Aspergillus fumigatus Fumagillin Contributes to Host Cell Damage

The activity of fumagillin, a mycotoxin produced by Aspergillus fumigatus, has not been studied in depth. In this study, we used a commercial fumagillin on cultures of two cell types (A549 pneumocytes and RAW 264.7 macrophages). This toxin joins its target, MetAP2 protein, inside cells and, as a result, significantly reduces the electron chain activity, the migration, and the proliferation ability on the A549 cells, or affects the viability and proliferation ability of the RAW 264.7 macrophages. However, the toxin stimulates the germination and double branch hypha production of fungal cultures, pointing out an intrinsic resistant mechanism to fumagillin of fungal strains. In this study, we also used a fumagillin non-producer A. fumigatus strain (∆fmaA) as well as its complemented strain (∆fmaA::fmaA) and we tested the fumagillin secretion of the fungal strains using an Ultra High-Performance Liquid Chromatography (UHPLC) method. Furthermore, fumagillin seems to protect the fungus against phagocytosis in vitro, and during in vivo studies using infection of immunosuppressed mice, a lower fungal burden in the lungs of mice infected with the ∆fmaA mutant was demonstrated.This research was funded by the Basque Government: grant number IT1362-19. X.G. and S.C.-S. received a Ph.D. fellowship from the Basque Government; and U.P.-C. from the University of the Basque Country

Mikroorganismoek minbizia eragin dezakete?

Many studies have analyzed relationships between microorganisms and cancer, demonstrating that microorganisms are able to prevent the onset of cancer and, others to provoke it. Specifically, more and more scientific articles are publishing on microorganisms, linking them to the creation, implementation and dispersion of cancer. In fact, it is estimated that microorganisms cause 17.8% of all cancers. The cancer-causing viral capability is the most studied and, in consequence, many different viral mechanisms that can cause cancer have been described. The International Cancer Re-search Institute has categorized eight viruses for the first time as "carcinogenic to hu-mans", including a human papillomavirus, two herpesvirus and two hepatitis viruses. Regarding bacteria, among cancerous agents, Helicobacter pylori is the most studied in relation to stomach cancer. In addition, many other bacteria, such as Salmonella typhi, Chlamydia pneumoniae and Streptococcus bovis, have been directly related to cancer. Although relatively little research on the effect of fungi on cancer has been investi-gated, some of the toxins produced by these microorganisms have been shown to cause cancer. In addition, some mechanism for the generation and spread of cancer have been described in Candida albicans. Studies to date have shown the influence of microor-ganisms on the development and promotion of cancer. For this reason, to face cancer in the next future, deepen into the relationship between cancer and microorganisms will be essential; Ikerketa askok mikroorganismoen eta minbizien arteko erlazioak aztertu dituzte, eta erakutsi dute mikroorganismo batzuek minbiziaren agerpena saihesten dutela eta beste batzuek, aldiz, minbizia eragin dezaketela. Hain zuzen ere, gero eta artikulu zientifiko gehiago argitaratzen ari dira mikroorganismoak minbiziaren sortzearekin, ezarpenarekin eta sakabanaketarekin erlazionatuz. Izan ere, mikroorganismoek minbizi guztien % 17,8 eragiten dutela estimatu da. Minbizia sortzeko birusen gaitasuna da gehien ikertu dena eta, ondorioz, minbizia sor dezaketen mekanismo desberdin asko deskribatu dira. Minbizia Ikertzeko Nazioarteko Agentziak zortzi birus 1. mailako "gizakiontzat kartzinogeno"-tzat sailkatu ditu; haien artean, giza papiloma birusa, bi herpesbirus eta bi hepatitisaren birus aurkitzen dira. Bakterioei dagokienez, minbizi-eragileen artean, Helicobacter pylori da gehien ikertu dena urdaileko minbiziarekin erlazionatuta. Baina honetaz gain, beste hainbat bakterio, hala nola Salmonella typhi, Chlamydia pneumoniae eta Streptococcus bovis minbiziarekin zuzenki erlazionatu dira. Onddoek daukaten minbiziarekiko erlazioa oso gutxi ikertu den arren, mikroorganismo hauek sortutako toxina batzuek minbizia eragin dezaketela frogatu da. Horrez gain, Candida albicans onddoak minbiziaren sorrera eta hedapena eragin dezakeen hainbat mekanismo deskribatu dira. Orain arte egindako ikerketek mikroorganismoek minbiziaren garapenean eta sustapenean daukaten eragina agerrarazi dute. Hori dela eta, etorkizunean minbiziari aurre egiteko, minbiziaren eta mikroorganismoen arteko erlazioan sakontzea ezinbestekoa da

<i>Candida albicans</i> increases the aerobic glycolysis and activates MAPK-dependent inflammatory response of liver sinusoidal endothelial cells

The liver, and more specifically, the liver sinusoidal endothelial cells, constitute the beginning of one of the most important responses for the elimination of hematogenously disseminated Candida albicans. Therefore, we aimed to study the mechanisms involved in the interaction between these cells and C. albicans. Transcriptomics-based analysis showed an increase in the expression of genes related to the immune response (including receptors, cytokines, and adhesion molecules), as well as to aerobic glycolysis. Further in vitro analyses showed that IL-6 production in response to C. albicans is controlled by MyD88- and SYK-pathways, suggesting an involvement of Toll-like and C-type lectin receptors and the subsequent activation of the MAP-kinases and c-Fos/AP-1 transcription factor. In addition, liver sinusoidal endothelial cells undergo metabolic reprogramming towards aerobic glycolysis induced by C. albicans, as confirmed by the increased Extracellular Acidification Rate and the overexpression of enolase (Eno2), hexonikase (Hk2) and glucose transporter 1 (Slc2a1). In conclusion, these results indicate that the hepatic endothelium responds to C. albicans by increasing aerobic glycolysis and promoting an inflammatory environment.</p

Study of Humoral Responses against Lomentospora/Scedosporium spp. and Aspergillus fumigatus to Identify L. prolificans Antigens of Interest for Diagnosis and Treatment

The high mortality rates of Lomentospora prolificans infections are due, above all, to the tendency of the fungus to infect weakened hosts, late diagnosis and a lack of effective therapeutic treatments. To identify proteins of significance for diagnosis, therapy or prophylaxis, immunoproteomics-based studies are especially important. Consequently, in this study murine disseminated infections were carried out using L. prolificans, Scedosporium aurantiacum, Scedosporium boydii and Aspergillus fumigatus, and their sera used to identify the most immunoreactive proteins of L. prolificans total extract and secreted proteins. The results showed that L. prolificans was the most virulent species and its infections were characterized by a high fungal load in several organs, including the brain. The proteomics study showed a high cross-reactivity between Scedosporium/Lomentospora species, but not with A. fumigatus. Among the antigens identified were, proteasomal ubiquitin receptor, carboxypeptidase, Vps28, HAD-like hydrolase, GH16, cerato-platanin and a protein of unknown function that showed no or low homology with humans. Finally, Hsp70 deserves a special mention as it was the main antigen recognized by Scedosporium/Lomentospora species in both secretome and total extract. In conclusion, this study identifies antigens of L. prolificans that can be considered as potential candidates for use in diagnosis and as therapeutic targets and the production of vaccines.This research was funded by the Basque Government, grant number IT1362-19. I.B., L.M.S. and L.A.F. received a predoctoral fellowship from the Basque Government