Invasive Fungal Infections and Approaches to Their Diagnosis

Pfaller, Michael A.

doi:10.1016/bs.mim.2015.05.002

Cited by 10 publications

(8 citation statements)

References 324 publications

(757 reference statements)

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“…A. mycotoxinivorans has also been recognized as an emerging opportunistic yeast pathogen that causes infections in immunocompromised patients (do Espıŕito Santo et al, 2020). In this study, differences in pathogenic genetic basis between clinical and non-clinical strains of A. mycotoxinivorans seem small to nonexistent, which is consistent with the findings of Pfaller (2015), who reported that any fungus can cause infection in a sufficiently immunocompromised host. For example, although Saccharomyces cerevisiae has a well-documented history of safe use in food (Sewalt et al, 2016), its colonization of the human body, whether long-lasting or transient, may occasionally result in infections (Anoop et al, 2015).…”

Section: Discussionsupporting

confidence: 89%

Complete Genome Sequencing and Comparative Analysis of the Clinically-Derived Apiotrichum mycotoxinivorans Strain GMU1709

Peng

Liu

et al. 2022

Front. Cell. Infect. Microbiol.

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Over the past decade, Apiotrichum mycotoxinivorans has been recognized globally as a source of opportunistic infections. It is a yeast-like fungus, and its association as an uncommon pulmonary pathogen with cystic fibrosis patients has been previously reported. Immunocompromised patients are at the highest risk of A. mycotoxinivorans infections. Therefore, to investigate the genetic basis for the pathogenicity of A. mycotoxinivorans, we performed whole-genome sequencing and comparative genomic analysis of A. mycotoxinivorans GMU1709 that was isolated from sputum specimens of a pneumonia patient receiving cardiac repair surgery. The assembly of Oxford Nanopore reads from the GMU1709 strain and its subsequent correction using Illumina paired-end reads yielded a high-quality complete genome with a genome size of 30.5 Mb in length, which comprised six chromosomes and one mitochondrion. Subsequently, 8,066 protein-coding genes were predicted based on multiple pieces of evidence, including transcriptomes. Phylogenomic analysis indicated that A. mycotoxinivorans exhibited the closest evolutionary affinity to A. veenhuisii, and both the A. mycotoxinivorans strains and the formerly Trichosporon cutaneum ACCC 20271 strain occupied the same phylogenetic position. Further comparative analysis supported that the ACCC 20271 strain belonged to A. mycotoxinivorans. Comparisons of three A. mycotoxinivorans strains indicated that the differences between clinical and non-clinical strains in pathogenicity and drug resistance may be little or none. Based on the comparisons with strains of other species in the Trichosporonaceae family, we identified potential key genetic factors associated with A. mycotoxinivorans infection or pathogenicity. In addition, we also deduced that A. mycotoxinivorans had great potential to inactivate some antibiotics (e.g., tetracycline), which may affect the efficacy of these drugs in co-infection. In general, our analyses provide a better understanding of the classification and phylogeny of the Trichosporonaceae family, uncover the underlying genetic basis of A. mycotoxinivorans infections and associated drug resistance, and provide clues into potential targets for further research and the therapeutic intervention of infections.

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Section: Discussionsupporting

confidence: 89%

Complete Genome Sequencing and Comparative Analysis of the Clinically-Derived Apiotrichum mycotoxinivorans Strain GMU1709

Peng

Liu

et al. 2022

Front. Cell. Infect. Microbiol.

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“…The sequences of the 28S ribosomal DNA and ␤-tubulin genes of Aspergillus spp. were analyzed (47)(48)(49)(50).…”

Section: Methodsmentioning

confidence: 99%

Activity of a Long-Acting Echinocandin, Rezafungin, and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates (SENTRY Program, 2016 to 2018)

Pfaller

Carvalhaes

Messer

et al. 2020

Antimicrob Agents Chemother

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We evaluated the activity of rezafungin and comparators, using Clinical and Laboratory Standards Institute (CLSI) broth microdilution methods, against a worldwide collection of 2,205 invasive fungal isolates recovered from 2016 to 2018. Candida (n = 1,904 isolates; 6 species), Cryptococcus neoformans (n = 73), Aspergillus fumigatus (n = 183), and Aspergillus flavus (n = 45) isolates were tested for their susceptibility (S) to rezafungin as well as the comparators caspofungin, anidulafungin, micafungin, and azoles. Interpretive criteria were applied following CLSI published clinical breakpoints (CBPs) and epidemiological cutoff values (ECVs). Isolates displaying non-wild-type (non-WT) echinocandin MIC values were sequenced for hot spot (HS) mutations. Rezafungin inhibited 99.8% of Candida albicans isolates (MIC50/90, 0.03/0.06 μg/ml), 95.7% of Candida glabrata isolates (MIC50/90, 0.06/0.12 μg/ml), 97.4% of Candida tropicalis isolates (MIC50/90, 0.03/0.06 μg/ml), 100.0% of Candida krusei isolates (MIC50/90, 0.03/0.06 μg/ml), and 100.0% of Candida dubliniensis isolates (MIC50/90, 0.06/0.12 μg/ml) at ≤0.12 μg/ml. All (329/329 [100.0%]) Candida parapsilosis isolates (MIC50/90,1/2 μg/ml) were inhibited by rezafungin at ≤4 μg/ml. Fluconazole resistance was detected among 8.6% of C. glabrata isolates, 12.5% of C. parapsilosis isolates, 3.2% of C. dubliniensis isolates, and 2.6% of C. tropicalis isolates. The activity of rezafungin against these 6 Candida spp. was similar to the activity of the other echinocandins. Detection of the HS mutation was performed by sequencing echinocandin-resistant or non-WT Candida isolates. Good activity against C. neoformans was observed for fluconazole and the other azoles, whereas the echinocandins, including rezafungin, displayed limited activity. Rezafungin displayed activity similar to that of the other echinocandins against A. fumigatus and A. flavus. These in vitro data contribute to accumulating research demonstrating the potential of rezafungin for preventing and treating invasive fungal infections.

