title: Growth of Mycobacterium tuberculosis biofilms containing free mycolic acids and harbouring drug-tolerant bacteria.
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.
authors.affiliation: Department of Biological Sciences, University of Pittsburgh, Pittsburgh, PA 15260, USA.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Ojha
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Baughn
authors.forename: Dhinakaran
authors.initials: D
authors.lastname: Sambandan
authors.forename: Tsungda
authors.initials: T
authors.lastname: Hsu
authors.forename: Xavier
authors.initials: X
authors.lastname: Trivelli
authors.forename: Yann
authors.initials: Y
authors.lastname: Guerardel
authors.forename: Anuradha
authors.initials: A
authors.lastname: Alahari
authors.forename: Laurent
authors.initials: L
authors.lastname: Kremer
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
authors.forename: Graham F
authors.initials: GF
authors.lastname: Hatfull
mesh_terms: D000995:Antitubercular Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D002245:Carbon Dioxide / Q000378:metabolism; D024881:Drug Resistance, Bacterial; D006801:Humans; D007501:Iron / Q000378:metabolism; D008055:Lipids / Q000737:chemistry; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009171:Mycolic Acids / Q000737:chemistry / Q000378:metabolism*; D010933:Plankton / Q000737:chemistry / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology*; D015032:Zinc / Q000378:metabolism
chemical_list: D000995:Antitubercular Agents; D008055:Lipids; D009171:Mycolic Acids; D002245:Carbon Dioxide; D007501:Iron; D015032:Zinc