Candidiasis by Candida glabrata, Candida nivariensis and Candida bracarensis in Galleria mellonella: Virulence and Therapeutic Responses to Echinocandins

Candida albicans is the major etiological agent of invasive candidiasis but the increasing prevalence of emerging species of Candida, such as Candida glabrata and phylogenetically closely related species, Candida nivariensis and Candida bracarensis, requires special attention. Differences in virulence among these species and their therapeutic responses using in vivo non-mammalian models are scarcely analysed. The aim of this study was analyse the survival of G. mellonella and host-pathogen interactions during infection by C. glabrata, C. nivariensis and C. bracarensis. Moreover, therapeutic responses to echinocandins were also assessed in the G. mellonella model of candidiasis. These three species produced lethal infection in G. mellonella; C. glabrata was the most virulent species and C. bracarensis the less. Haemocytes of G. mellonella phagocytised C. bracarensis cells more effectively than those of the other two species. Treatment with caspofungin and micafungin was most effective to protect larvae during C. glabrata and C. nivariensis infections while anidulafungin was during C. bracarensis infection. The model of candidiasis in G. mellonella is simple and appropriate to assess the virulence and therapeutic response of these emerging Candida species. Moreover, it successfully allows for detecting differences in the immune system of the host depending on the virulence of pathogens.This research was supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) [SAF2017-86188-P and PID2020-117983RB-I00] and from the Consejería de Educación, Universidades e Investigación of Gobierno Vasco-Eusko Jaurlaritza [GIC15/78 IT-990-16]. Ainara Hernando-Ortiz was funded by Ph.D. grants from the University of the Basque Country (PIF 16/39)

Virulence of Candida Auris from Different Clinical Origins in Caenorhabditis Elegans and Galleria Mellonella Host Models

Candida auris is an emerging multidrug-resistant fungal pathogen responsible for nosocomial outbreaks of invasive candidiasis. Although several studies on the pathogenicity of this species have been reported, the knowledge on C. auris virulence is still limited. This study aims to analyze the pathogenicity of C. auris, using one aggregating isolate and eleven non-aggregating isolates from different clinical origins (blood, urine and oropharyngeal specimens) in two alternative host models of candidiasis: Caenorhabditis elegans and Galleria mellonella. Furthermore, possible associations between virulence, aggregation, biofilm-forming capacity, and clinical origin were assessed. The aggregating phenotype isolate was less virulent in both in vivo invertebrate infection models than non-aggregating isolates but showed higher capacity to form biofilms. Blood isolates were significantly more virulent than those isolated from urine and respiratory specimens in the G. mellonella model of candidiasis. We conclude that both models of candidiasis present pros and cons but prove useful to evaluate the virulence of C. auris in vivo. Both models also evidence the heterogeneity in virulence that this species can develop, which may be influenced by the aggregative phenotype and clinical origin.This work was supported by the Euskal Herriko Unibertsitatea [PIF 16/39]; Euskal Herriko Unibertsitatea [PIF17/167]; Eusko Jaurlaritza [GIC15/78 IT-990-16]; Ministerio de Economia y Competitividad [SAF2017-86188-P]

Modelos de candidiasis invasiva en Caenorhabditis elegans y Galleria mellonella para el estudio de la virulencia de especies emergentes de Candida y de la actividad de los fármacos antifúngicos

