s41522-021-00186-8.pdf (1.81 MB)
Three-dimensional low shear culture of Mycobacterium bovis BCG induces biofilm formation and antimicrobial drug tolerance
journal contribution
posted on 2023-06-09, 22:51 authored by Daire Cantillon, Justyna Wroblewska, Ian Cooper, Melanie NewportMelanie Newport, Simon WaddellSimon WaddellMycobacteria 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.
History
Publication status
- Published
File Version
- Published version
Journal
npj Biofilms and MicrobiomesISSN
2055-5008Publisher
Nature ResearchExternal DOI
Volume
7Page range
1-8Article number
a12Department affiliated with
- Global Health and Infection Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-01-22First Open Access (FOA) Date
2021-02-02First Compliant Deposit (FCD) Date
2021-01-22Usage metrics
Categories
No categories selectedKeywords
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC