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Backman, Emelie
Publications (6 of 6) Show all publications
Unger, L., Skoluda, S., Backman, E., Amulic, B., Ponce-Garcia, F. M., Etiaba, C. N. .., . . . Urban, C. F. (2023). Candida albicans induces neutrophil extracellular traps and leucotoxic hypercitrullination via candidalysin. EMBO Reports, 24(11), Article ID e57571.
Open this publication in new window or tab >>Candida albicans induces neutrophil extracellular traps and leucotoxic hypercitrullination via candidalysin
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2023 (English)In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 24, no 11, article id e57571Article in journal (Refereed) Published
Abstract [en]

The peptide toxin candidalysin, secreted by Candida albicans hyphae, promotes stimulation of neutrophil extracellular traps (NETs). However, candidalysin alone triggers a distinct mechanism for NET-like structures (NLS), which are more compact and less fibrous than canonical NETs. Candidalysin activates NADPH oxidase and calcium influx, with both processes contributing to morphological changes in neutrophils resulting in NLS formation. NLS are induced by leucotoxic hypercitrullination, which is governed by calcium-induced protein arginine deaminase 4 activation and initiation of intracellular signalling events in a dose- and time-dependent manner. However, activation of signalling by candidalysin does not suffice to trigger downstream events essential for NET formation, as demonstrated by lack of lamin A/C phosphorylation, an event required for activation of cyclin-dependent kinases that are crucial for NET release. Candidalysin-triggered NLS demonstrate anti-Candida activity, which is resistant to nuclease treatment and dependent on the deprivation of Zn2+. This study reveals that C. albicans hyphae releasing candidalysin concurrently trigger canonical NETs and NLS, which together form a fibrous sticky network that entangles C. albicans hyphae and efficiently inhibits their growth.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
chronic granulomatous disease, fungal immunology, histone citrullination, polymorphonuclear leucocytes, reactive oxygen species
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-215387 (URN)10.15252/embr.202357571 (DOI)001081020500001 ()37795769 (PubMedID)2-s2.0-85173538219 (Scopus ID)
Funder
Swedish Research Council, VR-MH2018-05909Swedish Research Council, VR-MH2020-01764Swedish Research Council, VR-MH2022-00850The Kempe Foundations, CK-2033,U16Wellcome trust, 214229_Z_18_ZGerman Research Foundation (DFG), 390713860Swedish Research Council, 2019-01123Swedish Heart Lung Foundation, 2019-01123Stiftelsen Konung Gustaf V:s 80-årsfondRegion Västra Götaland, TUAGBG-917531
Available from: 2023-10-30 Created: 2023-10-30 Last updated: 2024-01-04Bibliographically approved
Shchukarev, A., Backman, E., Watts, S., Salentinig, S., Urban, C. F. & Ramstedt, M. (2021). Applying Cryo-X-ray Photoelectron Spectroscopy to Study the Surface Chemical Composition of Fungi and Viruses. Frontiers in Chemistry, 9, Article ID 666853.
Open this publication in new window or tab >>Applying Cryo-X-ray Photoelectron Spectroscopy to Study the Surface Chemical Composition of Fungi and Viruses
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2021 (English)In: Frontiers in Chemistry, E-ISSN 2296-2646, Vol. 9, article id 666853Article in journal (Refereed) Published
Abstract [en]

Interaction between microorganisms and their surroundings are generally mediated via the cell wall or cell envelope. An understanding of the overall chemical composition of these surface layers may give clues on how these interactions occur and suggest mechanisms to manipulate them. This knowledge is key, for instance, in research aiming to reduce colonization of medical devices and device-related infections from different types of microorganisms. In this context, X-ray photoelectron spectroscopy (XPS) is a powerful technique as its analysis depth below 10 nm enables studies of the outermost surface structures of microorganism. Of specific interest for the study of biological systems is cryogenic XPS (cryo-XPS). This technique allows studies of intact fast-frozen hydrated samples without the need for pre-treatment procedures that may cause the cell structure to collapse or change due to the loss of water. Previously, cryo-XPS has been applied to study bacterial and algal surfaces with respect to their composition of lipids, polysaccharides and peptide (protein and/or peptidoglycan). This contribution focuses onto two other groups of microorganisms with widely different architecture and modes of life, namely fungi and viruses. It evaluates to what extent existing models for data treatment of XPS spectra can be applied to understand the chemical composition of their very different surface layers. XPS data from model organisms as well as reference substances representing specific building blocks of their surface were collected and are presented. These results aims to guide future analysis of the surface chemical composition of biological systems.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2021
Keywords
cryo-XPS, virus, fungi, reference data, bacteriophage, surface chemistry, cell wall
National Category
Other Chemistry Topics Biophysics Physical Chemistry Microbiology Other Medical Biotechnology
Identifiers
urn:nbn:se:umu:diva-183667 (URN)10.3389/fchem.2021.666853 (DOI)000660083200001 ()34124001 (PubMedID)2-s2.0-85107576942 (Scopus ID)
Funder
The Kempe Foundations, JCK-1720
Available from: 2021-05-28 Created: 2021-05-28 Last updated: 2023-03-24Bibliographically approved
Shankar, M., Uwamahoro, N., Backman, E., Holmberg, S., Niemiec, M. J., Roth, J., . . . Urban, C. F. (2021). Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis. Frontiers in Immunology, 12, Article ID 553911.
Open this publication in new window or tab >>Immune Resolution Dilemma: Host Antimicrobial Factor S100A8/A9 Modulates Inflammatory Collateral Tissue Damage During Disseminated Fungal Peritonitis
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2021 (English)In: Frontiers in Immunology, E-ISSN 1664-3224, Vol. 12, article id 553911Article in journal (Refereed) Published
Abstract [en]