377 p.Candida albicans kandidiasi inbaditzailearen eragile ohikoena da. Hala ere, beste espezie batzuk, Candida glabrata eta Candida auris kasu, patogeno oportunista garrantzitsuak bihurtu dira. Alderdi ekonomikoek, logistikoek eta etikoek animalia ornodunen erabilera gero eta gehiago murrizten dutenez, ordezko ereduak, hala nola, Caenorhabditis elegans nematodoak eta Galleria mellonella lepidopteroaren larbak, garrantzi berezia hartu dute. Doktorego-tesi honen helburua C. elegans eta G. mellonellaren erabilgarritasuna ikertzea izan zen kandidiasi inbaditzailearen eredu gisa, bai C. glabrata, Candida nivariensis, Candida bracarensis eta C. aurisen birulentzia aztertzeko, zein espezie horiek eragiten dituzten kandidiasien aurkako tratamendu antifungikoaren eraginkortasuna ebaluatzeko.Bi in vivo eredu horiek erabilgarriak izan ziren Candidaren espezie emergenteen birulentzia aztertzeko. C. glabrata espeziea harreman filogenetiko estua duten C. nivariensis eta C. bracarensis espezieak baino birulentoagoa izan zen. Gainera, G. mellonellaren hemozitoek C. bracarensisen aurka eragindako berezko erantzuna eraginkorragoa izan zen C. glabrata eta C. nivariensisen aurka eragindakoa baino. Fenotipo ez-agregatzailea zuten C. auris espeziearen isolamenduak, fenotipo agregatzailea zuen isolamendua baino birulentoagoak izan ziren bi kandidiasi-ereduetan. Odol-jatorriko C. aurisen isolamenduak gernu- eta orofaringe-jatorrikoak baino birulentoagoak izan ziren G. mellonella kandidiasi-ereduan.C. elegans eta G. mellonella kandidiasi-eredu baliagarriak izan ziren kandidiasien aurkako tratamendu antifungikoak ikertzeko. B anfoterizina eta azolak farmako eraginkorrenak izan ziren C. glabrata eta C. bracarensis espezieek eragindako infekzioen aurka C. elegans ereduan, ekinokandinak, berriz, aktiboenak izan ziren C. nivariensis espezieak eragindakoen aurkakoak. Ekinokandinen tratamenduan, kaspofungina eta mikafungina eraginkorrenak izan ziren C. glabrata eta C. nivariensis infekzioen aurka G. mellonella ereduan. C. bracarensis infekzioen aurka, aldiz, anidulafungina izan zen eraginkorrena. B anfoterizinaren eta ekinokandinen arteko konbinazioa eraginkorra izan zen C. auris espeziak eragindako infekzioen aurka C. elegans kandidiasi-ereduan, B anfoterizinaren eta kaspofunginaren arteko konbinazioa kandidiasi-eredu horretan erabilitako hiru konbinazioen artean eraginkorrena izan zelarikCandida albicans es la causa más común de candidiasis invasiva. Sin embargo, otras especies, como Candida glabrata y Candida auris, se han convertido en patógenos oportunistas importantes. Los modelos de candidiasis en animales invertebrados, como el nematodo Caenorhabditis elegans y la larva del lepidoptero Galleria mellonella, han cobrado especial relevancia por evitar las restricciones éticas ligadas a los modelos murinos y proporcionar interesantes ventajas económicas, logísticas y de fácil manejo en el laboratorio. El objetivo del presente trabajo de Tesis doctoral fue estudiar la utilidad de C. elegans y G. mellonella como modelos de candidiasis invasiva para analizar la virulencia de C. glabrata, Candida nivariensis, Candida bracarensis y C. auris, y para evaluar la efectividad del tratamiento antifúngico contra las candidiasis que causan.Ambos modelos in vivo fueron útiles para el estudio de la virulencia de las especies emergentes de Candida. La especie C. glabrata fue más virulenta que sus especies filogenéticamente relacionadas, C. nivariensis y C. bracarensis. Además, la respuesta innata mediada por los hemocitos de G. mellonella fue más eficaz contra C. bracarensis que contra C. glabrata y C. nivariensis. Los aislamientos de la especie emergente C. auris con fenotipo no agregante fueron más virulentos que el aislamiento con fenotipo agregante en ambos modelos de candidiasis. Los aislamientos de C. auris provenientes de sangre fueron más virulentos que los provenientes de orina y orofaríngeos en el modelo de candidiasis en G. mellonella.Los modelos de candidiasis en C. elegans y G. mellonella fueron útiles para evaluar la terapia antifúngica contra las candidiasis. La anfotericina B y los azoles fueron los más activos contra la infección por C. glabrata y C. bracarensis, mientras que las equinocandinas lo fueron contra C. nivariensis en el modelo en C. elegans. En el tratamiento con equinocandinas, la caspofungina y la micafungina fueron más eficaces contra C. glabrata y C. nivariensis, mientras que la anidulafungina lo fue contra C. bracarensis en el modelo en G. mellonella. La combinación de anfotericina B y equinocandinas fue eficaz contra la infección por C. auris en el modelo de candidiasis en C. elegans, siendo la combinación de anfotericina B y caspofungina la más eficaz de las tres ensayadas en el modelo de candidiasis en C. elegans

