MycopathologiaPub Date : 2024-07-11DOI: 10.1007/s11046-024-00868-9
Bahgat Fayed, Sarra B Shakartalla, Hassan Sabbah, Hala Dalle, Mohamed Tannira, Abiola Senok, Sameh S M Soliman
{"title":"Transcriptome Analysis of Human Dermal Cells Infected with Candida auris Identified Unique Pathogenesis/Defensive Mechanisms Particularly Ferroptosis.","authors":"Bahgat Fayed, Sarra B Shakartalla, Hassan Sabbah, Hala Dalle, Mohamed Tannira, Abiola Senok, Sameh S M Soliman","doi":"10.1007/s11046-024-00868-9","DOIUrl":"10.1007/s11046-024-00868-9","url":null,"abstract":"<p><p>Candida auris is an emerging multi-drug resistant yeast that can cause life-threatening infections. A recent report clarified the ability of C. auris to form a biofilm with enhanced drug resistance properties in the host skin's deep layers. The formed biofilm may initiate further bloodstream spread and immune escape. Therefore, we propose that secreted chemicals from the biofilm may facilitate fungal pathogenesis. In response to this interaction, the host skin may develop potential defensive mechanisms. Comparative transcriptomics was performed on the host dermal cells in response to indirect interaction with C. auris biofilm through Transwell inserts compared to planktonic cells. Furthermore, the effect of antifungals including caspofungin and fluconazole was studied. The obtained data showed that the dermal cells exhibited different transcriptional responses. Kyoto Encyclopedia of Genes and Genomes and Reactome analyses identified potential defensive responses employed by the dermal cells and potential toxicity induced by C. auris. Additionally, our data indicated that the dominating toxic effect was mediated by ferroptosis; which was validated by qRT-PCR, cytotoxicity assay, and flow cytometry. On the other hand, the viability of C. auris biofilm was enhanced and accompanied by upregulation of MDR1, and KRE6 upon interaction with dermal cells; both genes play significant roles in drug resistance and biofilm maturation, respectively. This study for the first-time shed light on the dominating defensive responses of human dermal cells, microbe colonization site, to C. auris biofilm and its toxic effects. Further, it demonstrates how C. auris biofilm responds to the defensive mechanisms developed by the human dermal cells.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MycopathologiaPub Date : 2024-07-11DOI: 10.1007/s11046-024-00861-2
Maiken Cavling Arendrup, Jesus Guinea, Joseph Meletiadis
{"title":"Twenty Years in EUCAST Anti-Fungal Susceptibility Testing: Progress & Remaining Challenges.","authors":"Maiken Cavling Arendrup, Jesus Guinea, Joseph Meletiadis","doi":"10.1007/s11046-024-00861-2","DOIUrl":"10.1007/s11046-024-00861-2","url":null,"abstract":"<p><p>Since its inception in 2002, the EUCAST Antifungal Susceptibility Testing Subcommittee (AFST) has developed and refined susceptibility testing methods for yeast, moulds and dermatophytes, and established epidemiological cut-off values and breakpoints for antifungals. For yeast, three challenges have been addressed. Interpretation of trailing growth in fluconazole susceptibility testing, which has been proven without impact on efficacy if below the 50% endpoint. Variability in rezafungin MIC testing due to laboratory conditions, which has been solved by the addition of Tween 20 to the growth medium in E.Def 7.4. And third, interpretation of MICs for rare yeast with no breakpoints, where recommendations have been established for MIC-based clinical advice. For moulds, refinements include the validation of spectrophotometer reading for A. fumigatus to facilitate objective MIC determination, and for dermatophytes the establishment of a microdilution method with automated reading and a selective medium to minimise the risk of contaminations. Recent initiatives involve development and validation of agar-based screening assays for detection of potential azole and echinocandin resistance in A. fumigatus and Aspergillus species, respectively, and of terbinafine resistance in Trichophyton species. Moreover, the development of a EUCAST guidance document for molecular resistance testing represents an advancement, particularly for identifying target gene alterations associated with resistance. In summary, EUCAST AFST continues to play a pivotal role in standardizing AFST and facilitating accurate interpretation of susceptibility data for clinical decision-making. Adoption of EUCAST breakpoints for commercial test methods, however, requires thorough validation to ensure concordance with EUCAST reference testing species-specific MIC distributions.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Metagenomic Next-Generation Sequencing as an Effective Diagnostic Tool for Talaromycosis in HIV-Negative Patients.","authors":"Li Jiang, Tian-Wei Liang, Najwa Al-Odaini, Yuan Hu, Minli Huang, Lili Wei, Xiu-Ying Li, Kai-Su Pan, Dong-Yan Zheng, Zhi-Wen Jiang, Gao Wei, Cun-Wei Cao","doi":"10.1007/s11046-024-00866-x","DOIUrl":"10.1007/s11046-024-00866-x","url":null,"abstract":"<p><p>The diagnosis of Talaromyces marneffei infection in HIV-negative patients remains challenging. There is an urgent need for rapid and convenient methods to diagnose this complicated disease. The aim of this study was to evaluate the diagnostic efficiency of metagenomic next-generation sequencing (mNGS) for talaromycosis in non-HIV-infected patients by comparing mNGS with traditional microbial culture. In total, 66 samples from 57 patients were analyzed via both mNGS and microbial culture. The ROC curve showed a sensitivity for mNGS of 97.22%, which was greater than that of microbial culture (61.11%). Samples from the respiratory tract, infectious skin lesions, and lymph nodes are recommended as routine samples for talaromycosis detection via mNGS. Furthermore, mNGS significantly reduced the diagnostic time compared to microbial culture. Overall, our study demonstrated that mNGS is a promising tool for rapid and accurate pathogenic detection in HIV-negative patients with talaromycosis.