Biology subjects

Solhaug, A.

Publications and source records attributed to Solhaug, A..

4 recordsLinked to original sources

bioRxiv2026

From cellular stress to cytokine modulation: An in vitro study of intestinal effects of major Alternaria mycotoxins

Mycotoxins are frequently detected in food, making the gastrointestinal tract the first organ exposed. Here, we used various in vitro intestinal cell models to explore the barrier and immune responses to the Alternaria mycotoxins alternariol (AOH), alternariol methyl ether (AME), altenuene (ALT), altertoxin I (ATX-I), tentoxin (TEN), and tenuazonic acid (TeA). The mycotoxins exhibited low toxicity in undifferentiated Caco-2 cells, but AOH, AME, and ATX-I affected the cell cycle and reactive oxygen species (ROS) levels. None of the toxins alone or in combination with IL-1beta; had any effect on the barrier integrity or viability of the differentiated Caco-2/HT29-MTX-E12 co-culture. Furthermore, AOH and AME reduced IL-1beta-induced IL-8 secretion, whereas TeA increased the secretion, demonstrating immunomodulatory effects. For verification, we used the more in vivo-like EpiIntestinal TM model, which is based on human primary cells. AOH, AME, and TeA had minor effects on viability without compromising barrier integrity; also, cytokine secretion was less affected than in the co-culture model. Studies on uptake confirmed low absorption of AOH, AME, and TeA. Overall, the studies indicate a low absorption and moderate effects of the toxins on the gastrointestinal tract.

cell biology↗

bioRxiv2026

Evaluation of immunotoxic effects and metabolism of enniatins and beauvericin using in vitro models of the human intestinal epithelium

Enniatins (ENNs) and beauvericin (BEA) are mycotoxins produced by Fusarium species. They are frequently detected in cereal-based foods such as maize and wheat. Consequently, the gastrointestinal tract is a primary site of exposure for consumers of grain-containing foods. This study examined intestinal effects of four major ENNs: ENNB, ENNB1, ENNA, and ENNA1, and the structurally related mycotoxin BEA, using the primary human intestinal model EpiIntestinal (TM) tissues and a Caco-2/TH29-MTX-E12 co-culture. None of the compounds induced cytotoxicity or impaired the barrier integrity at concentrations ranging from 1 to 10 microM. Furthermore, all ENNs and BEA stimulated IL-6 secretion, with ENNA and ENNA1 inducing the strongest responses, while IL-8 secretion was only triggered by ENNA and ENNA1. Transport studies revealed that approximately 32% of ENNB and 25% of ENNB1 crossed from the apical to the basolateral side of the intestinal tissue within 4 h, whereas the other ENNs and BEA had transport ratios below 10%. Further findings suggested that uptake and intracellular accumulation of ENNs and BEA were influenced by their affinity to the efflux transporter P-glycoprotein (P-gp). In addition, several ENNB and ENNB1 metabolites were generated in the EpiIntestinal (TM) tissues and transported. Lastly, it was demonstrated that ENNB can disturb the metabolism of the sex hormone estradiol in human liver microsomes. Overall, ENNs and BEA showed limited acute toxicity in human intestinal models but elicited distinct inflammatory responses and differed in transport and metabolism. These findings may be of relevance when evaluating health risks from chronic, low-level dietary exposure

cell biology↗

bioRxiv2024

Insights into the nature of the microalgal toxins from the Chrysochromulina leadbeateri blooms in Northern Norwegian fjords

In May-June 2019, the microalga Chrysochromulina leadbeateri caused a massive fish-killing event in several fjords in Northern Norway, resulting in the largest direct impact ever on aquaculture in northern Europe due to toxic algae. Motivated by the fact that no algal toxins have previously been described from C. leadbeateri, we set out to investigate the chemical nature and toxicity of secondary metabolites in extracts of two strains (UIO 393, UIO 394) isolated from the 2019 bloom, as well as one older strain (UIO 035) isolated during a bloom in Northern Norway in 1991. Initial LC-DAD-MS/MS-based molecular networking analysis of the crude MeOH extracts of the cultivated strains showed that their profiles of small organic molecules, including a large number of known lipids, were very similar, suggesting that the same class of toxin(s) were likely the causative agents of the two harmful algal bloom (HAB) events. Next, bioassay-guided fractionation using the RTgill-W1 cell line and metabolomics analysis pointed to a major compound affording [M+H]+ ions at m/z 1399.8333 as a possible toxin, corresponding to a compound with the formula C67H127ClO27. Moreover, our study unveiled a series of minor analogues exhibiting distinct patterns of chlorination and sulfation, together defining a new family of compounds, which we propose to name leadbeaterins. Remarkably, these suspected toxins were detected in situ in samples collected during the 2019 bloom close to Tromso, thereby substantiating their likely role in fish kills. The elemental compositions of the putative C. leadbeateri ichthyotoxins strongly indicate them to be long linear polyhydroxylated polyketides, structurally similar to sterolysins, reported from a number of dinoflagellates.

ecology↗

bioRxiv2023

The infectious salmon anaemia virus esterase prunes erythrocyte surfaces in infected Atlantic salmon and exposes terminal sialic acids to lectin recognition

Many sialic acid-binding viruses express a receptor-destroying enzyme (RDE) that removes the virus-targeted receptor and limits viral interactions with the host cell surface. Despite a growing appreciation of how the viral RDE promotes viral fitness, little is known about its direct effects on the host. Infectious salmon anaemia virus (ISAV) attaches to 4-O-acetylated sialic acids on the surface of Atlantic salmon epithelial, endothelial, and red blood cells. ISAV receptor binding and destruction are effectuated by the same surface molecule, the haemagglutinin esterase (HE). We recently discovered a global loss of vascular 4-O-acetylated sialic acids in ISAV-infected fish. The loss correlated with the expression of viral proteins, giving rise to the hypothesis that it was mediated by the HE. Here, we report that the capacity to bind new ISAV particles is also progressively lost from circulating erythrocytes in infected fish. Furthermore, salmon erythrocytes exposed to ISAV ex vivo lost their capacity to bind new ISAV particles. The loss of ISAV binding was not associated with receptor saturation. Moreover, upon loss of the ISAV receptor, erythrocyte surfaces became more available to the lectin wheat germ agglutinin, suggesting a potential to alter interactions with endogenous lectins of similar specificity. The pruning of erythrocyte surfaces was inhibited by an antibody that prevented ISAV attachment. Furthermore, recombinant HE, but not an esterase-silenced mutant, was sufficient to induce the observed surface modulation. Our results directly link the ISAV-induced erythrocyte modulation to the hydrolytic activity of the HE and show that the observed effects are not mediated by endogenous esterases. Our findings are the first to directly link a viral esterase to extensive host cell surface modulation in infected individuals. This raises the question of how common the phenomenon is among sialic acid-binding viruses. It is also relevant to ask if the altered sialic acid landscape of the affected cells influences host biological functions with relevance to viral disease.

microbiology↗