Candidiasis by <i>Candida glabrata</i>, <i>Candida nivariensis</i> and <i>Candida bracarensis</i> in <i>Galleria mellonella</i>: Virulence and Therapeutic Responses to Echinocandins

Candida albicans is the major etiological agent of invasive candidiasis but the increasing prevalence of emerging species of Candida, such as Candida glabrata and phylogenetically closely related species, Candida nivariensis and Candida bracarensis, requires special attention. Differences in virulence among these species and their therapeutic responses using in vivo non-mammalian models are scarcely analysed. The aim of this study was analyse the survival of G. mellonella and host-pathogen interactions during infection by C. glabrata, C. nivariensis and C. bracarensis. Moreover, therapeutic responses to echinocandins were also assessed in the G. mellonella model of candidiasis. These three species produced lethal infection in G. mellonella; C. glabrata was the most virulent species and C. bracarensis the less. Haemocytes of G. mellonella phagocytised C. bracarensis cells more effectively than those of the other two species. Treatment with caspofungin and micafungin was most effective to protect larvae during C. glabrata and C. nivariensis infections while anidulafungin was during C. bracarensis infection. The model of candidiasis in G. mellonella is simple and appropriate to assess the virulence and therapeutic response of these emerging Candida species. Moreover, it successfully allows for detecting differences in the immune system of the host depending on the virulence of pathogens

Person verification by fusion of prosodic, voice spectral and facial parameters

Comunicació presentada a: SECRYPT 2006, International Conference on Security and Cryptography, celebrada a Setúbal, Portugal, del 7 al 10 d'agost de 2006Prosodic information can be used successfully for automatic speaker recognition, although most of the speaker recognition systems use only short-term spectral features as voice information. In this work, prosody information is added to a multimodal system based on face and voice characteristics in order to improve the performance of the system. Fusion is carried out by using various fusion strategies and two different fusion techniques: support vector machines and matcher weighting. Results are clearly improved when a previous normalization based on histogram equalization is done before the fusion of the monomodal scores.This work has been partially supported by the European Union (under CHIL IST-2002-506909 and BIOSEC IST-2002-001766) and by the Spanish Government (under ACESCA project TIN2005-08852 and grant AP2003-3598)

On the fusion of prosody, voice spectrum and face features for multimodal person verification

Comunicació presentada a: 9th International Conference on Spoken Language Processing; 17-21 de setembre de 2006 a Pittsburgh, Estats Units d'AmèricaMultimodal person recognition systems normally use shortterm spectral features as voice information. In this paper prosodic information is added to a system based on face and voice spectrum features. By using two fusion techniques, support vector machines and matcher weighting, different fusion strategies based on the fusion of monomodal scores in several steps are proposed. The performance of the system is clearly improved when the prosodic information is added and the best results are achieved when prosodic scores are previously fused and the resulting scores are fused again with spectral and facial scores. Speech and face scores have been obtained upon Switchboard-I and XM2VTS databases respectively

On the fusion of prosody, voice spectrum and face features for multimodal person verification

Comunicació presentada a: 9th International Conference on Spoken Language Processing; 17-21 de setembre de 2006 a Pittsburgh, Estats Units d'AmèricaMultimodal person recognition systems normally use shortterm spectral features as voice information. In this paper prosodic information is added to a system based on face and voice spectrum features. By using two fusion techniques, support vector machines and matcher weighting, different fusion strategies based on the fusion of monomodal scores in several steps are proposed. The performance of the system is clearly improved when the prosodic information is added and the best results are achieved when prosodic scores are previously fused and the resulting scores are fused again with spectral and facial scores. Speech and face scores have been obtained upon Switchboard-I and XM2VTS databases respectively

Cuadernos de pedagogía

Resumen basado en el de la publicación.La Escuela en Desescalada es un laboratorio de acompañamiento y cocreación entre docentes que se articula en torno al trabajo en equipos vinculados a retos, al que se une un proceso de facilitación y mentoría, y que confluye en el diseño final de diversas propuestas concretas para que la escuela pueda arrancar y avanzar durante el curso 2020-2021. El laboratorio se organiza en torno a 10 retos que recogen diez inquietudes derivadas de la «nueva normalidad» escolar a la que se deberán enfrentar alumnos, docentes y familias. La primera red de docentes participantes ha generado como resultado diez propuestas prácticas de aplicación en los centros que permiten responder a las nuevas preguntas y situaciones a las que se enfrenta la comunidad educativa y que se irán enriqueciendo con nuevas soluciones derivadas de próximas ediciones de este proceso.Biblioteca del Ministerio de Educación y Formación Profesional; Calle San Agustín 5; 28014 Madrid; Tel. +34917748000; [email protected]

Galleria mellonella insektua eta Caenorhabditis elegans nematodoa, infekzio eredu boteretsuak Candida glabrata eta erlazionatutako espezieen birulentzia ikertzeko.

