Suspension of Arthroderma and Trichophyton species in RPMI-1640 medium provided long-term viability at room temperature

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Time-Kill Kinetics and In Vitro Antifungal Susceptibility of Non-fumigatus Aspergillus Species Isolated from Patients with Ocular Mycoses

Aspergillus species can cause ocular morbidity and blindness, and thus, appropriate antifungal therapy is needed. We investigated the in vitro activity of itraconazole, voriconazole, posaconazole, caspofungin, anidulafungin, and amphotericin B against 14 Aspergillus isolates obtained from patients with ocular mycoses, using the CLSI reference broth microdilution methodology. In addition, time-kill assays were performed, exposing each isolate separately to 1-, 4-, and 16-fold concentrations above the minimum inhibitory concentration (MIC) of each antifungal agent. A sigmoid maximum-effect (Emax) model was used to fit the time-kill curve data. The drug effect was further evaluated by measuring an increase/decrease in the killing rate of the tested isolates. The MICs of amphotericin B, itraconazole, voriconazole, and posaconazole were 0.5–1.0, 1.0, 0.5–1.0, and 0.25 µg/ml for A. brasiliensis, A. niger, and A. tubingensis isolates, respectively, and 2.0–4.0, 0.5, 1.0 for A. flavus, and 0.12–0.25 µg/ml for A. nomius isolates, respectively. A. calidoustus had the highest MIC range for the azoles (4.0–16.0 µg/ml) among all isolates tested. The minimum effective concentrations of caspofungin and anidulafungin were ≤0.03–0.5 µg/ml and ≤0.03 µg/ml for all isolates, respectively. Posaconazole demonstrated maximal killing rates (Emax = 0.63 h−1, r2 = 0.71) against 14 ocular Aspergillus isolates, followed by amphotericin B (Emax = 0.39 h−1, r2 = 0.87), voriconazole (Emax = 0.35 h−1, r2 = 0.098), and itraconazole (Emax = 0.01 h−1, r2 = 0.98). Overall, the antifungal susceptibility of the non-fumigatusAspergillus isolates tested was species and antifungal agent dependent. Analysis of the kinetic growth assays, along with consideration of the killing rates, revealed that posaconazole was the most effective antifungal against all of the isolates

MTL genotypes, phenotypic switching, and susceptibility profiles of Candida parapsilosis species group compared to Lodderomyces elongisporus

WOS: 000406853600148PubMed ID: 28771588Reference isolates of Candida parapsilosis (n = 8), Candida metapsilosis (n = 6), Candida orthopsilosis (n = 7), and Lodderomyces elongisporus (n = 11) were analyzed to gain insight into their pathobiology and virulence mechanisms. Initial evaluation using BBL Chromagar Candida medium misidentified L. elongisporus isolates as C. albicans. Polymerase chain reaction analysis of isolate MTL idiomorphs revealed that all C. parapsilosis isolates were MTLa homozygous and no MTL alpha 1, alpha 2, a1, or a2 gene was detected in L. elongisporus isolates. For C. orthopsilosis, two isolates were MTLa homozygous and five were MTL-heterozygous. Similarly, one C. metapsilosis isolate was MTLa homozygous whereas five were MTL-heterozygous. Isolate phenotypic switching analysis revealed potential phenotypic switching in the MTLa homozygous C. metapsilosis isolate, resulting in concomitant elongated cell formation. Minimum inhibitory concentrations of fluconazole (FLC) and FK506, alone or in combination, were determined by checkerboard assay, with data analyzed using the fractional inhibitory concentration index model. Synergistic or additive effects of these compounds were commonly observed in C. parapsilosis and L. elongisporus isolates. No killer activity was observed in the studied isolates, as determined phenotypically. No significant difference in virulence was seen for the four species in a Galleria mellonella model (P > 0.05). In conclusion, our results demonstrated phenotypic switching of C. metapsilosis CBS 2315 and that FLC and FK506 represent a promising drug combination against C. parapsilosis and L. elongisporus. The findings of the present study contribute to our understanding of the biology, diagnosis, and new possible treatments of the C. parapsilosis species group and L. elongisporus.NIH/NIAID [AI39115-19, R01 AI50113-13]This work was supported by NIH/NIAID R37 MERIT Award AI39115-19, and NIH/NIAID R01 AI50113-13 provided support to J.H

Worldwide emergence of fluconazole-resistant Candida parapsilosis: current framework and future research roadmap

