scholarly journals Spórafelszíni fehérjéket kódoló gének jellemzése Mucor circinelloides-ben

2021 ◽  
Author(s):  
Csilla Szebenyi

A Mucorales rend fajai által okozott gombás fertőzéseket mucormikózisnak nevezzük. Ez a ritka, humán megbetegedés leggyakrabban olyan betegeknél fordul elő, akik immunszuppresszív kezelés alatt állnak vagy vérképzőszervi rosszindulatú daganat szövődményeként immunhiányos állapotban szenvednek. A mucormikózis etiológiai ágenseként leggyakrabban azonosított fajok a Rhizopus, Lichtheimia és Mucor nemzetségekhez tartoznak. A gombás fertőzésekre fogékony populáció növekedése miatt a mucormikózisos esetek száma is növekvő tendenciát mutat. A kezelés sikeressége nagymértékben függ a korai diagnózistól és a megfelelően megválasztott gombaellenes terápiától, valamint a háttérben meghúzódó, immunrendszert gyengítő állapot kezelésétől. Legtöbbször azonban már a diagnózis felállítása is kihívást jelentő feladat. A Mucorales rend tagjai rezisztenciát mutatnak a rutinszerűen alkalmazott gombaellenes szerek többségével szemben (pl. echinokandinok és azolok). A fent említett tények mindegyike sürgetővé teszi az azonosítást lehetővé tevő molekuláris módszerek fejlesztését, valamint új gombaellenes célpontok keresését. Ehhez elengedhetetlen a mucormikózis patomechanizmusának tisztázása, a gazda-patogén interakciók feltárása, valamint a potenciális virulencia faktorok és biomarkerek azonosítása. E célok eléréséhez szükségszerű egy olyan molekuláris és genetikai manipulációs módszer járomspórás gombákra történő adaptációjára, mely segítségével rutinszerűen állíthatók elő a génfunkciók vizsgálatára alkalmas mutáns törzsek. A legfrissebb kutatások rámutattak a CotH fehérje család fontosságára a járomspórás Rhizopus delemar patogenitása kapcsán. Jelen munka elsősorban e géncsalád átfogó elemzésére, mint például a virulenciában betöltött szerepének tisztázására összpontosult. A Mucor genomban azonosított feltételezett spórafelszíni fehérjéknek azonban csak egy része mutatott homológiát azokkal a Rhizopus fehérjékkel, melyek kapcsolatban állnak a gomba patogenitásával. A CotH fehérjék funkcionális elemzése során nyomon követtük a CRISPR-Cas9 rendszer által létrehozott genetikailag stabil mutánsok fenotípusos változásait, hogy megválaszolhassuk azt a kérdést, hogy a CotH fehérjék milyen szerepet játszanak a Mucor circinelloides gomba patogenezisében, illetve egyéb fiziológiai folyamataiban.


Author(s):  
Teclegiorgis Gebremariam ◽  
Sondus Alkhazraji ◽  
Abdullah Alqarihi ◽  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
...  

There is increased concern that the quality, generalizability, and reproducibility of biomedical research can be influenced by the sex of animals used. We studied the differences between male and female mice in response to invasive pulmonary mucormycosis including susceptibility to infection, host immune reaction, and responses to antifungal therapy. We used diabetic ketoacidotic (DKA) or neutropenic mice infected with either Rhizopus delemar or Mucor circinelloides. The only difference detected was that when DKA mice were infected with M. circinelloides, female mice were more resistant to infection than male mice (median survival time of 5 vs. 2 days for female and male mice, respectively). However, a 100% lethality was detected among infected animals of both sexes. Treatment with either liposomal amphotericin B (L-AMB) or posaconazole (POSA) protected mice from infection and eliminated the difference seen between infected but untreated female and male mice. Treatment with L-AMB consistently outperformed POSA in prolonging survival and reducing tissue fungal burden of DKA and neutropenic mice infected with R. delemar or M. circinelloides, in both mouse sexes. Although little difference was detected in cytokine levels among both sexes, mucormycosis infection in the DKA mouse model induced more inflammatory cytokines/chemokines involved in neutrophil (CXCL1) and macrophage (CXCL2) recruitment vs. uninfected mice. As expected, this inflammatory response was reduced in the neutropenic mouse model. Our studies show that there are few differences between female and male DKA or neutropenic mice infected with mucormycosis with no effect on the outcome of treatment or host immune response.



2021 ◽  
Vol 7 (4) ◽  
pp. 313
Author(s):  
Teclegiorgis Gebremariam ◽  
Sondus Alkhazraji ◽  
Abdullah Alqarihi ◽  
Nathan P. Wiederhold ◽  
Laura K. Najvar ◽  
...  

