Echinocandins – structure, mechanism of action and use in antifungal therapy

Szymański, Mateusz; Chmielewska, Sandra; Czyżewska, Urszula; Malinowska, Marta; Tylicki, Adam

doi:10.1080/14756366.2022.2050224

Cited by 115 publications

(65 citation statements)

References 143 publications

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“…Next, we repeated the growth tests in the presence of caspofungin (CSF), an antifungal drug which inhibits the activity of β-1,3-glucan synthase (Szymanski et al , 2022). The individual Δmrn1 and Δnab6 strains grew normally, while inactivation of the CWI pathway (Δbck1 or Δslt2) gave a slight growth defect (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…For the same reason, the cell wall is an attractive target for antifungal drugs. The echinocandin family of compounds, including caspofungin, inhibits β-1,3 glucan synthase (Szymanski et al , 2022). Other antifungal compounds such as Congo Red and Calcofluor White seem to disrupt cell wall structure by binding chitin and β-glucan polymers (Elorza et al , 1983; Roncero & Duran, 1985).…”

Section: Introductionmentioning

confidence: 99%

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Posttranscriptional regulation of cell wall integrity in budding yeast

Bresson

Schepachev

Tollervey

2022

Preprint

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The fungal cell wall provides protection and structure, and is an important target for antifungal compounds. A MAP kinase cascade termed the cell wall integrity (CWI) pathway regulates transcriptional responses to cell wall damage. Here we describe a posttranscriptional pathway that plays an important complementary role. We discovered that the RNA-binding proteins (RBPs) Mrn1 and Nab6 specifically target the 3′ UTRs of a largely overlapping set of cell wall-related mRNAs. These mRNAs are downregulated in the absence of Nab6, indicating a function in target mRNA stabilization. Nab6 acts in parallel to CWI signaling to maintain appropriate expression of cell wall genes during stress. Cells lacking both pathways are hypersensitive to antifungal compounds targeting the cell wall. Deletion of MRN1 partially alleviates growth defects associated with ∆nab6 and Mrn1 has an opposing function in mRNA destabilization. Our results uncover a novel posttranscriptional pathway which mediates cellular resistance to antifungal compounds.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Posttranscriptional regulation of cell wall integrity in budding yeast

Bresson

Schepachev

Tollervey

2022

Preprint

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“…All echinocandins have high efficiency in invasive infections and an exceptional safety profile. A novel echinocandin rezafungin with once-weekly dosing and activity against Candida spp., including subsets of echinocandin-resistant Candida auris , has been recently developed and is currently in phase III trials [ 170 , 171 , 172 , 173 , 174 , 175 , 176 ]. Echinocandins demonstrate wide distribution in different organs and tissues, except the brain and eyes [ 52 , 177 ].…”

Section: Treatment Of Invasive Candidiasismentioning

confidence: 99%

Diagnosis and Treatment of Invasive Candidiasis

Barantsevich

2022

Antibiotics

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Candida species, belonging to commensal microbial communities in humans, cause opportunistic infections in individuals with impaired immunity. Pathogens encountered in more than 90% cases of invasive candidiasis include C. albicans, C. glabrata, C. krusei, C. tropicalis, and C. parapsilosis. The most frequently diagnosed invasive infection is candidemia. About 50% of candidemia cases result in deep-seated infection due to hematogenous spread. The sensitivity of blood cultures in autopsy-proven invasive candidiasis ranges from 21% to 71%. Non-cultural methods (beta-D-glucan, T2Candida assays), especially beta-D-glucan in combination with procalcitonin, appear promising in the exclusion of invasive candidiasis with high sensitivity (98%) and negative predictive value (95%). There is currently a clear deficiency in approved sensitive and precise diagnostic techniques. Omics technologies seem promising, though require further development and study. Therapeutic options for invasive candidiasis are generally limited to four classes of systemic antifungals (polyenes, antimetabolite 5-fluorocytosine, azoles, echinocandins) with the two latter being highly effective and well-tolerated and hence the most widely used. Principles and methods of treatment are discussed in this review. The emergence of pan-drug-resistant C. auris strains indicates an insufficient choice of available medications. Further surveillance, alongside the development of diagnostic and therapeutic methods, is essential.

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“…(3) 5-fluorocytosine, it inhibits fungal DNA synthesis by inhibiting thymidylate synthetase [ 12 , 20 ]. (4) There are also some echinocandin antifungal drugs (anidulafungin, micafungin, and caspofungin) [ 21 , 22 , 23 , 24 , 25 , 26 , 27 ]. The mechanisms of these bioactive compounds against C. albicans are mainly related to inhibition of biofilm formation, inhibition of virulence factors and destruction of cell wall integrity.…”

Section: Introductionmentioning

confidence: 99%

Biocontrol of Candida albicans by Antagonistic Microorganisms and Bioactive Compounds

Jin

Zhang

et al. 2022

Antibiotics

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Candida albicans is an endogenous opportunistic pathogenic fungus that is harmless when the host system remains stable. However, C. albicans could seriously threaten human life and health when the body’s immune function declines or the normal flora is out of balance. Due to the increasing resistance of candidiasis to existing drugs, it is important to find new strategies to help treat this type of systemic fungal disease. Biological control is considered as a promising strategy which is more friendly and safer. In this review, we compare the bacteriostatic behavior of different antagonistic microorganisms (bacteria and fungi) against C. albicans. In addition, natural products with unique structures have attracted researchers’ attention. Therefore, the bioactive nature products produced by different microorganisms and their possible inhibitory mechanisms are also reviewed. The application of biological control strategies and the discovery of new compounds with antifungal activity will reduce the resistance of C. albicans, thereby promoting the development of novel diverse antifungal drugs.

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Echinocandins – structure, mechanism of action and use in antifungal therapy

Cited by 115 publications

References 143 publications

Posttranscriptional regulation of cell wall integrity in budding yeast

Posttranscriptional regulation of cell wall integrity in budding yeast

Diagnosis and Treatment of Invasive Candidiasis

Biocontrol of Candida albicans by Antagonistic Microorganisms and Bioactive Compounds

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