Pharmacogenomics of Antifungal Agents

Ashbee, H. Ruth; Gilleece, Maria

doi:10.1016/b978-0-12-386882-4.00038-4

Cited by 8 publications

(4 citation statements)

References 131 publications

(124 reference statements)

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“…For an instance, the polyene class of amphotericin B can disrupt fungal cell membranes via ergosterol binding, pore formation and leakage of cellular ions and eventually lead to fungal cell death. 35 On the other hand, azoles prevent the C14α demethylation of lanosterol in fungi, which in turn stops the formation of ergosterol in the fungal cell membrane. 36 Furthermore, echinocandins work by inhibiting the production of β-(1,3)- d -glucan, which is a component of the fungal cell wall.…”

Section: Discussionmentioning

confidence: 99%

Comparison of in vitro Susceptibilities of Talaromyces marneffei in Mold and Yeast Forms in Malaysia

Tan¹,

Shuhairi²,

Ginsapu³

et al. 2023

IDR

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Purpose This study was aimed to determine minimum inhibitory concentration (MIC) differences between yeast and mold forms of T. marneffei in Malaysia. Patients and Methods Ninety-seven clinical strains of T. marneffei were received from various Malaysian hospitals from the year 2020 until 2022. Their identities were determined using microscopic, macroscopic and molecular methods. Next, the susceptibility of yeast and mold forms of each isolate against amphotericin B, itraconazole, voriconazole, posaconazole, ketoconazole, isavuconazole, terbinafine, caspofungin and micafungin were tested according to the broth microdilution according to the Clinical and Laboratory Standards Institute (CLSI) M38 and M27 guidelines. The geometric means of minimal inhibitory concentration (GM MIC), MIC 50 , and MIC 90 were determined for each antifungal. Additionally, Wilcoxon signed-rank test was used to compare the significant difference of GM MICs for each antifungal, GM MIC, MIC 50 and MIC 90 for the combined nine antifungals against different growth forms of T. marneffei . The significance was set at p <0.05. Results Micafungin had the highest GM MIC, MIC 50 and MIC 90 for mold form of T. marneffei . For yeast form, amphotericin B achieved the highest GM MIC and MIC 50 while micafungin achieved the highest MIC 90 . However, the GM MIC, MIC 50 and MIC 90 of terbinafine and azole antifungals on T. marneffei were similar to each other, namely between 0.03 and 0.60µg/mL. The difference of GM MIC of all tested antifungals except caspofungin and micafungin was insignificant. Overall, GM MIC, MIC 50 and MIC 90 of the combined nine antifungals against two growth forms were insignificant. Conclusion The findings suggested either yeast or mold form can be used in the susceptibility testing of T. marneffei against amphotericin B, itraconazole, voriconazole, posaconazole, ketoconazole, isavuconazole and terbinafine.

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Section: Discussionmentioning

confidence: 99%

Comparison of in vitro Susceptibilities of Talaromyces marneffei in Mold and Yeast Forms in Malaysia

Tan¹,

Shuhairi²,

Ginsapu³

et al. 2023

IDR

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“…This process causes changes in cell permeability leading to metabolic degradation, and ultimately leads to cell death [15]. The polyene amphotericin B has an initial half-life of 10-24 h, but after chronic use can last up to 15 days [16]. Nystatin is limited to treatment of cutaneous, mucocutaneous, and gastrointestinal fungal infections due to its poor absorption following oral or topical use.…”

