Novel Antifungal Agents and Their Activity against Aspergillus Species

Vahedi-Shahandashti, Roya; Lass‐Flörl, Cornelia

doi:10.3390/jof6040213

Cited by 22 publications

(12 citation statements)

References 157 publications

(124 reference statements)

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“…Finally, another interesting compound is ASP2397 (VL-2397), which is a novel natural antifungal compound currently in phase 2 clinical trial ( ClinicalTrials.gov Identifier: NCT03327727). ASP2397 is a cyclic hexapeptide siderophore with a similar structure than ferrichrome, which has a high affinity for iron ( 224 , 229 ). ASP2397 showed high antifungal activity against A. fumigatus , A. terreus and A. flavus .…”

Section: Advances In Therapeutic Strategies and Future Perspectivesmentioning

confidence: 99%

“…Newly developed drugs, as well as drugs currently in development, are listed on the Aspergillosis website. 1 Several of these have shown promising results and are being tested in phase 3 clinical trials ( 224 ). Olorofim (F901318, ClinicalTrials.gov Identifier: NCT05101187), from a new class of antifungal drugs called orotomides, is highly active against Aspergillus spp.…”

Section: Advances In Therapeutic Strategies and Future Perspectivesmentioning

confidence: 99%

“…It shows high in vitro and in vivo activity against Aspergillus spp. ( 224 , 226 ). Ibrexafungerp (SCY-078, MK-3118, ClinicalTrials.gov Identifier: NCT03059992) is a triterpenoid antifungal also inhibiting the biosynthesis of β-(1,3)-D-glucan ( 227 ).…”

Section: Advances In Therapeutic Strategies and Future Perspectivesmentioning

confidence: 99%

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Recent Advances in Fungal Infections: From Lung Ecology to Therapeutic Strategies With a Focus on Aspergillus spp.

et al. 2022

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Fungal infections are estimated to be the main cause of death for more than 1.5 million people worldwide annually. However, fungal pathogenicity has been largely neglected. This is notably the case for pulmonary fungal infections, which are difficult to diagnose and to treat. We are currently facing a global emergence of antifungal resistance, which decreases the chances of survival for affected patients. New therapeutic approaches are therefore needed to face these life-threatening fungal infections. In this review, we will provide a general overview on respiratory fungal infections, with a focus on fungi of the genus Aspergillus. Next, the immunological and microbiological mechanisms of fungal pathogenesis will be discussed. The role of the respiratory mycobiota and its interactions with the bacterial microbiota on lung fungal infections will be presented from an ecological perspective. Finally, we will focus on existing and future innovative approaches for the treatment of respiratory fungal infections.

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Section: Advances In Therapeutic Strategies and Future Perspectivesmentioning

confidence: 99%

Section: Advances In Therapeutic Strategies and Future Perspectivesmentioning

confidence: 99%

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Recent Advances in Fungal Infections: From Lung Ecology to Therapeutic Strategies With a Focus on Aspergillus spp.

et al. 2022

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“…Most of these azoles have a similar mechanism of action; affecting sterols in the plasma membrane by targeting the 14α lanosterol demethylase enzyme, thereby also targeting the CYP450 family. It should be noted that new antifungals are under development and target, for example, GPI-anchor biosynthesis or sphingolipid synthesis [ 127 ], as well as cell wall synthesis and remodeling [ 128 ]. As of 2009, azole resistance became more common as from 6 to 12.8% of patients in the Netherlands were found to have resistant isolates, yet these numbers may vary between countries [ 129 , 130 ].…”

Section: Current and Past Treatments For Aspergillosis And The Rising...mentioning

confidence: 99%

Novel Treatment Approach for Aspergilloses by Targeting Germination

Verburg

Neer

Duca

et al. 2022

JoF

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Germination of conidia is an essential process within the Aspergillus life cycle and plays a major role during the infection of hosts. Conidia are able to avoid detection by the majority of leukocytes when dormant. Germination can cause severe health problems, specifically in immunocompromised people. Aspergillosis is most often caused by Aspergillus fumigatus (A. fumigatus) and affects neutropenic patients, as well as people with cystic fibrosis (CF). These patients are often unable to effectively detect and clear the conidia or hyphae and can develop chronic non-invasive and/or invasive infections or allergic inflammatory responses. Current treatments with (tri)azoles can be very effective to combat a variety of fungal infections. However, resistance against current azoles has emerged and has been increasing since 1998. As a consequence, patients infected with resistant A. fumigatus have a reported mortality rate of 88% to 100%. Especially with the growing number of patients that harbor azole-resistant Aspergilli, novel antifungals could provide an alternative. Aspergilloses differ in defining characteristics, but germination of conidia is one of the few common denominators. By specifically targeting conidial germination with novel antifungals, early intervention might be possible. In this review, we propose several morphotypes to disrupt conidial germination, as well as potential targets. Hopefully, new antifungals against such targets could contribute to disturbing the ability of Aspergilli to germinate and grow, resulting in a decreased fungal burden on patients.

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“…Among human hosts infected with pathogenic Aspergillus , effective treatment often requires antifungal drugs such as itraconazole, voriconazole and amphotericin B [ 13 ]. Currently, voriconazole is the recommended first-line of treatment and prophylactic agent against invasive aspergillosis [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Current Practices for Reference Gene Selection in RT-qPCR of Aspergillus: Outlook and Recommendations for the Future

Archer

2021

Genes

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Aspergillus is a genus of filamentous fungi with vast geographic and ecological distributions. Species within this genus are clinically, agriculturally and biotechnologically relevant, leading to increasing interest in elucidating gene expression dynamics of key metabolic and physiological processes. Reverse-transcription quantitative Polymerase Chain Reaction (RT-qPCR) is a sensitive and specific method of quantifying gene expression. A crucial step for comparing RT-qPCR results between strains and experimental conditions is normalisation to experimentally validated reference gene(s). In this review, we provide a critical analysis of current reference gene selection and validation practices for RT-qPCR gene expression analyses of Aspergillus. Of 90 primary research articles obtained through our PubMed query, 17 experimentally validated the reference gene(s) used. Twenty reference genes were used across the 90 studies, with beta-tubulin being the most used reference gene, followed by actin, 18S rRNA and glyceraldehyde 3-phosphate dehydrogenase. Sixteen of the 90 studies used multiple reference genes for normalisation. Failing to experimentally validate the stability of reference genes can lead to conflicting results, as was the case for four studies. Overall, our review highlights the need to experimentally validate reference genes in RT-qPCR studies of Aspergillus.

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Novel Antifungal Agents and Their Activity against Aspergillus Species

Cited by 22 publications

References 157 publications

Recent Advances in Fungal Infections: From Lung Ecology to Therapeutic Strategies With a Focus on Aspergillus spp.

Recent Advances in Fungal Infections: From Lung Ecology to Therapeutic Strategies With a Focus on Aspergillus spp.

Novel Treatment Approach for Aspergilloses by Targeting Germination

Current Practices for Reference Gene Selection in RT-qPCR of Aspergillus: Outlook and Recommendations for the Future

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