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Uncovering the mechanisms of Acinetobacter baumannii virulence

Nature Reviews Microbiology volume 16, pages 91–102 (2018)Cite this article

Subjects

Key Points

  • Acinetobacter baumannii is an opportunistic human pathogen that predominantly causes health-care-associated infections.

  • Many members of the genus Acinetobacter, including Acinetobacter nosocomialis, Acinetobacter pittii, Acinetobacter dijkshoorniae and Acinetobacter seifertii, are also human pathogens and increasingly identified as the cause of infections.

  • A. baumannii is rapidly developing resistance mechanisms to antibiotics.

  • The ability of A. baumannii to withstand desiccation and to form biofilms promotes its success as a nosocomial pathogen.

  • Fundamental virulence factors, such as surface adhesins, glycoconjugates and secretion systems, directly contribute to the pathogenesis of A. baumannii.

Abstract

Acinetobacter baumannii is a nosocomial pathogen that causes ventilator-associated as well as bloodstream infections in critically ill patients, and the spread of multidrug-resistant Acinetobacter strains is cause for concern. Much of the success of A. baumannii can be directly attributed to its plastic genome, which rapidly mutates when faced with adversity and stress. However, fundamental virulence mechanisms beyond canonical drug resistance were recently uncovered that enable A. baumannii and, to a limited extent, other medically relevant Acinetobacter species to successfully thrive in the health-care environment. In this Review, we explore the molecular features that promote environmental persistence, including desiccation resistance, biofilm formation and motility, and we discuss the most recently identified virulence factors, such as secretion systems, surface glycoconjugates and micronutrient acquisition systems that collectively enable these pathogens to successfully infect their hosts.

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Figure 1: Protein secretion and export in Acinetobacter baumannii.
Figure 2: Acinetobacter baumannii surface-exposed glycoconjugates.
Figure 3: Colistin resistance mechanisms of Acinetobacter baumannii.

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Acknowledgements

During the preparation of this Review article, C.M.H. was funded as a W.M. Keck Postdoctoral Fellow. The efforts of S.W.H. and M.F.F. were funded by a US National Institutes of Health (NIH) grant (1R01AI125363-01).

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Authors and Affiliations

  1. Department of Molecular Microbiology, Washington University School of Medicine in St. Louis, St. Louis, 63110, Missouri, USA

    Christian M. Harding, Seth W. Hennon & Mario F. Feldman

  2. VaxNewMo LLC, St. Louis, 63108, Missouri, USA

    Christian M. Harding & Mario F. Feldman

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  1. Christian M. Harding
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Contributions

C.M.H., S.W.H. and M.F.F. researched data for the article, made substantial contributions to discussions of the content and wrote the article. C.M.H. and M.F.F. also reviewed and/or edited the manuscript before submission.

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Correspondence to Mario F. Feldman.

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The authors declare no competing financial interests.

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Glossary

Lipooligosaccharide

(LOS). A macromolecule consisting of lipid A and a core oligosaccharide found in the outer leaflet of the outer membrane of Gram-negative bacteria. Lipid A is also considered an endotoxin and is the ligand for Toll-like receptor 4.

Catalase

An enzyme that detoxifies hydrogen peroxide into water and oxygen.

Phagocytosis

The process used by many immune cells, including macrophages, to engulf invading bacteria.

Two-component regulatory system

A two-part relay system used by bacteria for sensing and responding to environmental stimuli, consisting of a membrane-bound histidine kinase and a soluble response regulator.

Surface-associated motility

A mechanism of bacterial translocation observed on semisolid surfaces and unique to Acinetobacter spp., which is not dependent on pili.

Twitching motility

A mechanism of bacterial translocation dependent on repetitive rounds of type IV pili extension and retraction broadly used by many bacteria.

Opaque phase variants

A subset of an Acinetobacter baumannii population that has an opaque appearance when viewed under a microscope and differs from the translucent form in terms of both appearance and virulence.

Glycoconjugates

Macromolecules composed of a carbohydrate covalently attached to at least one other lipid or protein molecule.

Lipopolysaccharide

(LPS). A macromolecule consisting of lipid A, a core oligosaccharide and a polysaccharide O antigen found in the outer leaflet of the outer membrane of Gram-negative bacteria.

Complement-mediated killing

A process that is part of the innate immune system consisting of soluble proteins in the blood that coordinately bind to an invading pathogen, triggering either lysis or the recruitment of immune cells to clear the pathogen.

O-glycosylation

The covalent attachment of a carbohydrate moiety to the hydroxyl group of a serine or threonine in a polypeptide.

Siderophores

High-affinity iron-binding molecules secreted by many bacterial pathogens to scavenge iron.

Adhesion

The process whereby bacteria associate with a surface, either a biotic surface (for example, human cells) or an abiotic surface (for example, medical equipment and devices).

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Harding, C., Hennon, S. & Feldman, M. Uncovering the mechanisms of Acinetobacter baumannii virulence. Nat Rev Microbiol 16, 91–102 (2018). https://doi.org/10.1038/nrmicro.2017.148

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