX-4 appears to represent the most ancestral T7S system in mycobacteria.
“ESX-4, which harbors a smaller number of genes than other ESX loci (Table 2), appears to represent the most ancestral T7S system in mycobacteria [12].”
From Systematic Genetic Nomenclature for Type VII Secretion Systems (2009) · cites this paper as [12]

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Authors: Gey van Pittius, N. C., Gamieldien, J., Hide, W., Brown, G. D., Siezen, R. J., & Beyers, A. D.
Affiliations: University of the Western Cape (ZA)
University of Oxford (GB)
Radboud University Nijmegen (NL)
Stellenbosch University (ZA)
ORCID: Gamieldien, Junaid
Brown, Gordon D
Siezen, Roland J
Venue: Genome Biology
Publisher: Springer Science and Business Media LLC
Published: 2001-09-19
Volume: 2
Issue: 10
Pages: RESEARCH0044-RESEARCH0044
ISSN: 1465-6906 (ISSN-L)
1474-760X
DOI: 10.1186/gb-2001-2-10-research0044
PMC: PMC57799
OpenAlex: W1904782847
Cited by: 375
References: 34
Citations by year: 2026: 7 · 2025: 7 · 2024: 9 · 2023: 14 · 2022: 12 · 2021: 15 · 2020: 8 · 2019: 16 · 2018: 14 · 2017: 13 · 2016: 24 · 2015: 15 · 2014: 21 · 2013: 20 · 2012: 26
FWCI: 8.43
Type: journal article
Language: en
Open access: gold
doi.org
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Genome biology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
SUNScholar (Stellenbosch University) (submittedVersion)
Funders: U.S. Department of Agriculture
Topics: Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
Health Sciences › Medicine › Epidemiology › Mycobacterium research and diagnosis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
Keywords: Mycobacterium tuberculosis, CFP-10, ESAT-6, subtilisin-like protease, gene duplication, comparative genomics, orthologs, T cell antigens, mycobacteria, phylogenetic analysis, Corynebacterium diphtheriae, Streptomyces coelicolor
MeSH terms: Antigens, Bacterial, Bacterial Proteins, Corynebacterium diphtheriae, DNA, Bacterial, Multigene Family, Gram-Positive Bacteria, Mycobacterium, Mycobacterium avium, Mycobacterium bovis, Mycobacterium leprae, Mycobacterium tuberculosis, Phylogeny, Streptomyces, Genome, Bacterial, Mycobacterium avium subsp. paratuberculosis, Sequence Analysis, DNA, Mycobacterium smegmatis, GC Rich Sequence

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The ESAT-6 gene cluster of Mycobacterium tuberculosis and other high G+C Gram-positive bacteria

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