Candida parapsilosis is one of the most commen causes of life-threatening candidaemia, particularly in premature neonates, individuals with cancer of the haematopoietic system, and recipients of organ transplants. Historically, drug-susceptible strains have been linked to clonal outbreaks. However, worldwide studies started since 2018 have reported severe outbreaks among adults caused by fluconazole-resistant strains. Outbreaks caused by fluconazoleresistant strains are associated with high mortality rates and can persist despite strict infection control strategies. The emergence of resistance threatens the efficacy of azoles, which is the most widely used class of antifungals and the only available oral treatment option for candidaemia. The fact that most patients infected with fluconazole-resistant strains are azole-naive underscores the high potential adaptability of fluconazole-resistant strains to diverse hosts, environmental niches, and reservoirs. Another concern is the multidrug-resistant and echinocandin-tolerant C parapsilosis isolates, which emerged in 2020. Raising awareness, establishing effective clinical interventions, and understanding the biology and pathogenesis of fluconazole-resistant C parapsilosis are urgently needed to improve treatment strategies and outcomes.CJN is a cofounder of BioSynesis, a company developing diagnostics and therapeutics for biofilm infections. MH reports grants and research funding from Astellas Pharma, Gilead Sciences, MSD, Pfizer, Euroimmun, F2G, Pulmocide, IMMY, Mundipharma, and Scynexis, outside the submitted work. TG acknowledges support from the Spanish Ministry of Science and Innovation (PID2021–126067NB-I00), cofounded by European Regional Development Fund, the Catalan Research Agency (AGAUR) SGR423, the European Union's Horizon 2020 research and innovation programme (ERC-2016–724173); the Gordon and Betty Moore Foundation (GBMF9742), the La Caixa foundation (LCF/PR/HR21/00737), and the Instituto de Salud Carlos III (IMPACT Grant IMP/00019, and CIBERINFEC CB21/13/00061- ISCIII-SGEFI/ERDF). BZ acknowledges support from the National Key Research and Development Program of China 2021YFA0911300. All other authors declare no competing interests.Peer Reviewed"Article signat per 15 autors/es: Farnaz Daneshnia, João N de Almeida Júnior, Prof Macit Ilkit, Lisa Lombardi, Austin M Perry, Marilyn Gao, Clarissa J Nobile, Matthias Egger, Prof David S Perlin, Bing Zhai, Prof Tobias M Hohl, Prof Toni Gabaldón, Prof Arnaldo Lopes Colombo, Prof Martin Hoenigl, Amir Arastehfar"Postprint (published version

Estimated burden of serious human fungal diseases in Turkey

Seyedmousavi, Seyedmojtaba/0000-0002-6194-7447; Denning, David/0000-0001-5626-2251; Hedayati, Mohammad T./0000-0001-6415-4648; Ilkit, Macit/0000-0002-1174-4182WOS: 000453770400004PubMed: 30107069The current number of fungal infections occurring each year in Turkey is unknown. We estimated the burden of serious human fungal diseases based on the population at risk, existing epidemiological data from 1920 to 2017 and modelling previously described by the LIFE program (). Among the population of Turkey (80.8 million in 2017), approximately 1 785 811 (2.21%) people are estimated to suffer from a serious fungal infection each year. the model used predicts high prevalences of allergic fungal rhinosinusitis episodes (312 994 cases) (392/100 000), of severe asthma with fungal sensitisation (42 989 cases) (53.20 cases/100 000 adults per year), of allergic bronchopulmonary aspergillosis (32 594 cases) (40.33/100 000), of fungal keratitis (26 671 cases) (33/100 000) and of chronic pulmonary aspergillosis (5890 cases) (7.29/100 000). the estimated annual incidence for invasive aspergillosis is lower (3911 cases) (4.84/100 000 annually). Among about 22.5 million women aged 15-50 years, recurrent vulvovaginal candidiasis is estimated to occur in 1 350 371 (3342/100 000) females. the burden of three superficial fungal infections was also estimated: tinea pedis (1.79 million), tinea capitis (43 900) and onychomycosis (1.73 million). Given that the modelling estimates reported in the current study might be substantially under- or overestimated, formal epidemiological and comprehensive surveillance studies are required to validate or modify these estimates

Species Distinction in the Trichophyton rubrum Complex

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Identification of The Mating Type (MTL) Genotypes of Clinical Candida parapsilosis Complex Species isolated from Blood Cultures