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141563881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MycopathologiaPub Date : 2024-07-03DOI: 10.1007/s11046-024-00869-8
Bram Spruijtenburg, Antonio Rezusta, Jos Houbraken, Ferry Hagen, Theun de Groot, Jacques F Meis, Eelco F J Meijer
{"title":"Susceptibility Testing of Environmental and Clinical Aspergillus sydowii Demonstrates Potent Activity of Various Antifungals.","authors":"Bram Spruijtenburg, Antonio Rezusta, Jos Houbraken, Ferry Hagen, Theun de Groot, Jacques F Meis, Eelco F J Meijer","doi":"10.1007/s11046-024-00869-8","DOIUrl":"10.1007/s11046-024-00869-8","url":null,"abstract":"<p><p>The genus Aspergillus consists of a vast number of medically and environmentally relevant species. Aspergillus species classified in series Versicolores are ubiquitous in the environment and include the opportunistic pathogen Aspergillus sydowii, which is associated with onychomycosis and superficial skin infections. Despite frequent clinical reports of A. sydowii and related series Versicolores species, antifungal susceptibility data are scarce, hampering optimal treatment choices and subsequent patient outcomes. Here, we employed antifungal susceptibility testing (AFST) based on microbroth dilution on a set of 155 series Versicolores strains using the common antifungals amphotericin B, itraconazole, voriconazole, posaconazole, isavuconazole and micafungin with the addition of luliconazole and olorofim. All strains were identified using partial calmodulin gene sequencing, with 145 being A. sydowii, seven A. creber and three A. versicolor, using the latest taxonomic insights. Overall, tested antifungals were potent against the entire strain collection. In comparison to A. fumigatus, azole and amphotericin B MICs were slightly elevated for some strains. AFST with luliconazole and olorofim, here reported for the first time, displayed the highest in vitro activity, making these antifungals interesting alternative drugs but clinical studies are warranted for future therapeutic use.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11222195/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MycopathologiaPub Date : 2024-06-28DOI: 10.1007/s11046-024-00867-w
Flávio Guinsburg Hamburger, Ana Cristina Gales, Arnaldo Lopes Colombo
{"title":"Systematic Review of Candidemia in Brazil: Unlocking Historical Trends and Challenges in Conducting Surveys in Middle-Income Countries.","authors":"Flávio Guinsburg Hamburger, Ana Cristina Gales, Arnaldo Lopes Colombo","doi":"10.1007/s11046-024-00867-w","DOIUrl":"10.1007/s11046-024-00867-w","url":null,"abstract":"<p><strong>Introduction: </strong>Candidemia, a bloodstream infection predominantly affecting critically ill patients, poses a significant global health threat especially with the emergence of non-albicans Candida species, including drug-resistant strains. In Brazil, limited access to advanced diagnostic tools and trained microbiologists hampers accurate identification of Candida species and susceptibility to antifungals testing hindering surveillance efforts.</p><p><strong>Methods: </strong>We conducted a systematic review spanning publications from 2017 to 2023 addressing Candida species distribution and antifungal susceptibility among Brazilian patients with candidemia.</p><p><strong>Results: </strong>Despite initially identifying 7075 records, only 16 met inclusion criteria providing accurate information of 2305 episodes of candidemia. The predominant species were C. albicans, C. parapsilosis, and C. tropicalis, followed by notable proportions of Nakaseomyces glabratus. Limited access to diagnostic tests was evident as only 5 out of 16 studies on candidemia were able to report antifungal susceptibility testing results. In vitro resistance to echinocandins was rare (only 6/396 isolates, 1,5%). In counterpart, fluconazole exhibited resistance rates ranging from 0 to 43%, with great heterogeneity among different studies and species of Candida considered.</p><p><strong>Conclusion: </strong>Our review underscores the critical need for enhanced surveillance and research efforts to address the evolving landscape of candidemia and antifungal resistance in Brazil. Despite some limitations, available data suggest that while resistance to echinocandins and amphotericin B remains rare, there is a growing concern regarding resistance to fluconazole among Candida species.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MycopathologiaPub Date : 2024-06-18DOI: 10.1007/s11046-024-00843-4
Xiaoxi Xu, Junwen Huang, Li Luo, Yuping Ran
