Three-dimensional low shear culture of Mycobacterium bovis BCG induces biofilm formation and antimicrobial drug tolerance
| Autor: | Simon J. Waddell, Ian Cooper, Justyna Wroblewska, Daire Cantillon, Melanie J. Newport |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Bacilli Tuberculosis Virulence Factors 030106 microbiology Antitubercular Agents Sigma Factor Applied Microbiology and Biotechnology Microbiology Article Microbial ecology 03 medical and health sciences Bacterial Proteins Drug tolerance Drug Resistance Bacterial Isoniazid medicine Bacteriological Techniques Mycobacterium bovis Bacterial disease biology Antimicrobials Gene Expression Profiling QR100-130 Biological techniques Biofilm Bacteriology Gene Expression Regulation Bacterial biochemical phenomena metabolism and nutrition Antimicrobial medicine.disease biology.organism_classification Culture Media Phenotype 030104 developmental biology Biofilms Streptomycin Pathogens Rifampin Biotechnology medicine.drug |
| Zdroj: | NPJ Biofilms and Microbiomes npj Biofilms and Microbiomes, Vol 7, Iss 1, Pp 1-8 (2021) |
| ISSN: | 2055-5008 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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