Amaç: Candida parapsilosis, sistemik kandidoz etkenleri arasında Candida albicans’tan sonra en sık rastlanan Candida türlerinden biridir. Candida türlerinde eşey tipinin belirlenmesi ve eşeyli üremenin gerçekleştirilmesi, eşey tipi (MTL) gen bölgesi kontrolünde gerçekleşir. Bu bölge, iki farklı eşey tipinde (a ve α) tamamen farklı dizilimlerde olup idiomorf olarak adlandırılır. MTLa idiomorfu a1 ve a2 transkripsiyon faktörlerini kodlarken, MTLα, α1 ve α2 proteinlerini kodlar. Bu genler haricinde her iki idiomorfta da eşeyli üreme ile ilgili işlevleri bilinmeyen PAB, OBP ve PIK genlerinin a ya da α versiyonları vardır. Candida parapsilosis ve yakın ilişkili Candida orthopsilosis ile Candida metapsilosis türlerinde ise, bugüne kadar eşeyli üreme döngüsüne bugüne kadar rastlanmamıştır. Gerçekleştirilen incelemelerde, C. orthopsilosis’in MTLa ve MTLα homozigot ve MTLa/MTLα heterozigot genotiplerini içeren karışık bir popülasyon yapısına sahip olduğu, C. metapsilosis izolatlarının çoğunluğunun ise MTLa/MTLα heterozigot olduğu belirlenmiştir. Buna karşılık, şimdiye kadar incelenen C. parapsilosis izolatlarının hepsinin tek bir eşey tipinde (MTLa) olduğu görülmüştür. Yöntem: Sunulan çalışmada, Türkiye kaynaklı C. parapsilosis kökenlerinin MTL genotiplerinin belirlenmesi amaçlanmış ve bu amaçla 167 kan izolatı incelendi. ITS bölgesinin PCR’da çoğaltılarak sekanslanması ile C. parapsilosis olarak identifikasye edilen izolatlar, MTLa1, MTLa2, MTLα1 ve MTLα2 genleri yönünden taranmıştır. Bulgular: PCR sonucunda yalnızca MTLa1 ve MTLa2 genlerine rastlanmıştır; dolayısı ile tüm izolatların MTLa genotipine sahip olduğu belirlenmiştir. Sonuç: Bulgular önceki çalışmalarla birlikte değerlendirildiğinde, C. parapsilosis’in MTLα eşey tipinin zaman içerisinde yok olduğu veya henüz araştırılmamış coğrafi bölgelerde varlığını sürdürecek şekilde seyrek olduğu sonucuna varılmıştır.Objective: Candida parapsilosis is one of the most common species after Candida albicans among the causative factors of systemic candidosis. In Candida species, determination of the cell identity and the sexual reproduction process take place under the control of the mating type (MTLα) locus. This region has completely different sequences in two different mating types (a and α) and is called an idiomorph. While the MTLa idiomorph encodes the transcription factors a1 and a2, MTLα encodes α1 and α2 proteins. Apart from these genes, both idiomorphs have a or α versions of PAB, OBP, and PIK genes, whose functions in sexual reproduction are unknown. On the other hand, up to now neither Candida parapsilosis nor the closely related species Candida orthopsilosis or Candida metapsilosis has been reported to have sexual cycles. While C. orthopsilosis was found to have a mixed population structure harboring MTLa and MTLα homozygous and MTLa/MTLα heterozygous genotypes in realized studies, the majority of C. metapsilosis isolates were MTLa/ MTLα heterozygotes. Nevertheless, all C. parapsilosis isolates analyzed were found to be of a single mating type (MTLa). Method: This study was aimed to determine the MTL genotypes of C. parapsilosis isolates of Turkey origin, and 167 blood isolates were used for this purpose. The isolates identified as C. parapsilosis by PCR-amplifying and sequencing the ITS region were screened for MTLa1, MTLa2, MTLα1 and MTLα2 genes. Results: Only MTLa1 and MTLa2 genes were detected in PCR; therefore, all isolates were determined to have the MTLa genotype. Conclusion: When the results are assessed with previous findings, it could be inferred that the MTLα mating type of C. parapsilosis has been lost or extremely rare in yet unanalyzed geographical regions

Antifungal susceptibility, genotyping, resistance mechanism, and clinical profile of <i>Candida tropicalis</i> blood isolates

Candida tropicalis is one of the major candidaemia agents, associated with the highest mortality rates among Candida species, and developing resistance to azoles. Little is known about the molecular mechanisms of azole resistance, genotypic diversity, and the clinical background of C. tropicalis infections. Consequently, this study was designed to address those questions. Sixty-four C. tropicalis bloodstream isolates from 62 patients from three cities in Iran (2014-2019) were analyzed. Strain identification, antifungal susceptibility testing, and genotypic diversity analysis were performed by MALDI-TOF MS, CLSI-M27 A3/S4 protocol, and amplified fragment length polymorphism (AFLP) fingerprinting, respectively. Genes related to drug resistance (ERG11, MRR1, TAC1, UPC2, and FKS1 hotspot9s) were sequenced. The overall mortality rate was 59.6% (37/62). Strains were resistant to micafungin [minimum inhibitory concentration (MIC) ≥1 μg/ml, 2/64], itraconazole (MIC &gt; 0.5 μg/ml, 2/64), fluconazole (FLZ; MIC ≥ 8 μg/ml, 4/64), and voriconazole (MIC ≥ 1 μg/ml, 7/64). Pan-azole and FLZ + VRZ resistance were observed in one and two isolates, respectively, while none of the patients were exposed to azoles. MRR1 (T255P, 647S), TAC1 (N164I, R47Q), and UPC2 (T241A, Q340H, T381S) mutations were exclusively identified in FLZ-resistant isolates. AFLP fingerprinting revealed five major and seven minor genotypes; genotype G4 was predominant in all centers. The increasing number of FLZ-R C. tropicalis blood isolates and acquiring FLZ-R in FLZ-naive patients limit the efficiency of FLZ, especially in developing countries. The high mortality rate warrants reaching a consensus regarding the nosocomial mode of C. tropicalis transmission