The Acinetobacter baumannii Mla system and glycerophospholipid transport to the outer membrane
Cassandra Kamischke,
Junping Fan,
Julien Bergeron,
Hemantha D Kulasekara,
Zachary D Dalebroux,
Anika Burrell,
Justin M Kollman,
Samuel I Miller
Affiliations
Cassandra Kamischke
Department of Microbiology, University of Washington, Seattle, United States
Junping Fan
Department of Microbiology, University of Washington, Seattle, United States
Julien Bergeron
Department of Biochemistry, University of Washington, Seattle, United States; Department of Molecular Biology and Biotechnology, The University of Sheffield, Sheffield, United Kingdom
Hemantha D Kulasekara
Department of Microbiology, University of Washington, Seattle, United States
Zachary D Dalebroux
Department of Microbiology, University of Washington, Seattle, United States
Anika Burrell
Department of Biochemistry, University of Washington, Seattle, United States
Justin M Kollman
Department of Biochemistry, University of Washington, Seattle, United States
Department of Microbiology, University of Washington, Seattle, United States; Department of Genome Sciences, University of Washington, Seattle, United States; Department of Medicine, University of Washington, Seattle, United States
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.
