Trehalose-recycling ABC transporter LpqY-SugA-SugB-SugC is essential for virulence of Mycobacterium tuberculosis

Rainer Kalscheuer, Brian Weinrick, Usha Veeraraghavan, Gurdyal S. Besra, William R. Jacobs

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

Mycobacterium tuberculosis (Mtb) is an exclusively human pathogen that proliferates within phagosomes of host phagocytes. Host lipids are believed to provide the major carbon and energy sources for Mtb, with only limited availability of carbohydrates. There is an apparent paradox because five putative carbohydrate uptake permeases are present in Mtb, but there are essentially no host carbohydrates in-side phagosomes. Nevertheless, carbohydrate transporters have been implicated in Mtb pathogenesis, suggesting that acquisition of host sugars is important during some stages of infection. Here we show, however, that the LpqY-SugA-SugB-SugCATP-binding cassette transporter is highly specific for uptake of the disaccharide trehalose, a sugar not present in mammals, thus refuting a role in nutrient acquisition from the host. Trehalose release is known to occur as a byproduct of the biosynthesis of the mycolic acid cell envelope by Mtb'santigen85complex.Theantigen85complexconstitutesagroup of extracellular mycolyl transferases, which transfer the lipid moiety of the glycolipid trehalose monomycolate (TMM) to arabinogalactan or another molecule of TMM, yielding trehalose dimycolate. These reactions also lead to the concomitant extracellular release of the trehalose moiety of TMM. We found that the LpqY-SugA-SugB-SugC ATP-binding cassette transporter is a recycling system mediating the retrograde transport of released trehalose. Perturbations in trehalose recycling strongly impaired virulence of Mtb. This study reveals an unexpected accessory component involved in the formation of the mycolic acid cell envelope in mycobacteria and provides a previously unknown role for sugar transporters in bacterial pathogenesis.

Original languageEnglish (US)
Pages (from-to)21761-21766
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number50
DOIs
StatePublished - Dec 14 2010

Keywords

  • Carbon metabolism
  • Cell wall formation
  • Microbial pathogenesis
  • Mycolic acid biosynthesis

ASJC Scopus subject areas

  • General

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