The Mycobacterium tuberculosis MmpL11 cell wall lipid transporter is important for biofilm formation, intracellular growth, and nonreplicating persistence

Catherine C. Wright, Fong Fu Hsu, Eusondia Arnett, Jennifer L. Dunaj, Patrick M. Davidson, Sophia A. Pacheco, Melanie Harriff, David Lewinsohn, Larry S. Schlesinger, Georgiana Purdy

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The mycobacterial cell wall is crucial to the host-pathogen interface, because it provides a barrier against antibiotics and the host immune response. In addition, cell wall lipids are mycobacterial virulence factors. The mycobacterial membrane protein large (MmpL) proteins are cell wall lipid transporters that are important for basic mycobacterial physiology and Mycobacterium tuberculosis pathogenesis. MmpL3 and MmpL11 are conserved across pathogenic and nonpathogenic mycobacteria, a feature consistent with an important role in the basic physiology of the bacterium. MmpL3 is essential and transports trehalose monomycolate to the mycobacterial surface. In this report, we characterize the role of MmpL11 in M. tuberculosis. M. tuberculosis mmpL11 mutants have altered biofilms associated with lower levels of mycolic acid wax ester and long-chain triacylglycerols than those for wild-type bacteria. While the growth rate of the mmpL11 mutant is similar to that of wild-type M. tuberculosis in macrophages, the mutant exhibits impaired survival in an in vitro granuloma model. Finally, we show that the survival or recovery of the mmpL11 mutant is impaired when it is incubated under conditions of nutrient and oxygen starvation. Our results suggest that MmpL11 and its cell wall lipid substrates are important for survival in the context of adaptive immune pressure and for nonreplicating persistence, both of which are critically important aspects of M. tuberculosis pathogenicity.

Original languageEnglish (US)
Article number00131-17
JournalInfection and Immunity
Volume85
Issue number8
DOIs
StatePublished - Aug 1 2017

Fingerprint

Biofilms
Mycobacterium tuberculosis
Cell Wall
Lipids
Growth
Mycolic Acids
Bacteria
Waxes
Virulence Factors
Mycobacterium
Starvation
Granuloma
Virulence
Membrane Proteins
Esters
Triglycerides
Macrophages
Oxygen
Anti-Bacterial Agents
Pressure

Keywords

  • Biofilm
  • Cell wall
  • Granuloma
  • Lipid transport
  • Lipid transporter
  • MmpL11
  • Mycobacterium tuberculosis
  • Nonreplicating persistence
  • Tuberculosis

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Cite this

The Mycobacterium tuberculosis MmpL11 cell wall lipid transporter is important for biofilm formation, intracellular growth, and nonreplicating persistence. / Wright, Catherine C.; Hsu, Fong Fu; Arnett, Eusondia; Dunaj, Jennifer L.; Davidson, Patrick M.; Pacheco, Sophia A.; Harriff, Melanie; Lewinsohn, David; Schlesinger, Larry S.; Purdy, Georgiana.

In: Infection and Immunity, Vol. 85, No. 8, 00131-17, 01.08.2017.

Research output: Contribution to journalArticle

Wright, Catherine C. ; Hsu, Fong Fu ; Arnett, Eusondia ; Dunaj, Jennifer L. ; Davidson, Patrick M. ; Pacheco, Sophia A. ; Harriff, Melanie ; Lewinsohn, David ; Schlesinger, Larry S. ; Purdy, Georgiana. / The Mycobacterium tuberculosis MmpL11 cell wall lipid transporter is important for biofilm formation, intracellular growth, and nonreplicating persistence. In: Infection and Immunity. 2017 ; Vol. 85, No. 8.
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AU - Davidson, Patrick M.

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