Intra-abdominal infection (peritonitis) is a leading cause of severe disease in surgical intensive care units, as over 70% of patients diagnosed with peritonitis develop septic shock. A critical role of the immune system is to return to homeostasis after combating infection. S100A8/A9 (calprotectin) is an antimicrobial and pro-inflammatory protein complex used as a biomarker for diagnosis of numerous inflammatory disorders. Here we describe the role of S100A8/A9 in inflammatory collateral tissue damage (ICTD). Using a mouse model of disseminated intra-abdominal candidiasis (IAC) in wild-type and S100A8/A9-deficient mice in the presence or absence of S100A9 inhibitor paquinimod, the role of S100A8/A9 during ICTD and fungal clearance were investigated. S100A8/A9-deficient mice developed less ICTD than wild-type mice. Restoration of S100A8/A9 in knockout mice by injection of recombinant protein resulted in increased ICTD and fungal clearance comparable to wild-type levels. Treatment with paquinimod abolished ICTD and S100A9-deficient mice showed increased survival compared to wild-type littermates. The data indicates that S100A8/A9 controls ICTD levels and antimicrobial activity during IAC and that targeting of S100A8/A9 could serve as promising adjunct therapy against this challenging disease.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2021
Keywords
Candida albicans, host-pathogen interactions, host-targeted agents, inflammation, peritonitis, S100A8/A9 complex, sepsis
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-181798 (URN)10.3389/fimmu.2021.553911 (DOI)000627778800001 ()2-s2.0-85102439343 (Scopus ID)
Funder
The Kempe Foundations, SMK-1453Swedish Research Council, VR-M 2017-01681Swedish Research Council, 2014-02281
Available from: 2021-04-01 Created: 2021-04-01 Last updated: 2024-01-17Bibliographically approved
Urban, C. F. & Backman, E. (2020). Eradicating, retaining, balancing, swarming, shuttling and dumping: a myriad of tasks for neutrophils during fungal infection. Current Opinion in Microbiology, 58, 106-115
Open this publication in new window or tab >>Eradicating, retaining, balancing, swarming, shuttling and dumping: a myriad of tasks for neutrophils during fungal infection
2020 (English)In: Current Opinion in Microbiology, ISSN 1369-5274, E-ISSN 1879-0364, Vol. 58, p. 106-115Article in journal (Refereed) Published
Abstract [en]

Opportunistic, invasive mycoses in immunocompromised patients remain challenging for health care with unacceptably high levels of morbidity and mortality. Neutrophils are essential in host protection against invasive mycoses. Upon development of acute infection, neutrophils are recruited from circulation to the infected tissue, where they exert a considerable variety of effector functions with the ultimate task to eradicate invading microbes. Effector functions include recognition, phagocytosis and intracellular killing of microorganisms via oxidative and non-oxidative mechanisms, excretion of antimicrobial factors from intracellular storages (degranulation), release of neutrophil extracellular traps (NETs) and of extracellular vesicles (EVs), as well as generation of cytokines and chemokines to modulate immune responses. Herein, we describe recent findings which further our understanding of the roles of neutrophils during opportunistic fungal infections which could serve as starting point for the development of immune-targeted interventions to improve clinical management of affected individuals.

Place, publisher, year, edition, pages
Elsevier, 2020
National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-176945 (URN)10.1016/j.mib.2020.09.011 (DOI)000601245600016 ()33091824 (PubMedID)2-s2.0-85092790416 (Scopus ID)
Funder
Swedish Research Council, 2017-01681
Available from: 2020-11-20 Created: 2020-11-20 Last updated: 2023-03-23Bibliographically approved
Lopes, J. P., Stylianou, M., Backman, E., Holmberg, S., Ekoff, M., Nilsson, G. & Urban, C. F. (2019). Cryptococcus neoformans Induces MCP-1 Release and Delays the Death of Human Mast Cells. Frontiers in Cellular and Infection Microbiology, 9, Article ID 289.
Open this publication in new window or tab >>Cryptococcus neoformans Induces MCP-1 Release and Delays the Death of Human Mast Cells
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2019 (English)In: Frontiers in Cellular and Infection Microbiology, E-ISSN 2235-2988, Vol. 9, article id 289Article in journal (Refereed) Published
Abstract [en]

