Three-dimensional low shear culture of Mycobacterium bovis BCG induces biofilm formation and antimicrobial drug tolerance
Abstract Mycobacteria naturally grow as corded biofilms in liquid media without detergent. Such detergent-free biofilm phenotypes may reflect the growth pattern of bacilli in tuberculous lung lesions. New strategies are required to treat tuberculosis, which is responsible for more deaths each year t...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-02-01
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| Series: | npj Biofilms and Microbiomes |
| Online Access: | https://doi.org/10.1038/s41522-021-00186-8 |
| _version_ | 1818420583619100672 |
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| author | Daire Cantillon Justyna Wroblewska Ian Cooper Melanie J. Newport Simon J. Waddell |
| author_facet | Daire Cantillon Justyna Wroblewska Ian Cooper Melanie J. Newport Simon J. Waddell |
| author_sort | Daire Cantillon |
| collection | DOAJ |
| description | Abstract Mycobacteria naturally grow as corded biofilms in liquid media without detergent. Such detergent-free biofilm phenotypes may reflect the growth pattern of bacilli in tuberculous lung lesions. New strategies are required to treat tuberculosis, which is responsible for more deaths each year than any other bacterial disease. The lengthy 6-month regimen for drug-sensitive tuberculosis is necessary to remove antimicrobial drug tolerant populations of bacilli that persist through drug therapy. The role of biofilm-like growth in the generation of these sub-populations remains poorly understood despite the hypothesised clinical significance and mounting evidence of biofilms in pathogenesis. We adapt a three-dimensional Rotary Cell Culture System to model M. bovis BCG biofilm growth in low-shear detergent-free liquid suspension. Importantly, biofilms form without attachment to artificial surfaces and without severe nutrient starvation or environmental stress. Biofilm-derived planktonic bacilli are tolerant to isoniazid and streptomycin, but not rifampicin. This phenotypic drug tolerance is lost after passage in drug-free media. Transcriptional profiling reveals induction of cell surface regulators, sigE and BCG_0559c alongside the ESX-5 secretion apparatus in these low-shear liquid-suspension biofilms. This study engineers and characterises mycobacteria grown as a suspended biofilm, illuminating new drug discovery pathways for this deadly disease. |
| first_indexed | 2024-12-14T12:56:47Z |
| format | Article |
| id | doaj.art-e7819f1bcebf4e7a86cd42bb30477b29 |
| institution | Directory Open Access Journal |
| issn | 2055-5008 |
| language | English |
| last_indexed | 2024-12-14T12:56:47Z |
| publishDate | 2021-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biofilms and Microbiomes |
| spelling | doaj.art-e7819f1bcebf4e7a86cd42bb30477b292022-12-21T23:00:33ZengNature Portfolionpj Biofilms and Microbiomes2055-50082021-02-01711810.1038/s41522-021-00186-8Three-dimensional low shear culture of Mycobacterium bovis BCG induces biofilm formation and antimicrobial drug toleranceDaire Cantillon0Justyna Wroblewska1Ian Cooper2Melanie J. Newport3Simon J. Waddell4Global Health and Infection, Brighton and Sussex Medical School, University of SussexGlobal Health and Infection, Brighton and Sussex Medical School, University of SussexSchool of Pharmacy & Biomolecular Sciences, University of BrightonGlobal Health and Infection, Brighton and Sussex Medical School, University of SussexGlobal Health and Infection, Brighton and Sussex Medical School, University of SussexAbstract Mycobacteria naturally grow as corded biofilms in liquid media without detergent. Such detergent-free biofilm phenotypes may reflect the growth pattern of bacilli in tuberculous lung lesions. New strategies are required to treat tuberculosis, which is responsible for more deaths each year than any other bacterial disease. The lengthy 6-month regimen for drug-sensitive tuberculosis is necessary to remove antimicrobial drug tolerant populations of bacilli that persist through drug therapy. The role of biofilm-like growth in the generation of these sub-populations remains poorly understood despite the hypothesised clinical significance and mounting evidence of biofilms in pathogenesis. We adapt a three-dimensional Rotary Cell Culture System to model M. bovis BCG biofilm growth in low-shear detergent-free liquid suspension. Importantly, biofilms form without attachment to artificial surfaces and without severe nutrient starvation or environmental stress. Biofilm-derived planktonic bacilli are tolerant to isoniazid and streptomycin, but not rifampicin. This phenotypic drug tolerance is lost after passage in drug-free media. Transcriptional profiling reveals induction of cell surface regulators, sigE and BCG_0559c alongside the ESX-5 secretion apparatus in these low-shear liquid-suspension biofilms. This study engineers and characterises mycobacteria grown as a suspended biofilm, illuminating new drug discovery pathways for this deadly disease.https://doi.org/10.1038/s41522-021-00186-8 |
| spellingShingle | Daire Cantillon Justyna Wroblewska Ian Cooper Melanie J. Newport Simon J. Waddell Three-dimensional low shear culture of Mycobacterium bovis BCG induces biofilm formation and antimicrobial drug tolerance npj Biofilms and Microbiomes |
| title | Three-dimensional low shear culture of Mycobacterium bovis BCG induces biofilm formation and antimicrobial drug tolerance |
| title_full | Three-dimensional low shear culture of Mycobacterium bovis BCG induces biofilm formation and antimicrobial drug tolerance |
| title_fullStr | Three-dimensional low shear culture of Mycobacterium bovis BCG induces biofilm formation and antimicrobial drug tolerance |
| title_full_unstemmed | Three-dimensional low shear culture of Mycobacterium bovis BCG induces biofilm formation and antimicrobial drug tolerance |
| title_short | Three-dimensional low shear culture of Mycobacterium bovis BCG induces biofilm formation and antimicrobial drug tolerance |
| title_sort | three dimensional low shear culture of mycobacterium bovis bcg induces biofilm formation and antimicrobial drug tolerance |
| url | https://doi.org/10.1038/s41522-021-00186-8 |
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