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Per- and polyfluoroalkyl substances enhance Staphylococcus aureus pathogenicity and impair host immune response
Örebro universitet, Institutionen för naturvetenskap och teknik. (The Life Science Centre-Biology)ORCID-id: 0000-0003-1850-1412
School of Science and Technology, Örebro University, Örebro, Sweden. (The Life Science Centre-Biology)
Örebro universitet, Institutionen för naturvetenskap och teknik. (The Life Science Centre-Biology)ORCID-id: 0000-0001-7336-6335
Örebro universitet, Institutionen för naturvetenskap och teknik. (The Life Science Centre-Biology)ORCID-id: 0000-0001-7957-0310
2022 (Engelska)Ingår i: Environmental Pollution, ISSN 0269-7491, E-ISSN 1873-6424, Vol. 314, artikel-id 120294Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Per- and Poly-fluoroalkyl substances (PFAS) are one of the major persistent environmental contaminants. Epidemiological studies have linked PFAS exposures to altered immunity and increased occurrence of infections in children. However, the mechanisms leading to immune susceptibility to bacterial infections remains unclear. To elucidate the mechanism, transcriptional alteration in the Caenorhabditis elegans model caused by a PFAS contaminated environmental water and two reconstituted PFAS solutions were evaluated using RNA-sequencing. PFAS affected the expression of several genes involved in C. elegans immune surveillance to Gram-positive bacteria (cpr-2, tag-38, spp-1, spp-5, clec-7, clec-172). The combined exposure to PFAS and Staphylococcus aureus significantly reduced C. elegans survival and increased intestinal membrane permeability. Furthermore, the growth of S. aureus in the presence of PFAS increased the expression of virulence genes, specifically, the virulence gene regulator saeR and α-hemolysin, hla, which resulted in increased hemolytic activity. The present study demonstrated that PFAS exposure not only increased C. elegans susceptibility to pathogens by reducing host immunity and increasing intestinal membrane permeability, but also increased bacteria virulence. This presents a broader implication for humans and other animals, where environmental contaminants simultaneously reduce host resilience, while, increasing microbial pathogenicity.

Ort, förlag, år, upplaga, sidor
Springer, 2022. Vol. 314, artikel-id 120294
Nyckelord [en]
C. elegans, Hemolysin, Immune suppression, PFAS, S. aureus
Nationell ämneskategori
Biokemi Molekylärbiologi
Identifikatorer
URN: urn:nbn:se:oru:diva-101604DOI: 10.1016/j.envpol.2022.120294ISI: 000882962000004PubMedID: 36181932Scopus ID: 2-s2.0-85139329946OAI: oai:DiVA.org:oru-101604DiVA, id: diva2:1700598
Forskningsfinansiär
KK-stiftelsen, 20180027 20140180Örebro universitetTillgänglig från: 2022-10-03 Skapad: 2022-10-03 Senast uppdaterad: 2025-02-20Bibliografiskt granskad
Ingår i avhandling
1. Influence of gut microbiota on xenobiotic toxicity in a Caenorhabditis elegans model with a focus on arsenic and PFAS
Öppna denna publikation i ny flik eller fönster >>Influence of gut microbiota on xenobiotic toxicity in a Caenorhabditis elegans model with a focus on arsenic and PFAS
2023 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Exposure to environmental toxins presents a hazard to humans. Inorganic metalloid- arsenic (As), organic chemicals- per and poly-fluoroalkyl substances (PFAS) are frequently detected in the environment. Exposure to As and PFAS is associated with multiple adverse effects in humans and animals. However, little attention has been given to the interaction between host microbiota and pollutants. Gut microbiota interactions with the host and xenobiotics, is hy-pothesized to decrease xenobiotic toxicity. However, the role of microbiota on host responses during these exposure scenarios is poorly understood. Therefore, the aim was to study the influence of gut microbes on Caenorhabditis elegans responses using As and PFAS as environmental toxins. Specific objectives were to study the role of single microbes, and simple three microbe combinations with tractable diversity in nematode responses to As and PFAS. The study examined C. elegans physiological responses to As in the presence of single As resistant microbe Lysinibacillus sphaericus (Paper I) and simple 3-bacteria combinations (Paper IV). These studies showed that gut microbes decrease As toxicity and increase nematode survival through mediating host stress responses and fat metabolism. Combinations of microbes with toxins in microbiota also affect lifespan (Paper III). Furthermore, effects of PFAS mixtures were also analyzed on C. elegans and pathogen Staphylococcus aureus (Paper II); and role of gut microbe combinations during exposures to PFOS (Paper V). Exposure to PFAS/ PFOS increased virulence of pathogens and decreased host immunity, stress response and survival with opportunists; with non-pathogens C. elegans showed increased stress response and lived longer. These results emphasized that gut microbes contribute to alter xenobiotic toxicity in the host. Finally, this thesis presents novel insights into the role of gut microbes in modulating host physiological responses during As and PFAS exposures.

Ort, förlag, år, upplaga, sidor
Örebro: Örebro University, 2023. s. 86
Serie
Örebro Studies in Life Science, ISSN 1653-3100 ; 19
Nyckelord
C. elegans, physiological responses, gut microbe models, arse-nite, arsenate, PFAS, PFOS
Nationell ämneskategori
Annan biologi
Identifikatorer
urn:nbn:se:oru:diva-102436 (URN)9789175294827 (ISBN)
Disputation
2023-01-19, Örebro universitet, Forumhuset, Hörsal F, Fakultetsgatan 1, Örebro, 13:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2022-11-28 Skapad: 2022-11-28 Senast uppdaterad: 2023-01-26Bibliografiskt granskad

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Mangu, JagadishOlsson, Per-ErikJass, Jana

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