A non‐RD1 gene cluster is required for Snm secretion in Mycobacterium tuberculosis
Abstract
Summary: The Snm secretion system is a crucial virulence determinant of Mycobacterium tuberculosis . Genes encoding all known components of this alternative secretion pathway are clustered at the same genetic locus, known as RD1. Here, we show that a mutant M. tuberculosis strain containing a transposon insertion in the Rv3615c gene, which is situated outside the RD1 locus, results in loss of Snm secretion. Complementation analysis revealed that both Rv3615c and the downstream gene Rv3614c are required for Snm secretion. Thus, we have renamed the two genes snm9 and snm10 respectively. The snm9::Tn mutant phenocopies bona fide snm mutants, exhibiting attenuation in mice, macrophage growth defects and failure to suppress cytokine induction. Furthermore, yeast two‐hybrid analysis revealed a physical interaction between Snm10 and Snm7 (Rv3882c), suggesting that Snm10 may function in complex with other Snm proteins during secretion. Thus, snm9 and snm10 are the first genes located outside the RD1 locus identified as critical components of Snm secretion. These data indicate that Snm secretion consists of an elaborate network of interactions that likely arose from multiple duplication events during the evolution of M. tuberculosis .
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Different proteins, such as EspA, EspC, EspD, and EccA1, may be essential to contributing to secretion and stabilizing the core ESX/T7S complex in the case of ESX-1.
“Moreover, different proteins, such as EspA, EspC, EspD, and EccA1, may be essential to contributing to secretion and stabilizing the core ESX/T7S complex in the case of ESX-1 (44)(45)(46)(47).”
From ESX/Type VII Secretion Systems—An Important Way Out for Mycobacterial Proteins (2019) · cites this paper as [45]
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- Authors
- MacGurn, J. A., Raghavan, S., Stanley, S. A., & Cox, J. S.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Cox, Jeffery S.
- Venue
- Molecular Microbiology
- Publisher
- Wiley
- Published
- 2005-08-19
- Volume
- 57
- Issue
- 6
- Pages
- 1653-1663
- ISSN
- 0950-382X (ISSN-L)
- 1365-2958
- OpenAlex
- W1506741363
- Cited by
- 186
- References
- 29
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 8 · 2021: 6 · 2020: 11 · 2019: 5 · 2018: 7 · 2017: 10 · 2016: 8 · 2015: 6 · 2014: 13 · 2013: 12 · 2012: 15
- FWCI
- 6.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Microbiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases (AI 68540)
- 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, virulence, transposon mutants, complementation, macrophage proliferation, cytokine induction, protein-protein interaction, gene duplication, bacterial virulence genes
- MeSH terms
- Amino Acid Sequence, Animals, Antigens, Bacterial, Bacterial Proteins, Genes, Bacterial, Multigene Family, Genetic Complementation Test, Humans, Macrophages, Mice, Inbred C57BL, Molecular Sequence Data, Mycobacterium tuberculosis, Gene Expression Regulation, Bacterial, Culture Media, Conditioned, Two-Hybrid System Techniques, Mice
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