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  1. Article ; Online: Pseudomonas aeruginosa adaptation and evolution in patients with cystic fibrosis.

    Rossi, Elio / La Rosa, Ruggero / Bartell, Jennifer A / Marvig, Rasmus L / Haagensen, Janus A J / Sommer, Lea M / Molin, Søren / Johansen, Helle Krogh

    Nature reviews. Microbiology

    2020  Volume 19, Issue 5, Page(s) 331–342

    Abstract: Intense genome sequencing of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) airways has shown inefficient eradication of the infecting bacteria, as well as previously undocumented patient-to-patient transmission of adapted clones. However, ... ...

    Abstract Intense genome sequencing of Pseudomonas aeruginosa isolates from cystic fibrosis (CF) airways has shown inefficient eradication of the infecting bacteria, as well as previously undocumented patient-to-patient transmission of adapted clones. However, genome sequencing has limited potential as a predictor of chronic infection and of the adaptive state during infection, and thus there is increasing interest in linking phenotypic traits to the genome sequences. Phenotypic information ranges from genome-wide transcriptomic analysis of patient samples to determination of more specific traits associated with metabolic changes, stress responses, antibiotic resistance and tolerance, biofilm formation and slow growth. Environmental conditions in the CF lung shape both genetic and phenotypic changes of P. aeruginosa during infection. In this Review, we discuss the adaptive and evolutionary trajectories that lead to early diversification and late convergence, which enable P. aeruginosa to succeed in this niche, and we point out how knowledge of these biological features may be used to guide diagnosis and therapy.
    MeSH term(s) Biological Evolution ; Cystic Fibrosis/microbiology ; Genome, Bacterial ; Humans ; Pseudomonas Infections/microbiology ; Pseudomonas aeruginosa/genetics ; Pseudomonas aeruginosa/physiology
    Language English
    Publishing date 2020-11-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2139054-X
    ISSN 1740-1534 ; 1740-1526
    ISSN (online) 1740-1534
    ISSN 1740-1526
    DOI 10.1038/s41579-020-00477-5
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 5865: Show issues Location:
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  2. Article ; Online: Primary ciliary dyskinesia patients have the same

    Arndal, Elisabeth / Johansen, Helle K / Haagensen, Janus A J / Bartell, Jennifer A / Marvig, Rasmus L / Alanin, Mikkel / Aanæs, Kasper / Høiby, Niels / Nielsen, Kim G / Backer, Vibeke / von Buchwald, Christian

    The European respiratory journal

    2020  Volume 55, Issue 1

    MeSH term(s) Cilia ; Ciliary Motility Disorders ; Clone Cells ; Humans ; Kartagener Syndrome/diagnosis ; Lung ; Paranasal Sinuses ; Pseudomonas aeruginosa
    Language English
    Publishing date 2020-01-16
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 639359-7
    ISSN 1399-3003 ; 0903-1936
    ISSN (online) 1399-3003
    ISSN 0903-1936
    DOI 10.1183/13993003.01472-2019
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    Zs.MO 292: Show issues

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  3. Article ; Online: Evolutionary highways to persistent bacterial infection.

    Bartell, Jennifer A / Sommer, Lea M / Haagensen, Janus A J / Loch, Anne / Espinosa, Rocio / Molin, Søren / Johansen, Helle Krogh

    Nature communications

    2019  Volume 10, Issue 1, Page(s) 629

    Abstract: Persistent infections require bacteria to evolve from their naïve colonization state by optimizing fitness in the host via simultaneous adaptation of multiple traits, which can obscure evolutionary trends and complicate infection management. Accordingly, ...

