Whole genome sequencing of a clinical drug resistant Candida albicans isolate reveals known and novel mutations in genes involved in resistance acquisition mechanisms

Khalaf, Roy A.; Fattouh, Nour; Medvecký, Matej; Hrabák, Jaroslav

doi:10.1099/jmm.0.001351

Cited by 14 publications

(13 citation statements)

References 40 publications

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“…However, those mutations were also found in some susceptible isolates, and casual inferences could not be made. Polyene resistance has been linked to a reduction in the ergosterol content of the plasma membrane [51]. More research is needed to quantify membrane ergosterol levels and confirm the link between ergosterol content and resistance level.…”

Section: Discussionmentioning

confidence: 99%

Antifungal Susceptibility of Oral Candida Isolates From Mother-Infant Dyads to Nystatin, Fluconazole, and Caspofungin.

Alkhars¹,

Gaca²,

Zeng³

et al. 2023

Preprint

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The carriage of Candida albicans in children's oral cavities is associated with a higher risk for early childhood caries, so controlling this fungus in early life is essential for preventing caries. In a prospective cohort of 41 mothers and their children from 0-2 years of age, this study addressed 4 main objectives: 1) Evaluate in vitro the antifungal agent susceptibility of oral Candida isolates from the mother-child cohort, 2) Compare Candida susceptibility between isolates from the mothers and children; 3) Assess longitudinal changes in the susceptibility of the isolates collected between 0-2 years; and 4) Detect mutations in C. albicans antifungal resistance genes. Susceptibility to antifungal medications was tested by in vitro broth microdilution and expressed as minimal inhibitory concentration (MIC). C. albicans clinical isolates were sequenced by whole genome sequencing, and the genes related to antifungal resistance, ERG3, ERG11, CDR1, CDR2, MDR1, and FKS1, were assessed. Four Candida spp (n=126) were isolated: C. albicans, C. parapsilosis, C. dubliniensis, and C. lusitaniae. Caspofungin was the most active drug for oral Candida, followed by fluconazole and nystatin. Two missense mutations in the CDR2 gene were shared among C. albicans isolates resistant to nystatin. Most of the children’s C. albicans isolates had MIC values similar to those from their mothers, and 70% remained stable to antifungal medications from 0-2 years. For caspofungin, 29% of the children’s isolates showed an increase in MIC values from 0-2 years. Results of the longitudinal cohort indicated that clinically used oral nystatin was ineffective in reducing the carriage of C. albicans in children; novel antifungal regimens in infants are needed for better oral yeast control.

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Section: Discussionmentioning

confidence: 99%

Antifungal Susceptibility of Oral Candida Isolates From Mother-Infant Dyads to Nystatin, Fluconazole, and Caspofungin.

Alkhars¹,

Gaca²,

Zeng³

et al. 2023

Preprint

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“…Several mechanisms are responsible for altering the susceptibility of fungi to azole antifungal drugs; increased ergosterol content is one of them. Indeed, several clinically isolated azole-resistant pathogenic fungi displayed higher ergosterol contents than azole-susceptible strains [34][35][36]. In this context, we compared the ergosterol contents of M. restricta cells grown at pH 5.0 with those grown at pH 6.5.…”

Section: Altered Ergosterol Content Cell Membrane and Wall Thickness ...mentioning

confidence: 99%

The Interkingdom Interaction with Staphylococcus Influences the Antifungal Susceptibility of the Cutaneous Fungus Malassezia