Cryptococcosis, caused by the basidiomycete Cryptococcus neoformans, is a life-threatening disease affecting approximately one million people per year worldwide. Infection can occur when C. neoformans cells are inhaled by immunocompromised people. In order to establish infection, the yeast must bypass recognition and clearance by immune cells guarding the tissue. Using in vitro infections, we characterized the role of mast cells (MCs) in cryptococcosis. We found that MCs recognize C. neoformans and release inflammatory mediators such as tryptase and cytokines. From the latter group MCs released mainly CCL-2/MCP-1, a strong chemoattractant for monocytic cells. We demonstrated that supernatants of infected MCs recruit monocytes but not neutrophils. During infection with C. neoformans, MCs have a limited ability to kill the yeast depending on the serotype. C. neoformans, in turn, modulates the lifespan of MCs both, by presence of its polysaccharide capsule and by secreting soluble modulators. Taken together, MCs might have important contributions to fungal clearance during early stages of cryptocococis where these cells regulate recruitment of monocytes to mucosal tissues.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2019
Keywords
innate immunity, Cryptococcus neoformans, mast cells, monocytes, monocyte chemoattractant protein 1/CCL-2, fungi
National Category
Immunology in the medical area Microbiology in the medical area
Identifiers
urn:nbn:se:umu:diva-162849 (URN)10.3389/fcimb.2019.00289 (DOI)000480550400001 ()31456952 (PubMedID)2-s2.0-85071629810 (Scopus ID)
Available from: 2019-09-06 Created: 2019-09-06 Last updated: 2023-03-24Bibliographically approved
Lopes, J. P., Stylianou, M., Backman, E., Holmberg, S., Jass, J., Claesson, R. & Urban, C. F. (2018). Evasion of Immune Surveillance in Low Oxygen Environments Enhances Candida albicans Virulence.. mBio, 9(6), Article ID e02120-18.
Open this publication in new window or tab >>Evasion of Immune Surveillance in Low Oxygen Environments Enhances Candida albicans Virulence.
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2018 (English)In: mBio, ISSN 2161-2129, E-ISSN 2150-7511, Vol. 9, no 6, article id e02120-18Article in journal (Refereed) Published
Abstract [en]

Microbial colonizers of humans have evolved to adapt to environmental cues and to sense nutrient availability. Oxygen is a constantly changing environmental parameter in different host tissues and in different types of infection. We describe how Candida albicans, an opportunistic fungal pathogen, can modulate the host response under hypoxia and anoxia. We found that high infiltration of polymorphonuclear leukocytes (PMNs) to the site of infection contributes to a low oxygen milieu in a murine subdermal abscess. A persistent hypoxic environment did not affect viability or metabolism of PMNs. Under oxygen deprivation, however, infection with C. albicans disturbed specific PMN responses. PMNs were not able to efficiently phagocytose, produce ROS, or release extracellular DNA traps. Failure to launch an adequate response was caused by C. albicans cell wall masking of β-glucan upon exposure to low oxygen levels which hindered PAMP sensing by Dectin-1 on the surfaces of PMNs. This in turn contributed to immune evasion and enhanced fungal survival. The cell wall masking effect is prolonged by the accumulation of lactate produced by PMNs under low oxygen conditions. Finally, adaptation to oxygen deprivation increased virulence of C. albicans which we demonstrated using a Caenorhabditis elegans infection model.IMPORTANCE Successful human colonizers have evolved mechanisms to bypass immune surveillance. Infiltration of PMNs to the site of infection led to the generation of a low oxygen niche. Exposure to low oxygen levels induced fungal cell wall masking, which in turn hindered pathogen sensing and antifungal responses by PMNs. The cell wall masking effect was prolonged by increasing lactate amounts produced by neutrophil metabolism under oxygen deprivation. In an invertebrate infection model, C. albicans was able to kill infected C. elegans nematodes within 2 days under low oxygen conditions, whereas the majority of uninfected controls and infected worms under normoxic conditions survived. These results suggest that C. albicans benefited from low oxygen niches to increase virulence. The interplay of C. albicans with innate immune cells under these conditions contributed to the overall outcome of infection. Adaption to low oxygen levels was in addition beneficial for C. albicans by reducing susceptibility to selected antifungal drugs. Hence, immunomodulation of host cells under low oxygen conditions could provide a valuable approach to improve current antifungal therapies.

Place, publisher, year, edition, pages
American Society for Microbiology, 2018
Keywords
Candida albicans, PMN, abscesses, anoxia, beta-glucan, fungal cell wall, fungal masking, hypoxia, immune evasion, mycology, neutrophil
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:umu:diva-153288 (URN)10.1128/mBio.02120-18 (DOI)000454730100052 ()30401781 (PubMedID)2-s2.0-85056284180 (Scopus ID)
Funder
Swedish Research Council, VR-M 2014-02281Swedish Research Council, 2017-01681The Kempe Foundations, SMK-1453Helge Ax:son Johnsons stiftelse Knowledge Foundation, 20140180
Available from: 2018-11-16 Created: 2018-11-16 Last updated: 2023-03-24Bibliographically approved
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