{"title":"A Giant Panda's Skin and Hairs Infection of Nannizzia Gypsum on Lumbosacral Region Successfully Treated by Oral Terbinafine and Topic Naftifine-ketoconazole Cream.","authors":"Xiaoxi Xu, Junwen Huang, Li Luo, Yuping Ran","doi":"10.1007/s11046-024-00843-4","DOIUrl":"10.1007/s11046-024-00843-4","url":null,"abstract":"","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Comparative Transcriptome Analysis of T. rubrum, T. mentagrophytes, and M. gypseum Dermatophyte Biofilms in Response to Photodynamic Therapy.","authors":"Borui Chen, Jinyan Zhang, Juanjuan Li, Yuwen Qian, Binbin Huang, Xiaomo Wu","doi":"10.1007/s11046-024-00865-y","DOIUrl":"10.1007/s11046-024-00865-y","url":null,"abstract":"<p><p>Dermatophyte biofilms frequently count for inadequate responses and resistance to standard antifungal treatments, resulting in refractory chronic onychomycosis infection. Although antimicrobial photodynamic therapy (aPDT) has clinically proven to exert significant antifungal effects or even capable of eradicating dermatophyte biofilms, considerably less is known about the molecular mechanisms underlying aPDT and the potential dysregulation of signaling networks that could antagonize its action. The aim of this study is to elucidate the molecular mechanisms underlining aPDT combat against dermatophyte biofilm in recalcitrant onychomycosis and to decipher the potential detoxification processes elicited by aPDT, facilitating the development of more effective photodynamic interventions. We applied genome-wide comparative transcriptome analysis to investigate how aPDT disrupting onychomycosis biofilm formed by three distinct dermatophytes, including Trichophyton rubrum, Trichophyton mentagrophytes, and Microsporum gypseum, the most frequently occurring pathogenic species. In total, 352.13 Gb of clean data were obtained for the transcriptomes of dermatophyte biofilms with or without aPDT treatment, resulting in 2,422.42 million reads with GC content of 51.84%, covering 99.9%, 98.5% and 99.4% of annotated genes of T. rubrum, T. mentagrophytes, and M. gypseum, respectively. The genome-wide orthologous analysis identified 6624 transcribed single-copy orthologous genes in all three species, and 36.5%, 6.8% and 17.9% of which were differentially expressed following aPDT treatment. Integrative orthology analysis demonstrated the upregulation of oxidoreductase activities is a highly conserved detoxification signaling alteration in response to aPDT across all investigated dermatophyte biofilms. This study provided new insights into the molecular mechanisms underneath anti-dermatophyte biofilm effects of aPDT and successfully identified a conserved detoxification regulation upon the aPDT application.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141419955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MycopathologiaPub Date : 2024-06-15DOI: 10.1007/s11046-024-00858-x
M-A Bovy, P Beckers, F Defawe, F Lifrange, J Cheret, M-P Hayette, N Layios
{"title":"Aspergillus fumigatus Postoperative Fasciitis and Peritonitis.","authors":"M-A Bovy, P Beckers, F Defawe, F Lifrange, J Cheret, M-P Hayette, N Layios","doi":"10.1007/s11046-024-00858-x","DOIUrl":"10.1007/s11046-024-00858-x","url":null,"abstract":"<p><p>A 67 year-old male was admitted in the ICU because of multi-organ failure due to sepsis secondary to Fournier's gangrene. He had sustained radical prostatectomy in the last 48 hours. Peritoneal fluid and fatty tissue biopsies grew Aspergillus Fumigatus without concomitant pulmonary involvement. Postoperative acquisition via exogenous and endogenous routes is discussed, as this nosocomial entity is very rarely reported apart from peritoneal dialysis, especially in non-immunosuppressed patients.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141327696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
MycopathologiaPub Date : 2024-06-13DOI: 10.1007/s11046-024-00864-z
Vera Portillo, Dionysios Neofytos
{"title":"An Update on Breakthrough Invasive Mold Infections.","authors":"Vera Portillo, Dionysios Neofytos","doi":"10.1007/s11046-024-00864-z","DOIUrl":"10.1007/s11046-024-00864-z","url":null,"abstract":"<p><p>The incidence of breakthrough mold infections (bIMI) has been increasing, due to routine administration of broad-spectrum antifungal prophylaxis and an increasing pool of high-risk patient populations, with fungi more challenging to treat, resulting in a sustained high mortality, despite progress in diagnostic and therapeutic options. Pharmacokinetics of antifungal drugs, fungal, and host, including genetic, factors play a role in the emergence of bIMI. Suggested therapeutic approaches have included change of antifungal class treatment, with amphotericin-B products predominating as first-line empirical treatment and switching from one broad-spectrum azole to another remaining the most frequently used treatment modalities. Future perspectives include determining individual susceptibility to IMI to tailor prophylaxis and treatment strategies, improved diagnostic tests, and the introduction of new antifungal agents that may reduce morbidity and mortality caused by bIMI.</p>","PeriodicalId":19017,"journal":{"name":"Mycopathologia","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11176211/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141311200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}