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The role of antibiotic-derived mycobacterial vesicles in tuberculosis pathogenesis

Davids, C. J. LU ; Umashankar-Rao, K. LU ; Kassaliete, J. LU ; Ahmadi, S. LU ; Happonen, L. LU ; Welinder, C. LU ; Tullberg, C. LU ; Grey, C. LU orcid ; Puthia, M. LU and Godaly, Gabriela LU orcid (2024) In Scientific Reports 14. p.1-16
Abstract

Pulmonary tuberculosis (TB) causes progressive and irreversible damage to lung tissue, a damage that may not fully resolve after treatment. Mycobacterial vesicles (MVs), which are poorly understood, may contribute to TB pathology. This study investigated the effects of stress, such as treatment with conventional TB antibiotics rifampicin, isoniazid, ethambutol, or treatment with an antimycobacterial peptide (NZX), on mycobacterial vesiculation. Stress from minimal inhibitory concentrations of antibiotics, or peptide all increased MV formation. Electron microscopy and lipid profiling revealed that these vesicles, about 40 nm in size, were released from the bacterial inner membrane and consisted of apolar lipids. Using mass spectrometry,... (More)

Pulmonary tuberculosis (TB) causes progressive and irreversible damage to lung tissue, a damage that may not fully resolve after treatment. Mycobacterial vesicles (MVs), which are poorly understood, may contribute to TB pathology. This study investigated the effects of stress, such as treatment with conventional TB antibiotics rifampicin, isoniazid, ethambutol, or treatment with an antimycobacterial peptide (NZX), on mycobacterial vesiculation. Stress from minimal inhibitory concentrations of antibiotics, or peptide all increased MV formation. Electron microscopy and lipid profiling revealed that these vesicles, about 40 nm in size, were released from the bacterial inner membrane and consisted of apolar lipids. Using mass spectrometry, the study identified key differences in MVs protein cargo dependent on the antibiotic used, especially with ethambutol-induced MVs that contained proteins from several mycobacterial pathways. Additionally, toxicology analysis using different concentrations of MVs on primary human macrophages and the monocytic cells indicated that MVs from the different treatments were not toxic to human cells, however induced specific inflammatory profiles. In conclusion, this study identified mycobacterial vesicles to be a potential contributor to tuberculosis pathology.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
14
article number
28198
pages
1 - 16
publisher
Nature Publishing Group
external identifiers
  • pmid:39548211
  • scopus:85209090528
ISSN
2045-2322
DOI
10.1038/s41598-024-79215-3
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2024.
id
3849351f-aadf-4167-9157-563443814b02
date added to LUP
2024-12-04 05:25:41
date last changed
2025-07-02 22:52:39
@article{3849351f-aadf-4167-9157-563443814b02,
  abstract     = {{<p>Pulmonary tuberculosis (TB) causes progressive and irreversible damage to lung tissue, a damage that may not fully resolve after treatment. Mycobacterial vesicles (MVs), which are poorly understood, may contribute to TB pathology. This study investigated the effects of stress, such as treatment with conventional TB antibiotics rifampicin, isoniazid, ethambutol, or treatment with an antimycobacterial peptide (NZX), on mycobacterial vesiculation. Stress from minimal inhibitory concentrations of antibiotics, or peptide all increased MV formation. Electron microscopy and lipid profiling revealed that these vesicles, about 40 nm in size, were released from the bacterial inner membrane and consisted of apolar lipids. Using mass spectrometry, the study identified key differences in MVs protein cargo dependent on the antibiotic used, especially with ethambutol-induced MVs that contained proteins from several mycobacterial pathways. Additionally, toxicology analysis using different concentrations of MVs on primary human macrophages and the monocytic cells indicated that MVs from the different treatments were not toxic to human cells, however induced specific inflammatory profiles. In conclusion, this study identified mycobacterial vesicles to be a potential contributor to tuberculosis pathology.</p>}},
  author       = {{Davids, C. J. and Umashankar-Rao, K. and Kassaliete, J. and Ahmadi, S. and Happonen, L. and Welinder, C. and Tullberg, C. and Grey, C. and Puthia, M. and Godaly, Gabriela}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  pages        = {{1--16}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{The role of antibiotic-derived mycobacterial vesicles in tuberculosis pathogenesis}},
  url          = {{http://dx.doi.org/10.1038/s41598-024-79215-3}},
  doi          = {{10.1038/s41598-024-79215-3}},
  volume       = {{14}},
  year         = {{2024}},
}