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...

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Autores principales:	Daire Cantillon, Justyna Wroblewska, Ian Cooper, Melanie J. Newport, Simon J. Waddell
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Microbial ecology QR100-130
Acceso en línea:	https://doaj.org/article/e7819f1bcebf4e7a86cd42bb30477b29
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spelling	oai:doaj.org-article:e7819f1bcebf4e7a86cd42bb30477b292021-12-02T10:44:23ZThree-dimensional low shear culture of Mycobacterium bovis BCG induces biofilm formation and antimicrobial drug tolerance10.1038/s41522-021-00186-82055-5008https://doaj.org/article/e7819f1bcebf4e7a86cd42bb30477b292021-02-01T00:00:00Zhttps://doi.org/10.1038/s41522-021-00186-8https://doaj.org/toc/2055-5008Abstract 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.Daire CantillonJustyna WroblewskaIan CooperMelanie J. NewportSimon J. WaddellNature PortfolioarticleMicrobial ecologyQR100-130ENnpj Biofilms and Microbiomes, Vol 7, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbial ecology QR100-130
spellingShingle	Microbial ecology QR100-130 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
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.
format	article
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
title	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_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_sort	three-dimensional low shear culture of mycobacterium bovis bcg induces biofilm formation and antimicrobial drug tolerance
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/e7819f1bcebf4e7a86cd42bb30477b29
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Three-dimensional low shear culture of Mycobacterium bovis BCG induces biofilm formation and antimicrobial drug tolerance

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