Echinocandins as Biotechnological Tools for Treating Candida auris Infections

Cândido, Elizabete de Souza; Affonseca, Flávia; Cardoso, Marlon Henrique; Franco, Octávio L.

doi:10.3390/jof6030185

Cited by 14 publications

(8 citation statements)

References 63 publications

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“…Although there are no susceptibility breakpoints for C. auris strains, 38 echinocandins are the first-line treatment. 39 However, antifungal susceptibility testing is still recommended for the optimal management of infections and outbreaks. 40 We reported for the first time an outbreak of C. auris in Algeria.…”

Section: Stainsmentioning

confidence: 99%

Emergence of Candida auris in intensive care units in Algeria

Zerrouki

Ibrahim

Rebiahi

et al. 2022

Mycoses

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Background Currently, Candida auris is among the most serious emerging pathogens that can be associated with nosocomial infections and outbreaks in intensive care units. Clinicians must be able to identify and manage it quickly. Objective Here, we report for the first time in Algeria seven cases of C. auris infection or colonisation. Methods and Results The strains were isolated from clinical sites including bronchial aspirates (n = 4), wound swabs (n = 1), urine sample (n = 1) and peritoneal fluid (n = 1), in patients admitted to the intensive care unit. Candida auris was identified both by MALDI‐TOF and by sequencing the ITS region and the D1/D2 domain. Antifungal susceptibility testing was performed using the E‐test method. Non‐wildtype susceptibility was observed for five strains against fluconazole, itraconazole, voriconazole and caspofungin. Genotyping showed the presence of four clades (I–IV) in one hospital. Conclusions Appropriate antifungal treatments with rapid and accurate microbial identification are the cornerstone for the management and control of C. auris infections.

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Section: Stainsmentioning

confidence: 99%

Emergence of Candida auris in intensive care units in Algeria

Zerrouki

Ibrahim

Rebiahi

et al. 2022

Mycoses

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“…Thus, a need exists for novel treatments that reveal potent activity against C. auris . Recently, therapies focused on echinocandins’ synergism with other antifungal drugs were widely explored, representing a novel possibility for the treatment of C. auris infections [ 77 ].…”

Section: Candida Auris and Treatment Failure Of Common Commercial Antifungal Drugsmentioning

confidence: 99%

Candida auris: A Quick Review on Identification, Current Treatments, and Challenges

Černáková

Roudbary

Brás

et al. 2021

IJMS

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Candida auris is a novel and major fungal pathogen that has triggered several outbreaks in the last decade. The few drugs available to treat fungal diseases, the fact that this yeast has a high rate of multidrug resistance and the occurrence of misleading identifications, and the ability of forming biofilms (naturally more resistant to drugs) has made treatments of C. auris infections highly difficult. This review intends to quickly illustrate the main issues in C. auris identification, available treatments and the associated mechanisms of resistance, and the novel and alternative treatment and drugs (natural and synthetic) that have been recently reported.

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“…Therefore, they exhibit pronounced activity against a broad range of Candida spp. and Asperillus spp., especially against azole-resistant strains [4][5][6][7]. To date, caspofungin, micafungin, and anidulafungin have been used as first-line drugs to treat invasive fungal infections [3,6,8,9].…”

Section: Introductionmentioning

confidence: 99%

Improving the production of the micafungin precursor FR901379 in an industrial production strain

et al. 2023

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Background Micafungin is an echinocandin-type antifungal agent used for the clinical treatment of invasive fungal infections. It is semisynthesized from the sulfonated lipohexapeptide FR901379, a nonribosomal peptide produced by the filamentous fungus Coleophoma empetri. However, the low fermentation efficiency of FR901379 increases the cost of micafungin production and hinders its widespread clinical application. Results Here, a highly efficient FR901379-producing strain was constructed via systems metabolic engineering in C. empetri MEFC09. First, the biosynthesis pathway of FR901379 was optimized by overexpressing the rate-limiting enzymes cytochrome P450 McfF and McfH, which successfully eliminated the accumulation of unwanted byproducts and increased the production of FR901379. Then, the functions of putative self-resistance genes encoding β-1,3-glucan synthase were evaluated in vivo. The deletion of CEfks1 affected growth and resulted in more spherical cells. Additionally, the transcriptional activator McfJ for the regulation of FR901379 biosynthesis was identified and applied in metabolic engineering. Overexpressing mcfJ markedly increased the production of FR901379 from 0.3 g/L to 1.3 g/L. Finally, the engineered strain coexpressing mcfJ, mcfF, and mcfH was constructed for additive effects, and the FR901379 titer reached 4.0 g/L under fed-batch conditions in a 5 L bioreactor. Conclusions This study represents a significant improvement for the production of FR901379 and provides guidance for the establishment of efficient fungal cell factories for other echinocandins.

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Echinocandins as Biotechnological Tools for Treating Candida auris Infections

Cited by 14 publications

References 63 publications

Emergence of Candida auris in intensive care units in Algeria

Emergence of Candida auris in intensive care units in Algeria

Candida auris: A Quick Review on Identification, Current Treatments, and Challenges

Improving the production of the micafungin precursor FR901379 in an industrial production strain

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