Yang

Park

Kim

et al. 2022

J. Microbiol. Biotechnol.

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Analysis of the microbial community in the human body has revealed that fungi reside with other microbes, such as bacteria, protists, and viruses, within the community. This observation has led to several studies investigating the intra-or inter-kingdom interactions between microbial members influencing skin health and diseases [1][2][3]. For example, Pseudomonas aeruginosa and Aspergillus fumigatus often share the host niche, such as the airways of cystic fibrosis patients, and the interkingdom between the microorganisms is likely to occur within the same ecological site. In this scenario, P. aeruginosa produces metabolites, such as quorum sensing molecules and siderophores, that possess antifungal activity [4]. Furthermore, studies have reported the effect of bacteria on the antifungal susceptibility of pathogenic fungi. The interaction between Staphylococcus epidermidis and Candida albicans, co-colonizers of the skin, has also been investigated, especially in a mixed biofilm format. Fluconazole diffusion was retained, but no difference in susceptibility of C. albicans to the drug was observed in polymicrobial biofilms [5]. A direct influence of secreted enzymes, such as proteinase, from the major skinassociated fungus Malassezia on the biofilm formation of Staphylococcus aureus, a noteworthy skin opportunistic bacterial pathogen, was also demonstrated experimentally [6].Malassezia is a commensal fungus found on the skin surfaces of warm-blooded animals, including humans, and comprised of 18 species [7][8][9]. Several studies based on amplicon sequencing and metagenome analysis demonstrated that Malassezia is the most dominant genus in the human skin. This fungus has been associated with various skin diseases, such as seborrheic dermatitis, dandruff, and atopic dermatitis [10,11]. However, the roles of Malassezia in the skin must still be elucidated. Ketoconazole is an imidazole derivative and the most commonly used azole antifungal drug to treat Malassezia-associated skin diseases [12][13][14]. The mechanism of ketoconazole's action against pathogenic fungi includes inhibiting 14α-lanosterol demethylase, which is encoded by ERG11, and converting lanosterol to ergosterol in the ergosterol biosynthesis pathway for fungal membrane synthesis; this results in the accumulation of toxic sterols causing increased membrane stress and growth arrest [15,16]. Although the effectiveness of ketoconazole is well established, studies have reported that several fungal strains, including Malassezia, that have been isolated from clinical specimens were resistant to the drug [17][18][19]. InThe skin is a dynamic ecosystem on which diverse microbes reside. The interkingdom interaction between microbial species in the skin microbiota is thought to influence the health and disease of the skin although the roles of the intra-and interkingdom interactions remain to be elucidated. In this context, the interactions between Malassezia and Staphylococcus, the most dominant microorganisms in the skin microbiota, have gained attention. This...

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“…Candida albicans (ATCC MYA-2876) also known as SC5314 is a normal inhabitant of mucosal membranes in human, and also an etiological pathogen for infections of both skin and mucosa. Higher ability to form biofilms and tissue invasion contribute to the high virulence of Candida albicans (ATCC MYA-2876), the strain is also known to be susceptible to all antifungals [12].…”

Section: Introductionmentioning

confidence: 99%

Anticandidal Activity of Hydroalcoholic Extract of Phyllanthus niruri L. (Stone-Breaker)

Maia

Wijesinghe

Barbosa

et al. 2022

Braz. arch. biol. technol.

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Candida is becoming more resistant to conventional treatments, and causes persistent and severe infections. This study evaluates the antifungal and virulence activities of the hydroalcoholic extract of Phyllanthus niruri (HE-Pn) on Candida. HE-Pn was prepared by maceration technique. Chemical composition of HE-Pn was determined using Gas Chromatography-Mass Spectrometry (GS-MS). Antifungal screening was done using agar well diffusion. CLSI M27-A3 was used to determine the Minimum Inhibitory (MIC) and Fungicidal Concentrations (MFC). Effects of HE-Pn on adhesion and germ tube of C. albicans (ATCC MYA-2876) were determined using XTT assay and germ tube formation assay, respectively. Transmission Electron HIGHLIGHTS• Hydroalcoholic extract of Phyllanthus niruri (HE-Pn) demonstrates anti-Candida activity.• HE-Pn reduces the germ-tube formation and adhesion of Candida albicans.• HE-Pn causes cell wall detachment, cytoplasmic granulation, vacuolation and chromatin condensation.• HE-Pn shows no toxicity on human keratinocyte cell line.

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Whole genome sequencing of a clinical drug resistant Candida albicans isolate reveals known and novel mutations in genes involved in resistance acquisition mechanisms

Cited by 14 publications

References 40 publications

Antifungal Susceptibility of Oral Candida Isolates From Mother-Infant Dyads to Nystatin, Fluconazole, and Caspofungin.

Antifungal Susceptibility of Oral Candida Isolates From Mother-Infant Dyads to Nystatin, Fluconazole, and Caspofungin.

The Interkingdom Interaction with Staphylococcus Influences the Antifungal Susceptibility of the Cutaneous Fungus Malassezia

Anticandidal Activity of Hydroalcoholic Extract of Phyllanthus niruri L. (Stone-Breaker)

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