    Abstract Persistent infections require bacteria to evolve from their naïve colonization state by optimizing fitness in the host via simultaneous adaptation of multiple traits, which can obscure evolutionary trends and complicate infection management. Accordingly, here we screen 8 infection-relevant phenotypes of 443 longitudinal Pseudomonas aeruginosa isolates from 39 young cystic fibrosis patients over 10 years. Using statistical modeling, we map evolutionary trajectories and identify trait correlations accounting for patient-specific influences. By integrating previous genetic analyses of 474 isolates, we provide a window into early adaptation to the host, finding: (1) a 2-3 year timeline of rapid adaptation after colonization, (2) variant "naïve" and "adapted" states reflecting discordance between phenotypic and genetic adaptation, (3) adaptive trajectories leading to persistent infection via three distinct evolutionary modes, and (4) new associations between phenotypes and pathoadaptive mutations. Ultimately, we effectively deconvolute complex trait adaptation, offering a framework for evolutionary studies and precision medicine in clinical microbiology.
    MeSH term(s) Biological Evolution ; Cystic Fibrosis/microbiology ; Humans ; Models, Statistical ; Mutation/genetics ; Pseudomonas Infections/genetics ; Pseudomonas aeruginosa/pathogenicity
    Language English
    Publishing date 2019-02-07
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-019-08504-7
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  4. Article ; Online: Evolutionary highways to persistent bacterial infection

    Jennifer A. Bartell / Lea M. Sommer / Janus A. J. Haagensen / Anne Loch / Rocio Espinosa / Søren Molin / Helle Krogh Johansen

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 13

    Abstract: The pathogen Pseudomonas aeruginosa undergoes complex trait adaptation within cystic fibrosis patients. Here, Bartell, Sommer, and colleagues use statistical modeling of longitudinal isolates to characterize the joint genetic and phenotypic evolutionary ... ...

    Abstract The pathogen Pseudomonas aeruginosa undergoes complex trait adaptation within cystic fibrosis patients. Here, Bartell, Sommer, and colleagues use statistical modeling of longitudinal isolates to characterize the joint genetic and phenotypic evolutionary trajectories of P. aeruginosa within hosts.
    Keywords Science ; Q
    Language English
    Publishing date 2019-02-01T00:00:00Z
    Publisher Nature Publishing Group
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Evolutionary highways to persistent bacterial infection

    Jennifer A. Bartell / Lea M. Sommer / Janus A. J. Haagensen / Anne Loch / Rocio Espinosa / Søren Molin / Helle Krogh Johansen

    Nature Communications, Vol 10, Iss 1, Pp 1-

    2019  Volume 13

    Abstract: The pathogen Pseudomonas aeruginosa undergoes complex trait adaptation within cystic fibrosis patients. Here, Bartell, Sommer, and colleagues use statistical modeling of longitudinal isolates to characterize the joint genetic and phenotypic evolutionary ... ...

    Abstract The pathogen Pseudomonas aeruginosa undergoes complex trait adaptation within cystic fibrosis patients. Here, Bartell, Sommer, and colleagues use statistical modeling of longitudinal isolates to characterize the joint genetic and phenotypic evolutionary trajectories of P. aeruginosa within hosts.
    Keywords Science ; Q
    Language English
    Publishing date 2019-02-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Effects of Resonant Electromagnetic Fields on Biofilm Formation in Pseudomonas aeruginosa

    Janus A. J. Haagensen / Michael Bache / Livio Giuliani / Nikolaj S. Blom

    Applied Sciences, Vol 11, Iss 7760, p

    2021  Volume 7760

    Abstract: The global rise of antimicrobial resistance (AMR) constitutes a future health threat and dictates a need to explore alternative and non-chemical approaches. The aim of this study was to explore the use of weak resonant electromagnetic fields as a method ... ...

    Abstract The global rise of antimicrobial resistance (AMR) constitutes a future health threat and dictates a need to explore alternative and non-chemical approaches. The aim of this study was to explore the use of weak resonant electromagnetic fields as a method to disrupt biofilm formation of a pathogenic bacterium in cystic fibrosis patients. We developed a bioresonance laboratory setup able to distinguish between changes in planktonic growth and changes in biofilm formation and showed that certain resonant frequencies were able to affect biofilm formation without affecting planktonic growth. In addition, we show that the ambient day-to-day magnetic field affects biofilm formation in a non-consistent manner. Overall, we conclude that our assay is suitable for studying the potential of resonant magnetic fields as a treatment and prevention strategy to prevent biofilm infections, and that certain resonant frequencies may be used as future medical applications to combat antimicrobial resistance.
    Keywords bioresonance ; antimicrobial resistance ; microbial biofilm ; infection ; ion cyclotron resonance ; Technology ; T ; Engineering (General). Civil engineering (General) ; TA1-2040 ; Biology (General) ; QH301-705.5 ; Physics ; QC1-999 ; Chemistry ; QD1-999
    Subject code 535
    Language English
    Publishing date 2021-08-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Bacterial Cell Cultures in a Lab-on-a-Disc: A Simple and Versatile Tool for Quantification of Antibiotic Treatment Efficacy.

