Lipid a remodeling is a pathoadaptive mechanism that impacts lipopolysaccharide recognition and intracellular survival of Burkholderia pseudomallei

Michael H. Norris, Nawarat Somprasong, Herbert P. Schweizer, Apichai Tuanyok

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Burkholderia pseudomallei causes the severe disease melioidosis. The bacterium subverts the host immune system and replicates inside cells, and host mortality results primarily from sepsis-related complications. Lipopolysaccharide (LPS) is a major virulence factor and mediator of sepsis that many pathogens capable of intracellular growth modify to reduce their immunological "footprint." The binding strength of B. pseudomallei LPS for human LPS binding protein (hLBP) was measured using surface plasmon resonance. The structures of lipid A isolated from B. pseudomallei under different temperatures were analyzed by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), and the gene expression of two lipid A remodeling genes, lpxO and pagL, was investigated. The LPS was characterized for its ability to trigger tumor necrosis factor alpha (TNF-α) release and to activate caspase-11-triggered pyroptosis by introduction of LPS into the cytosol. Lipid A from long-term chronic-infection isolates was isolated and characterized by MALDI-TOF MS and also by the ability to trigger caspase-11-mediated cell death. Lipid A from B. pseudomallei 1026b lpxO and pagL mutants were characterized by positive- And negative-mode MALDI-TOF MS to ultimately identify their role in lipid A structural modifications. Replication of lpxO and pagL mutants and their complements within macrophages showed that lipid A remodeling can effect growth in host cells and activation of caspase-11-mediated cytotoxicity.

Original languageEnglish (US)
Article numbere00360-18
JournalInfection and Immunity
Volume86
Issue number10
DOIs
StatePublished - Oct 1 2018
Externally publishedYes

Keywords

  • Burkholderia pseudomallei
  • Inflammasome
  • Intracellular pathogen
  • Lipid A
  • Lipopolysaccharide

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Infectious Diseases

Fingerprint

Dive into the research topics of 'Lipid a remodeling is a pathoadaptive mechanism that impacts lipopolysaccharide recognition and intracellular survival of Burkholderia pseudomallei'. Together they form a unique fingerprint.

Cite this