Candidiasis is a mycotic infection caused by species of Candida genus. Candida albicans is the major aetiological agent, although other species of Candida, such as Candida glabrata, are considered emerging causes of this disease. The species, Candida bracarensis and Candida nivariensis, are phylogenetically similar to Candida glabrata and can be correctly differentiated by molecular techniques. These changes in the aetiology have serious implications for diagnosis, treatment and prognosis; considering that yeast pathogenesis or susceptibilities to current antifungal drugs may be different. Invertebrate models, such as the nematode Caenorhabditis elegans and the lepidopter Galleria mellonella, are an attractive alternative for the study of fungal pathogenesis and antifungal therapy. The aim of this research study was to evaluate the usefulness of these two non-convetional model to assess the in vivo virulence of the phylogenetically close-related species, Candida glabrata, Candida bracarensis and Candida nivariensis.; Kandidiasia Candida generoko espezieek eragindako infekzio mikotikoa da. Candida albicans agente etiologiko nagusia da baina gero eta gehiagotan Candida generoko beste espezie batzuk agertzen ari dira kandidiasiaren eragile bezala eta, hauen artean, Candida glabrata espeziea. Espezie honekin lotuta beste bi espezie daude, Candida bracarensis eta Candida nivariensis, teknika molekularrek ondo desberdindu ditzaketenak. Aldaketa etiologiko hauek ondorio larriak izan ditzakete kandidiasiaren diagnostikoan, tratamenduan edota pronostikoan, besteak beste, bere patogenia edo antifungikoekiko sentikortasuna oso desberdina izan daitezkeelako. Ordezko eredu esperimentalek erabiliz mikroorganismoek eragindako gaixotasunen patogenia eta terapia ezagutzeko ezinbesteko aukera ematen dizkigute, eta hauen artean, Caenorhabditis elegans nematodoa eta Galleria mellonella lepidopteroa ditugu. Ikerketa lan honetan konbentzionalak ez diren bi animalia eredu hauen erabilgarritasuna ebaluatu nahi izan da Candida glabrata, Candida bracarensis eta Candida nivariensis harreman filogenetiko estua duten hiru espezie hauen birulentzia in vivo aztertzeko

Caenorhabditis elegans as a Model System To Assess Candida glabrata, Candida nivariensis, and Candida bracarensis Virulence and Antifungal Efficacy

Although Candida albicans remains the major etiological agent of invasive candidiasis, Candida glabrata and other emerging species of Candida are increasingly isolated. This species is the second most prevalent cause of candidiasis in many regions of the world. However, clinical isolates of Candida nivariensis and Candida bracarensis can be misidentified and are underdiagnosed due to phenotypic traits shared with C. glabrata. Little is known about the two cryptic species. Therefore, pathogenesis studies are needed to understand their virulence traits and their susceptibility to antifungal drugs. The susceptibility of Caenorhabditis elegans to different Candida species makes this nematode an excellent model for assessing host-fungus interactions. We evaluated the usefulness of C. elegans as a nonconventional host model to analyze the virulence of C. glabrata, C. nivariensis, and C. bracarensis. The three species caused candidiasis, and the highest virulence of C. glabrata was confirmed. Furthermore, we determined the efficacy of current antifungal drugs against the infection caused by these species in the C. elegans model. Amphotericin B and azoles showed the highest activity against C. glabrata and C. bracarensis infections, while echinocandins were more active for treating those caused by C. nivariensis. C. elegans proved to be a useful model system for assessing the pathogenicity of these closely related species.This work was supported by the Consejería de Educación, Universidades e Investigación (GIC15/78 IT-990-16) of Gobierno Vasco-Eusko Jaurlaritza. A. Hernando-Ortiz was funded by a Ph.D. grant from the University of the Basque Country (PIF 16/39)