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“…Yeasts that were not identified by these methods were identified using sequencing-based methods involving the internal transcribed spacer (ITS) region, 28S ribosomal subunit, or intergenic spacer 1 (IGS1) (for Trichosporon spp.) (1,34,37,38).…”

Section: Organismsmentioning

confidence: 99%

“…), translation elongation factor (TEF) (for Fusarium spp. ), or the ITS (for all other species of filamentous fungi) (1,34,37,38).…”

Section: Organismsmentioning

confidence: 99%

In Vitro Activity of APX001A (Manogepix) and Comparator Agents against 1,706 Fungal Isolates Collected during an International Surveillance Program in 2017

Pfaller

Huband

Flamm

et al. 2019

Antimicrob Agents Chemother

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Current antifungal agents cover a majority of opportunistic fungal pathogens; however, breakthrough invasive fungal infections continue to occur and increasingly involve relatively uncommon yeasts and molds, which often exhibit decreased susceptibility. APX001A (manogepix) is a first-in-class small-molecule inhibitor of the conserved fungal Gwt1 protein. This enzyme is required for acylation of inositol during glycosylphosphatidylinositol anchor biosynthesis. APX001A is active against the major fungal pathogens, i.e., Candida (except Candida krusei), Aspergillus, and hardto-treat molds, including Fusarium and Scedosporium. In this study, we tested APX001A and comparators against 1,706 contemporary clinical fungal isolates collected in 2017 from 68 medical centers in North America (37.3%), Europe (43.4%), the Asia-Pacific region (12.7%), or Latin America (6.6%). Among the isolates tested, 78.5% were Candida spp., 3.9% were non-Candida yeasts, including 30 (1.8%) Cryptococcus neoformans var. grubii isolates, 14.7% were Aspergillus spp., and 2.9% were other molds. All isolates were tested by CLSI reference broth microdilution. APX001A (MIC 50 , 0.008 g/ml; MIC 90 , 0.06 g/ml) was the most active agent tested against Candida sp. isolates; corresponding anidulafungin, micafungin, and fluconazole MIC 90 values were 16-to 64-fold higher. Similarly, APX001A (MIC 50 , 0.25 g/ml; MIC 90 , 0.5 g/ml) was Ն8-fold more active than anidulafungin, micafungin, and fluconazole against C. neoformans var. grubii. Against Aspergillus spp., AXP001A (50% minimal effective concentration [MEC 50 ], 0.015 g/ml; MEC 90 , 0.03 g/ml) was comparable in activity to anidulafungin and micafungin. Aspergillus isolates (Ͼ98%) exhibited a wild-type phenotype for the mold-active triazoles (itraconazole, posaconazole, and voriconazole). APX001A was highly active against uncommon species of Candida, non-Candida yeasts, and rare molds, including 11 isolates of Scedosporium spp. (MEC values, 0.015 to 0.06 g/ml). APX001A demonstrated potent in vitro activity against recent fungal isolates, including echinocandin-and fluconazole-resistant strains. The extended spectrum of APX001A was also notable for its potency against many less common but antifungal-resistant strains. Further studies are in progress to evaluate the clinical utility of the methyl phosphate prodrug, APX001, in difficult-to-treat resistant fungal infections.

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Invasive Fungal Infections and Approaches to Their Diagnosis

Cited by 10 publications

References 324 publications

Complete Genome Sequencing and Comparative Analysis of the Clinically-Derived Apiotrichum mycotoxinivorans Strain GMU1709

Complete Genome Sequencing and Comparative Analysis of the Clinically-Derived Apiotrichum mycotoxinivorans Strain GMU1709

Activity of a Long-Acting Echinocandin, Rezafungin, and Comparator Antifungal Agents Tested against Contemporary Invasive Fungal Isolates (SENTRY Program, 2016 to 2018)

In Vitro Activity of APX001A (Manogepix) and Comparator Agents against 1,706 Fungal Isolates Collected during an International Surveillance Program in 2017

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