Section: Candida Tropicalis -mentioning

confidence: 99%

Review of Treatments for Oropharyngeal Fungal Infections in HIV/AIDS Patients

Tilly

Tharmalingam

2022

Microbiology Research

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HIV and AIDS patients are susceptible to opportunistic infections. Oral candidiasis or thrush is the primary manifestation of fungal infection in these patients. The primary objective of this literature review was to summarize established and novel treatment options for oropharyngeal fungal infections in HIV/AIDS patients. Azoles and polyenes are the two primary antifungal drug classes employed for the treatment of oral candidiasis. A literature review was conducted on Medline and Google Scholar in October of 2021 using the keywords “Oral”, “Fungal”, “HIV”, and “Treatment”. Included studies were clinical trials, meta-analyses, and randomized controlled trials. Twenty-one studies regarding azoles, polyenes, and novel treatments for oropharyngeal fungal infections in HIV/AIDS patients were examined in this review. The primary concern demonstrated from these studies is increased reports of resistance to antifungals, especially development of fluconazole resistance. Additionally, studies demonstrated that fluconazole had different relapse durations comparative to other medications, and that posaconazole could possibly act as an alternate form of treatment. Nystatin was indicated as a first-line therapy for thrush in multiple studies but could be upstaged by miconazole nitrate in resource-poor settings. Amphotericin B was an effective treatment option and was shown to be resilient in terms of fungal resistance, however potent adverse side effects were reported. Alternative treatments, such as immunoglobulin antibodies and lemon grass, revealed promising antifungal effects for immunocompromised individuals. Taken together, this review provides a thorough summary of treatment options of oropharyngeal fungal infections in HIV/AIDS patients.

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“…They are used as building blocks for polymer and rubber industries 9 and as precursors for active pharmaceutical ingredients. 10 Indeed, the production of the polyene moieties in a number of secondary metabolites involves UbiD decarboxylases. For example, production of the diene moiety in the polyketide tautomycetin by Streptomyces griseochromogenes is catalyzed by UbiD-like TtnD during the polyketide tailoring steps 11 (Figure 1B).…”

mentioning

confidence: 99%

“…The UbiD-product scope includes polyenes, a large group of compounds abundant in nature, exhibiting a wide range of biological activities and with various structures and properties. , Conjugated alkenes such as dienes and polyenes are naturally found in terpenes and unsaturated fatty acids steroids, in carotenes or as part of antibiotics. They are used as building blocks for polymer and rubber industries and as precursors for active pharmaceutical ingredients . Indeed, the production of the polyene moieties in a number of secondary metabolites involves UbiD decarboxylases.…”

mentioning

confidence: 99%

A Biological Route to Conjugated Alkenes: Microbial Production of Hepta-1,3,5-triene

et al. 2021

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Conjugated alkenes such as dienes and polyenes have a range of applications as pharmaceutical agents and valuable building blocks in the polymer industry. Development of a renewable route to these compounds provides an alternative to fossil fuel derived production. The enzyme family of the UbiD decarboxylases offers substantial scope for alkene production, readily converting poly unsaturated acids. However, biochemical pathways producing the required substrates are poorly characterized, and UbiD-application has hitherto been limited to biological styrene production. Herein, we present a proof-of-principle study for microbial production of polyenes using a bioinspired strategy employing a polyketide synthase (PKS) in combination with a UbiD-enzyme. Deconstructing a bacterial iterative type II PKS enabled repurposing the broad-spectrum antibiotic andrimid biosynthesis pathway to access the metabolic intermediate 2,4,6-octatrienoic acid, a valuable chemical for material and pharmaceutical industry. Combination with the fungal ferulic acid decarboxylase (Fdc1) led to a biocatalytic cascade-type reaction for the production of hepta-1,3,5-triene in vivo. Our approach provides a novel route to generate unsaturated hydrocarbons and related chemicals and provides a blue-print for future development and application.

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Pharmacogenomics of Antifungal Agents

Cited by 8 publications

References 131 publications

Comparison of in vitro Susceptibilities of Talaromyces marneffei in Mold and Yeast Forms in Malaysia

Comparison of in vitro Susceptibilities of Talaromyces marneffei in Mold and Yeast Forms in Malaysia

Review of Treatments for Oropharyngeal Fungal Infections in HIV/AIDS Patients

A Biological Route to Conjugated Alkenes: Microbial Production of Hepta-1,3,5-triene

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