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Müller, Daniel C.
Publications (2 of 2) Show all publications
Müller, D. C., Kauppi, A., Edin, A., Gylfe, Å., Sjöstedt, A. B. & Johansson, A. (2019). Phospholipid Levels in Blood during Community-Acquired Pneumonia. PLoS ONE, 14(5), Article ID e0216379.
Open this publication in new window or tab >>Phospholipid Levels in Blood during Community-Acquired Pneumonia
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2019 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 14, no 5, article id e0216379Article in journal (Refereed) Published
Abstract [en]

Phospholipids, major constituents of bilayer cell membranes, are present in large amounts in pulmonary surfactant and play key roles in cell signaling. Here, we aim at finding clinically useful disease markers in community-acquired pneumonia (CAP) using comprehensive phospholipid profiling in blood and modeling of changes between sampling time points. Serum samples from 33 patients hospitalized with CAP were collected at admission, three hours after the start of intravenous antibiotics, Day 1 (at 12–24 h), Day 2 (at 36–48 h), and several weeks after recovery. A profile of 75 phospholipid species including quantification of the bioactive lysophosphatidylcholines (LPCs) was determined using liquid chromatography coupled to time-of-flight mass spectrometry. To control for possible enzymatic degradation of LPCs, serum autotaxin levels were examined. Twenty-two of the 33 patients with a clinical diagnosis of CAP received a laboratory-verified CAP diagnosis by microbial culture or microbial DNA detection by qPCR. All major phospholipid species, especially the LPCs, were pronouncedly decreased in the acute stage of illness. Total and individual LPC concentrations increased shortly after the initiation of antibiotic treatment, concentrations were at their lowest 3h after the initiation, and increased after Day 1. The total LPC concentration increased by a change ratio of 1.6–1.7 between acute illness and Day 2, and by a ratio of 3.7 between acute illness and full disease resolution. Autotaxin levels were low in acute illness and showed little changes over time, contradicting a hypothesis of enzymatic degradation causing the low levels of LPCs. In this sample of patients with CAP, the results demonstrate that LPC concentration changes in serum of patients with CAP closely mirrored the early transition from acute illness to recovery after the initiation of antibiotics. LPCs should be further explored as potential disease stage biomarkers in CAP and for their potential physiological role during recovery.

Place, publisher, year, edition, pages
Public Library of Science, 2019
Keywords
Community-acquired pneumonia, phospholipids, infection, diagnosis, metabolomics
National Category
Infectious Medicine
Identifiers
urn:nbn:se:umu:diva-147058 (URN)10.1371/journal.pone.0216379 (DOI)000467148400025 ()31063483 (PubMedID)
Note

Originally included in thesis in manuscript form 

Available from: 2018-04-25 Created: 2018-04-25 Last updated: 2019-06-12Bibliographically approved
Hosseinzadeh, A., Stylianou, M., Lopes, J. P., Müller, D. C., Häggman, A., Holmberg, S., . . . Urban, C. F. (2019). Stable Redox-Cycling Nitroxide Tempol has Antifungal and Immune-modulatory Properties. Frontiers in Microbiology, 10, Article ID 1843.
Open this publication in new window or tab >>Stable Redox-Cycling Nitroxide Tempol has Antifungal and Immune-modulatory Properties
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2019 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 10, article id 1843Article in journal (Refereed) Published
Abstract [en]

Invasive mycoses remain underdiagnosed and difficult to treat. Hospitalized individuals with compromised immunity increase in number and constitute the main risk group for severe fungal infections. Current antifungal therapy is hampered by slow and insensitive diagnostics and frequent toxic side effects of standard antifungal drugs. Identification of new antifungal compounds with high efficacy and low toxicity is therefore urgently required. We investigated the antifungal activity of tempol, a cell-permeable nitroxide. To narrow down possible mode of action we used RNA-seq technology and metabolomics to probe for pathways specifically disrupted in the human fungal pathogen Candida albicans due to tempol administration. We found genes upregulated which are involved in iron homeostasis, mitochondrial stress, steroid synthesis, and amino acid metabolism. In an ex vivo whole blood infection, tempol treatment reduced C. albicans colony forming units and at the same time increased the release of pro-inflammatory cytokines, such as interleukin 8 (IL-8, monocyte chemoattractant protein-1, and macrophage migration inhibitory factor). In a systemic mouse model, tempol was partially protective with a significant reduction of fungal burden in the kidneys of infected animals during infection onset. The results obtained propose tempol as a promising new antifungal compound and open new opportunities for the future development of novel therapies.

Keywords
antifungal activity, redox active, immunomodulators, candidiasis, Candida albicans, Candida glabrata
National Category
Microbiology in the medical area
Research subject
Infectious Diseases
Identifiers
urn:nbn:se:umu:diva-151596 (URN)10.3389/fmicb.2019.01843 (DOI)000481763300001 ()31481939 (PubMedID)
Funder
Swedish Research Council, 2014-02281The Kempe Foundations, 1453
Note

Originally included in thesis in manuscript form 

Available from: 2018-09-07 Created: 2018-09-07 Last updated: 2019-10-11Bibliographically approved
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