1. Growth of Mycobacterium tuberculosis biofilms containing free mycolic acids and harbouring drug-tolerant bacteria.
- Author
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Ojha AK, Baughn AD, Sambandan D, Hsu T, Trivelli X, Guerardel Y, Alahari A, Kremer L, Jacobs WR Jr, and Hatfull GF
- Subjects
- Antitubercular Agents pharmacology, Biofilms drug effects, Carbon Dioxide metabolism, Humans, Iron metabolism, Lipids chemistry, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis metabolism, Mycolic Acids chemistry, Plankton chemistry, Plankton microbiology, Tuberculosis, Pulmonary drug therapy, Zinc metabolism, Biofilms growth & development, Drug Resistance, Bacterial, Mycobacterium tuberculosis drug effects, Mycobacterium tuberculosis physiology, Mycolic Acids metabolism, Tuberculosis, Pulmonary microbiology
- Abstract
Successful treatment of human tuberculosis requires 6-9 months' therapy with multiple antibiotics. Incomplete clearance of tubercle bacilli frequently results in disease relapse, presumably as a result of reactivation of persistent drug-tolerant Mycobacterium tuberculosis cells, although the nature and location of these persisters are not known. In other pathogens, antibiotic tolerance is often associated with the formation of biofilms--organized communities of surface-attached cells--but physiologically and genetically defined M. tuberculosis biofilms have not been described. Here, we show that M. tuberculosis forms biofilms with specific environmental and genetic requirements distinct from those for planktonic growth, which contain an extracellular matrix rich in free mycolic acids, and harbour an important drug-tolerant population that persist despite exposure to high levels of antibiotics.
- Published
- 2008
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