The Acinetobacter baumannii Mla system and glycerophospholipid transport to the outer membrane

Elife. 2019 Jan 14:8:e40171. doi: 10.7554/eLife.40171.

Abstract

The outer membrane (OM) of Gram-negative bacteria serves as a selective permeability barrier that allows entry of essential nutrients while excluding toxic compounds, including antibiotics. The OM is asymmetric and contains an outer leaflet of lipopolysaccharides (LPS) or lipooligosaccharides (LOS) and an inner leaflet of glycerophospholipids (GPL). We screened Acinetobacter baumannii transposon mutants and identified a number of mutants with OM defects, including an ABC transporter system homologous to the Mla system in E. coli. We further show that this opportunistic, antibiotic-resistant pathogen uses this multicomponent protein complex and ATP hydrolysis at the inner membrane to promote GPL export to the OM. The broad conservation of the Mla system in Gram-negative bacteria suggests the system may play a conserved role in OM biogenesis. The importance of the Mla system to Acinetobacter baumannii OM integrity and antibiotic sensitivity suggests that its components may serve as new antimicrobial therapeutic targets.

Keywords: ABC Transporter; Acinetobacter baumannii; glycerophospholipids; infectious disease; microbiology.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acinetobacter baumannii / genetics
  • Acinetobacter baumannii / metabolism*
  • Adenosine Triphosphate / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Outer Membrane Proteins / metabolism*
  • Biological Transport
  • Cell Membrane / metabolism*
  • Computational Biology
  • Cryoelectron Microscopy
  • DNA Transposable Elements
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / metabolism
  • Genome, Bacterial
  • Glycerophospholipids / metabolism*
  • Hydrolysis
  • Lipopolysaccharides / metabolism*
  • Molecular Conformation
  • Mutagenesis
  • Mutation
  • Phenotype

Substances

  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • DNA Transposable Elements
  • Escherichia coli Proteins
  • Glycerophospholipids
  • Lipopolysaccharides
  • lipid-linked oligosaccharides
  • Adenosine Triphosphate