There is increased concern that the quality, generalizability and reproducibility of biomedical research can be influenced by the sex of animals used. We studied the differences between male and female mice in response to invasive pulmonary mucormycosis including susceptibility to infection, host immune reaction and responses to antifungal therapy. We used diabetic ketoacidotic (DKA) or neutropenic mice infected with either Rhizopus delemar or Mucor circinelloides. The only difference detected was that when DKA mice were infected with M. circinelloides, female mice were more resistant to infection than male mice (median survival time of 5 vs. 2 days for female and male mice, respectively). However, a 100% lethality was detected among infected animals of both sexes. Treatment with either liposomal amphotericin B (L-AMB) or posaconazole (POSA) protected mice from infection and eliminated the difference seen between infected but untreated female and male mice. Treatment with L-AMB consistently outperformed POSA in prolonging survival and reducing tissue fungal burden of DKA and neutropenic mice infected with R. delemar or M. circinelloides, in both mouse sexes. While little difference was detected in cytokine levels among both sexes, mucormycosis infection in the DKA mouse model induced more inflammatory cytokines/chemokines involved in neutrophil (CXCL1) and macrophage (CXCL2) recruitment vs. uninfected mice. As expected, this inflammatory response was reduced in the neutropenic mouse model. Our studies show that there are few differences between female and male DKA or neutropenic mice infected with mucormycosis with no effect on the outcome of treatment or host immune response.



2020 ◽  
Vol 62 (1-2) ◽  
pp. 49-68
Author(s):  
T. O. Kondratiuk ◽  
T. V. Beregova ◽  
I. Yu. Parnikoza ◽  
S. Y. Kondratyuk ◽  
A. Thell

The identification of the diversity of microscopic fungi of lithobiont communities of the Argentine Islands in specimens collected during the 22nd Ukrainian Antarctic Expedition was the purpose of this work. Samples of rock, soil, mosses and lichens of rock micro-habitats of “Crustose lichen sub-formation and fruticose lichen and moss cushion sub-formation” were used in the work. These samples were used for extracting and cultivation of filamentous fungi on dense nutrient media. Determination of physiological and biochemical characteristics and identification of yeast-like fungi were performed using a microbiological analyser ‘Vitek-2’ (‘Bio Merieux’, France). Cultivation of microorganisms was carried out at temperatures from +2 to +37 °C. In results cultures of microscopic fungi of Zygomycota (Mucor circinelloides), Ascomycota (species of the genera cf. Tlielebolus, Talaromyces), representatives of the Anamorphic fungi group (Geomyces pannorum, species of the genera Alternaria, Acremonium, Aspergillus, Penicillium, and Cladosporium) were isolated from Antarctic samples. Microscopic fungi Penicillium spp. were dominated after the frequency in the studied samples (54.5%). Rhodotorula rubra and Candida sp. among isolated yeast fungi, and dark pigmented fungi represented by Aureobasidium pulhdans and Exophiala spp. were identified. The biological properties of a number of isolated fungi (the potential ability to synthesise important biologically active substances: melanins, carotenoids, lipids) are characterised. Mycobiota of rock communities of Argentine Islands is rich on filamentous and yeast fungi similarly to other regions of Antarctica. A number of fungi investigated are potentially able to synthesise biologically active substances. The dark pigmented species of the genera Cladosporium, Exophiala, Aureobasidium pulhdans, capable of melanin synthesis; ‘red’ yeast Rhodotorula rubra (carotenoid producers and resistant to toxic metals); Mucor circinelloides and Geomyces pannorum, lipid producers, are among these fungi. Yeast-like fungi assimilated a wide range of carbohydrates, which will allow them to be further used for cultivation in laboratory and process conditions. The collection of technologically promising strains of microorganisms, part of the Culture Collection of Fungi at Taras Shevchenko National University of Kyiv (Ukraine), is updated with isolated species (strains) of filamentous fungi and yeast – potential producers of biologically active substances, obtained within this study.



Author(s):  
Nathália Sá Alencar do Amaral Marques ◽  
Rafael de Souza Mendonça ◽  
Daylin Rubio Ribeaux ◽  
Antônio Vinicius Pinho Sá ◽  
Galba Maria Campos Takaki
Keyword(s):  




2002 ◽  
Vol 153 (3) ◽  
pp. 155-164 ◽  
Author(s):  
José L. Blasco ◽  
Marı́a A. Garcı́a-Sánchez ◽  
José Ruiz-Herrera ◽  
Arturo P. Eslava ◽  
Enrique A. Iturriaga


2017 ◽  
Vol 24 (10) ◽  
pp. 9681-9689 ◽  
Author(s):  
Liqun Sun ◽  
Xiufeng Cao ◽  
Min Li ◽  
Xu Zhang ◽  
Xinxin Li ◽  
...  


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