    Serioli, Laura / Laksafoss, Trygvi Z / Haagensen, Janus A J / Sternberg, Claus / Soerensen, Mads P / Molin, Søren / Zór, Kinga / Boisen, Anja

    Analytical chemistry

    2020  Volume 92, Issue 20, Page(s) 13871–13879

    Abstract: Pathogenic bacterial biofilms can be life-threatening, greatly decrease patient's quality of life, and are a substantial burden on the healthcare system. Current methods for evaluation of antibacterial treatments in clinics ... ...

    Abstract Pathogenic bacterial biofilms can be life-threatening, greatly decrease patient's quality of life, and are a substantial burden on the healthcare system. Current methods for evaluation of antibacterial treatments in clinics and
    MeSH term(s) Anti-Bacterial Agents/pharmacology ; Batch Cell Culture Techniques/instrumentation ; Batch Cell Culture Techniques/methods ; Biofilms/drug effects ; Biofilms/growth & development ; Biomass ; Lab-On-A-Chip Devices ; Microscopy, Confocal/methods ; Pseudomonas aeruginosa/physiology
    Chemical Substances Anti-Bacterial Agents
    Keywords covid19
    Language English
    Publishing date 2020-10-01
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1508-8
    ISSN 1520-6882 ; 0003-2700
    ISSN (online) 1520-6882
    ISSN 0003-2700
    DOI 10.1021/acs.analchem.0c02582
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    Zs.A 4033: Show issues Location:
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  8. Article ; Online: Co-delivery of ciprofloxacin and colistin using microcontainers for bacterial biofilm treatment.

    Birk, Stine Egebro / Mazzoni, Chiara / Mobasharah Javed, Madeeha / Borre Hansen, Morten / Krogh Johansen, Helle / Anders Juul Haagensen, Janus / Molin, Søren / Hagner Nielsen, Line / Boisen, Anja

    International journal of pharmaceutics

    2021  Volume 599, Page(s) 120420

    Abstract: In many infected patients, bacterial biofilms represent a mode of growth that significantly enhances the tolerance to antimicrobials, leaving the patients with difficult-to-cure infections. Therefore, there is a growing need for effective treatment ... ...

    Abstract In many infected patients, bacterial biofilms represent a mode of growth that significantly enhances the tolerance to antimicrobials, leaving the patients with difficult-to-cure infections. Therefore, there is a growing need for effective treatment strategies to combat biofilm infections. In this work, reservoir-based microdevices, also known as microcontainers (MCs), are co-loaded with two antibiotics: ciprofloxacin hydrochloride (CIP) and colistin sulfate (COL), targeting both metabolically active and dormant subpopulations of the biofilm. We assess the effect of the two drugs in a time-kill study of planktonic P. aeruginosa and find that co-loaded MCs are superior to monotherapy, resulting in complete killing of the entire population. Biofilm consortia of P. aeruginosa grown in flow chambers were not fully eradicated. However, antibiotics in MCs work significantly faster than simple perfusion of antibiotics (62.5 ± 8.3% versus 10.6 ± 10.1% after 5 h) in biofilm consortia, showing the potential of the MC-based treatment to minimize the use of antimicrobials in future therapies.
    MeSH term(s) Anti-Bacterial Agents ; Biofilms ; Ciprofloxacin ; Colistin ; Humans ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa
    Chemical Substances Anti-Bacterial Agents ; Ciprofloxacin (5E8K9I0O4U) ; Colistin (Z67X93HJG1)
    Language English
    Publishing date 2021-02-27
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 428962-6
    ISSN 1873-3476 ; 0378-5173
    ISSN (online) 1873-3476
    ISSN 0378-5173
    DOI 10.1016/j.ijpharm.2021.120420
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    Zs.A 1409: Show issues Location:
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  9. Article: Advanced microscopy of microbial cells.

