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Csu pili dependent biofilm formation and virulence of 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). 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: 0000-0003-3318-9084
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2023 (English)In: npj Biofilms and Microbiomes, E-ISSN 2055-5008, Vol. 9, no 1, article id 101Article in journal (Refereed) Published
Abstract [en]

Acinetobacter baumannii has emerged as one of the most common extensive drug-resistant nosocomial bacterial pathogens. Not only can the bacteria survive in hospital settings for long periods, but they are also able to resist adverse conditions. However, underlying regulatory mechanisms that allow A. baumannii to cope with these conditions and mediate its virulence are poorly understood. Here, we show that bi-stable expression of the Csu pili, along with the production of poly-N-acetyl glucosamine, regulates the formation of Mountain-like biofilm-patches on glass surfaces to protect bacteria from the bactericidal effect of colistin. Csu pilus assembly is found to be an essential component of mature biofilms formed on glass surfaces and of pellicles. By using several microscopic techniques, we show that clinical isolates of A. baumannii carrying abundant Csu pili mediate adherence to epithelial cells. In addition, Csu pili suppressed surface-associated motility but enhanced colonization of bacteria into the lungs, spleen, and liver in a mouse model of systemic infection. The screening of c-di-GMP metabolizing protein mutants of A. baumannii 17978 for the capability to adhere to epithelial cells led us to identify GGDEF/EAL protein AIS_2337, here denoted PdeB, as a major regulator of Csu pili-mediated virulence and biofilm formation. Moreover, PdeB was found to be involved in the type IV pili-regulated robustness of surface-associated motility. Our findings suggest that the Csu pilus is not only a functional component of mature A. baumannii biofilms but also a major virulence factor promoting the initiation of disease progression by mediating bacterial adherence to epithelial cells.

Place, publisher, year, edition, pages
Springer Nature, 2023. Vol. 9, no 1, article id 101
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:umu:diva-218629DOI: 10.1038/s41522-023-00465-6PubMedID: 38097635Scopus ID: 2-s2.0-85179677116OAI: oai:DiVA.org:umu-218629DiVA, id: diva2:1822693
Funder
Swedish Research Council, 2020-06136Swedish Research Council, 2020-06136Swedish Research Council, 2018-02914Swedish Research Council, 2022-04779The Kempe Foundations, SMK-1961The Kempe Foundations, SMK21-0076Umeå University, FS 2.1.6–1776-19Umeå University, 2021-2023The Swedish Foundation for International Cooperation in Research and Higher Education (STINT)Swedish Cancer Society, 2017-419Available from: 2023-12-27 Created: 2023-12-27 Last updated: 2023-12-27Bibliographically approved

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Ahmad, IrfanNadeem, AftabMushtaq, FizzaZlatkov, NikolaWai, Sun NyuntUhlin, Bernt Eric

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Ahmad, IrfanNadeem, AftabMushtaq, FizzaZlatkov, NikolaWai, Sun NyuntUhlin, Bernt Eric
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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 in the medical area

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