The plasmid-mediated evolution of the mycobacterial ESX (Type VII) secretion systems
Open accessAbstract
BACKGROUND: The genome of Mycobacterium tuberculosis contains five copies of the ESX gene cluster, each encoding a dedicated protein secretion system. These ESX secretion systems have been defined as a novel Type VII secretion machinery, responsible for the secretion of proteins across the characteristic outer mycomembrane of the mycobacteria. Some of these secretion systems are involved in virulence and survival in M. tuberculosis; however they are also present in other non-pathogenic mycobacteria, and have been identified in some non-mycobacterial actinomycetes. Three components of the ESX gene cluster have also been found clustered in some gram positive monoderm organisms and are predicted to have preceded the ESX gene cluster. RESULTS: This study used in silico and phylogenetic analyses to describe the evolution of the ESX gene cluster from the WXG-FtsK cluster of monoderm bacteria to the five ESX clusters present in M. tuberculosis and other slow-growing mycobacteria. The ancestral gene cluster, ESX-4, was identified in several nonmycomembrane producing actinobacteria as well as the mycomembrane-containing Corynebacteriales in which the ESX cluster began to evolve and diversify. A novel ESX gene cluster, ESX-4EVOL, was identified in some non-mycobacterial actinomycetes and M. abscessus subsp. bolletii. ESX-4EVOL contains all of the conserved components of the ESX gene cluster and appears to be a precursor of the mycobacterial ESX duplications. Between two and seven ESX gene clusters were identified in each mycobacterial species, with ESX-2 and ESX-5 specifically associated with the slow growers. The order of ESX duplication in the mycobacteria is redefined as ESX-4, ESX-3, ESX-1 and then ESX-2 and ESX-5. Plasmid-encoded precursor ESX gene clusters were identified for each of the genomic ESX-3, -1, -2 and -5 gene clusters, suggesting a novel plasmid-mediated mechanism of ESX duplication and evolution. CONCLUSIONS: The influence of the various ESX gene clusters on vital biological and virulence-related functions has clearly influenced the diversification and success of the various mycobacterial species, and their evolution from the non-pathogenic fast-growing saprophytic to the slow-growing pathogenic organisms.
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ESX/T7S systems are encoded in different sections of the mycobacterial chromosome and seem to have evolved by gene duplication and diversification from simpler systems shuffled around in actinobacterial and mycobacterial species, often mediated by plasmids encoding ESX/T7S elements and type IV secretion elements.
“These systems, encoded in different sections of the mycobacterial chromosome, seem to have evolved by gene duplication and diversification from simpler systems that were shuffled around in different actinobacterial and mycobacterial species, often mediated by plasmids encoding ESX/T7S elements as well as elements of type IV secretion systems (21)(22)(23).”
From ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins (2019) · cites this paper as [22]
ESX-4, ESX-3, and ESX-1 are present in most fast-growing and slow-growing mycobacteria, while ESX-2 and ESX-5 are found only in selected slow-growing mycobacteria and represent the most recently evolved systems.
“While ESX-4, ESX-3, and ESX-1 are present in most fast-growing and slowgrowing mycobacteria, ESX-2 and ESX-5 systems are found only in selected slow-growing mycobacteria and thus represent the most recently evolved systems (21,22).”
From ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins (2019) · cites this paper as [22]
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- Authors
- Newton-Foot, M., Warren, R. M., Sampson, S. L., van Helden, P. D., & Gey van Pittius, N. C.
- Affiliations
- South African Medical Research Council (ZA)
- Corresponding author
- Newton-Foot, Mae
- Venue
- BMC Evolutionary Biology
- Published
- 2016-03-15
- Volume
- 16
- Issue
- 1
- Pages
- 62-62
- ISSN
- 1471-2148 (ISSN-L)
- PMC
- PMC4791881
- OpenAlex
- W2300801912
- Cited by
- 75
- References
- 50
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 6 · 2023: 7 · 2022: 9 · 2021: 8 · 2020: 9 · 2019: 10 · 2018: 4 · 2017: 8 · 2016: 3
- FWCI
- 7.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- BMC Evolutionary Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- SUNScholar (Stellenbosch University) (submittedVersion)
- 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
- ESX secretion system, type VII secretion system, Mycobacterium tuberculosis, mycomembrane, slow-growing mycobacteria, actinomycetes, Mycobacterium abscessus subsp. bolletii, Corynebacteriales, virulence, phylogenetic analysis
- MeSH terms
- Type VII Secretion Systems, Bacteria, Bacterial Proteins, Multigene Family, Mycobacterium, Mycobacterium tuberculosis, Phylogeny, Plasmids, Protein Transport
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