    Haagensen, Janus A J / Regenberg, Birgitte / Sternberg, Claus

    Advances in biochemical engineering/biotechnology

    2011  Volume 124, Page(s) 21–54

    Abstract: Growing awareness of heterogeneity in cells of microbial populations has emphasized the importance of advanced microscopy for visualization and understanding of the molecular mechanisms underlying cell-to-cell variation. In this review, we highlight some ...

    Abstract Growing awareness of heterogeneity in cells of microbial populations has emphasized the importance of advanced microscopy for visualization and understanding of the molecular mechanisms underlying cell-to-cell variation. In this review, we highlight some of the recent advances in confocal microscopy, super-resolution optical microscopy (STED, SIM, PALM) as well as atomic force microscopy and Raman spectroscopy. Using examples of bistability in microbial populations as well as biofilm development and differentiation in bacterial and yeast consortia, we demonstrate the importance of microscopy for visualization of variation between cells in phenotypic traits such as gene expression.
    MeSH term(s) Bacteria/cytology ; Bacteria/metabolism ; Cell Tracking/methods ; Fungi/cytology ; Fungi/metabolism ; Image Enhancement/methods ; Imaging, Three-Dimensional/methods ; Microscopy/methods ; Molecular Imaging/methods
    Language English
    Publishing date 2011
    Publishing country Germany
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ISSN 0724-6145
    ISSN 0724-6145
    DOI 10.1007/10_2010_83
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  10. Article ; Online: Development of Spatial Distribution Patterns by Biofilm Cells.

    Haagensen, Janus A J / Hansen, Susse K / Christensen, Bjarke B / Pamp, Sünje J / Molin, Søren

    Applied and environmental microbiology

    2015  Volume 81, Issue 18, Page(s) 6120–6128

    Abstract: Confined spatial patterns of microbial distribution are prevalent in nature, such as in microbial mats, soil communities, and water stream biofilms. The symbiotic two-species consortium of Pseudomonas putida and Acinetobacter sp. strain C6, originally ... ...

    Abstract Confined spatial patterns of microbial distribution are prevalent in nature, such as in microbial mats, soil communities, and water stream biofilms. The symbiotic two-species consortium of Pseudomonas putida and Acinetobacter sp. strain C6, originally isolated from a creosote-polluted aquifer, has evolved a distinct spatial organization in the laboratory that is characterized by an increased fitness and productivity. In this consortium, P. putida is reliant on microcolonies formed by Acinetobacter sp. C6, to which it attaches. Here we describe the processes that lead to the microcolony pattern by Acinetobacter sp. C6. Ecological spatial pattern analyses revealed that the microcolonies were not entirely randomly distributed and instead were arranged in a uniform pattern. Detailed time-lapse confocal microscopy at the single-cell level demonstrated that the spatial pattern was the result of an intriguing self-organization: small multicellular clusters moved along the surface to fuse with one another to form microcolonies. This active distribution capability was dependent on environmental factors (carbon source and oxygen) and historical contingency (formation of phenotypic variants). The findings of this study are discussed in the context of species distribution patterns observed in macroecology, and we summarize observations about the processes involved in coadaptation between P. putida and Acinetobacter sp. C6. Our results contribute to an understanding of spatial species distribution patterns as they are observed in nature, as well as the ecology of engineered communities that have the potential for enhanced and sustainable bioprocessing capacity.
    MeSH term(s) Acinetobacter/physiology ; Biofilms/growth & development ; Microbial Consortia ; Microscopy, Confocal ; Pseudomonas putida/physiology ; Time-Lapse Imaging
    Language English
    Publishing date 2015-09
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 223011-2
    ISSN 1098-5336 ; 0099-2240
    ISSN (online) 1098-5336
    ISSN 0099-2240
    DOI 10.1128/AEM.01614-15
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