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Colony phase variation switch modulates antimicrobial tolerance and biofilm formation in Acinetobacter baumannii
Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine). Institute of Biomedical and Allied Health Sciences, University of Health Sciences, Lahore, Pakistan.
Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).ORCID iD: 0000-0002-1439-6216
Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
Umeå University, Faculty of Medicine, Umeå Centre for Microbial Research (UCMR). Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
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2024 (English)In: Microbiology Spectrum, E-ISSN 2165-0497, Vol. 12, no 2, article id e02956-23Article in journal (Refereed) Published
Abstract [en]

Carbapenem-resistant Acinetobacter baumannii causes one of the most difficult-to-treat nosocomial infections. Polycationic drugs like polymyxin B or colistin and tetracycline drugs such as doxycycline or minocycline are commonly used to treat infections caused by carbapenem-resistant A. baumannii. Here, we show that a subpopulation of cells associated with the opaque/translucent colony phase variation by A. baumannii AB5075 displays differential tolerance to subinhibitory concentrations of colistin and tetracycline. Using a variety of microscopic techniques, we demonstrate that extracellular polysaccharide moieties mediate colistin tolerance to opaque A. baumannii at single-cell level and that mushroom-shaped biofilm structures protect opaque bacteria at the community level. The colony switch phenotype is found to alter several traits of A. baumannii, including long-term survival under desiccation, tolerance to ethanol, competition with Escherichia coli, and intracellular survival in the environmental model host Acanthamoeba castellanii. Additionally, our findings suggest that extracellular DNA associated with membrane vesicles can promote colony switching in a DNA recombinase-dependent manner.

Importance: As a WHO top-priority drug-resistant microbe, Acinetobacter baumannii significantly contributes to hospital-associated infections worldwide. One particularly intriguing aspect is its ability to reversibly switch its colony morphotype on agar plates, which has been remarkably underexplored. In this study, we employed various microscopic techniques and phenotypic assays to investigate the colony phase variation switch under different clinically and environmentally relevant conditions. Our findings reveal that the presence of a poly N-acetylglucosamine-positive extracellular matrix layer contributes to the protection of bacteria from the bactericidal effects of colistin. Furthermore, we provide intriguing insights into the multicellular lifestyle of A. baumannii, specifically in the context of colony switch variation within its predatory host, Acanthamoeba castellanii.

Place, publisher, year, edition, pages
American Society for Microbiology, 2024. Vol. 12, no 2, article id e02956-23
Keywords [en]
colisitin, opaque colony, translucent colony
National Category
Infectious Medicine Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-221121DOI: 10.1128/spectrum.02956-23ISI: 001141161500001PubMedID: 38205963Scopus ID: 2-s2.0-85184519514OAI: oai:DiVA.org:umu-221121DiVA, id: diva2:1839019
Funder
Swedish Research Council, 2020-06136Swedish Research Council, 2019-01720Swedish Research Council, 2018-02914Swedish Research Council, 2016-00968Swedish Research Council, 2019-00217The Kempe Foundations, SMK-1961The Swedish Foundation for International Cooperation in Research and Higher Education (STINT), IB2022-9222Swedish Cancer Society, 2017-419Available from: 2024-02-20 Created: 2024-02-20 Last updated: 2024-02-20Bibliographically approved

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Mushtaq, FizzaNadeem, AftabBala, AnjuKarah, NabilZlatkov, NikolaWai, Sun NyuntUhlin, Bernt EricAhmad, Irfan

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Mushtaq, FizzaNadeem, AftabBala, AnjuKarah, NabilZlatkov, NikolaWai, Sun NyuntUhlin, Bernt EricAhmad, Irfan
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Umeå Centre for Microbial Research (UCMR)Department of Molecular Biology (Faculty of Medicine)Molecular Infection Medicine Sweden (MIMS)
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Microbiology Spectrum
Infectious MedicineMicrobiology in the medical area

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