1. Microbiology and Infectious Disease
Download icon

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

  1. Cassandra Kamischke
  2. Junping Fan
  3. Julien Bergeron
  4. Hemantha D Kulasekara
  5. Zachary D Dalebroux
  6. Anika Burrell
  7. Justin M Kollman
  8. Samuel I Miller  Is a corresponding author
  1. University of Washington, United States
Research Article
  • Cited 22
  • Views 2,946
  • Annotations
Cite this article as: eLife 2019;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.

Article and author information

Author details

  1. Cassandra Kamischke

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Junping Fan

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Julien Bergeron

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Hemantha D Kulasekara

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Zachary D Dalebroux

    Department of Microbiology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Anika Burrell

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  7. Justin M Kollman

    Department of Biochemistry, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.

  8. Samuel I Miller

    Department of Microbiology, University of Washington, Seattle, United States
    For correspondence
    millersi@uw.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1638-2181

Funding

National Institute of Allergy and Infectious Diseases (U19AI107775)

  • Samuel I Miller

National Institutes of Health (R01GM118396)

  • Justin M Kollman

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Tâm Mignot, Aix Marseille University-CNRS UMR7283, France

Publication history

  1. Received: July 17, 2018
  2. Accepted: January 11, 2019
  3. Accepted Manuscript published: January 14, 2019 (version 1)
  4. Version of Record published: February 6, 2019 (version 2)

Copyright

© 2019, Kamischke et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 2,946
    Page views
  • 475
    Downloads
  • 22
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Categories and tags

Further reading

    1. Epidemiology and Global Health
    2. Microbiology and Infectious Disease

    Intestinal microbiology shapes population health impacts of diet and lifestyle risk exposures in Torres Strait Islander communities

    Fredrick M Mobegi et al.
    Research Article

    Poor diet and lifestyle exposures are implicated in substantial global increases in non-communicable disease burden in low-income, remote, and Indigenous communities. This observational study investigated the contribution of the fecal microbiome to influence host physiology in two Indigenous communities in the Torres Strait Islands: Mer, a remote island where a traditional diet predominates, and Waiben a more accessible island with greater access to takeaway food and alcohol. Counterintuitively, disease markers were more pronounced in Mer residents. However, island-specific differences in disease risk were explained, in part, by microbiome traits. The absence of Alistipes onderdonkii, for example, significantly (p=0.014) moderated island-specific patterns of systolic blood pressure in multivariate-adjusted models. We also report mediatory relationships between traits of the fecal metagenome, disease markers, and risk exposures. Understanding how intestinal microbiome traits influence response to disease risk exposures is critical for the development of strategies that mitigate the growing burden of cardiometabolic disease in these communities.

    1. Immunology and Inflammation
    2. Microbiology and Infectious Disease

    NAIP-NLRC4-deficient mice are susceptible to shigellosis

    Patrick S Mitchell et al.
    Research Article

    Bacteria of the genus Shigella cause shigellosis, a severe gastrointestinal disease that is a major cause of diarrhea-associated mortality in humans. Mice are highly resistant to Shigella and the lack of a tractable physiological model of shigellosis has impeded our understanding of this important human disease. Here we propose that the differential susceptibility of mice and humans to Shigella is due to mouse-specific activation of the NAIP–NLRC4 inflammasome. We find that NAIP–NLRC4-deficient mice are highly susceptible to oral Shigella infection and recapitulate the clinical features of human shigellosis. Although inflammasomes are generally thought to promote Shigella pathogenesis, we instead demonstrate that intestinal epithelial cell (IEC)-specific NAIP–NLRC4 activity is sufficient to protect mice from shigellosis. In addition to describing a new mouse model of shigellosis, our results suggest that the lack of an inflammasome response in IECs may help explain the susceptibility of humans to shigellosis.

    1. Microbiology and Infectious Disease

    Unbiased homeologous recombination during pneumococcal transformation allows for multiple chromosomal integration events

    Jun Kurushima et al.
    Research Article Updated

    The spread of antimicrobial resistance and vaccine escape in the human pathogen Streptococcus pneumoniae can be largely attributed to competence-induced transformation. Here, we studied this process at the single-cell level. We show that within isogenic populations, all cells become naturally competent and bind exogenous DNA. We find that transformation is highly efficient and that the chromosomal location of the integration site or whether the transformed gene is encoded on the leading or lagging strand has limited influence on recombination efficiency. Indeed, we have observed multiple recombination events in single recipients in real-time. However, because of saturation and because a single-stranded donor DNA replaces the original allele, transformation efficiency has an upper threshold of approximately 50% of the population. The fixed mechanism of transformation results in a fail-safe strategy for the population as half of the population generally keeps an intact copy of the original genome.