Azole resistance in<i>Candida albicans</i>from animals: Highlights on efflux pump activity and gene overexpression

Rocha, Marcos Fábio Gadelha; Bandeira, Silviane Praciano; Alencar, Lucas Pereira de; Melo, Luciana Magalhães; Sales, Juscelino Chaves; Paiva, Manoel de Araújo Neto; Teixeira, Carlos Eduardo Cordeiro; Castelo-Branco, Débora de Souza Collares Maia; Pereira-Neto, Waldemiro de Aquino; Cordeiro, Rossana de Aguiar; Sidrim, José Júlio Costa; Brilhante, Raimunda Sâmia Nogueira

doi:10.1111/myc.12611

Cited by 35 publications

(24 citation statements)

References 42 publications

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“…The efflux of drugs mediated by efflux pumps is an important mechanism of antifungal resistance employed by Candida spp (37, 56, 57). From six distinct drug efflux transporters produced by the analyzed organisms, two of them (Cdr1 and orf19.4780) were more abundant in the fluconazole-resistant C. auris strain (MMC1) than in the other strains.…”

Section: Discussionmentioning

confidence: 99%

Candida auris: multi-omics signature of an emerging and multidrug-resistant pathogen

Zamith-Miranda

Heyman

Cleare

et al. 2019

Preprint

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Candida auris is a recently described pathogenic fungus that is causing invasive 24 outbreaks on all continents. The fungus is of high concern given the numbers of multidrug-25 resistant strains that have been isolated in distinct sites across the globe. The fact that its 26 diagnosis is still problematic suggests that the spreading of the pathogen remains 27 underestimated. Notably, the molecular mechanisms of virulence and antifungal resistance 28 employed by this new species are largely unknown. In the present work, we compared two 29 clinical isolates of C. auris with distinct drug susceptibility profiles and a Candida albicans 30 reference strain using a multi-omics approach. Our results show that, despite the distinct 31 drug-resistance profile, both C. auris strains appear to be very similar, albeit with a few 32 notable differences. However, when compared to C. albicans both C. auris strains have 33 major differences regarding their carbon utilization and downstream lipid and protein 34 content, suggesting a multi-factorial mechanism of drug resistance. The molecular profile 35 displayed by C. auris helps to explain the antifungal resistance and virulence phenotypes of 36 this new emerging pathogen. 37Importance: Candida auris was firstly described in Japan in 2009 and has now been the 38 cause of significant outbreaks across the globe. The high number of isolates that are 39 resistant to one or more antifungals, as well as the high mortality rates from patients with 40 bloodstream infections, has caught the attention of the medical mycology, infectious 41 disease and public health communities to this pathogenic fungus. In the current work, we 42 performed a broad multi-omics approach on two clinical isolates isolated in New York, the 43 most affected area in the USA and found that the omic profile of C. auris differs 44 3 significantly from C. albicans. Besides our insights into C. auris carbon utilization and 45 lipid and protein content, we believe that the availability of these data will enhance our 46 ability to combat this rapidly emerging pathogenic yeast. 48Candida auris is an emerging pathogenic fungus that was firstly described in 2009 after 49 being isolated from the ear discharge of a patient in Tokyo, Japan (1). After the new species 50 identification, a study in South Korea reported a misidentified C. auris strain isolated in 51 1996, which then became the first known case of human C. auris infection (2). Despite the 52 fact that bloodstream infections are the main cause of mortality among Candida spp 53 infections, C. auris strains have been isolated from various sites such as respiratory tract, 54 bones, and central nervous system (3) as well as on a variety of abiotic surfaces (4), which 55 suggests a metabolic plasticity to survive in distinct environments. The reports of C. auris 56 outbreaks in all continents suggest that this pathogen is spreading rapidly across the globe 57 and many of the isolated strains are resistant to at least one class of antifungals, or even 58 multidrug-re...

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Section: Discussionmentioning

confidence: 99%

Candida auris: multi-omics signature of an emerging and multidrug-resistant pathogen

Zamith-Miranda

Heyman

Cleare

et al. 2019

Preprint

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“… 29 The activity of efflux pumps is widely described as the main cause of drug resistance in C. albicans , with an overexpression of CDR1 and CDR2 genes even after short exposure to antifungal drugs. 30 – 32 Therefore, this study also investigated the possible involvement of efflux pumps and the expression of the connected CDR1 and CDR2 genes after the treatment of Candida biofilms.…”

Section: Introductionmentioning

confidence: 99%

Efficiency of gold nanoparticles coated with the antimicrobial peptide indolicidin against biofilm formation and development of <em>Candida </em>spp. clinical isolates

Alteriis¹,

Maselli²,

Falanga³

et al. 2018

IDR

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BackgroundThis article examines the use of a novel nano-system, gold nanoparticles coated with indolicidin (AuNPs–indolicidin), against pathogenic Candida albicans biofilms. Candida species cause frequent infections owing to their ability to form biofilms, primarily on implant devices.Materials and methodsWe used an integrated approach, evaluating the effect of AuNPs-indolicidin on prevention and eradication of Candida biofilms formed in multi-well polystyrene plates, with relative gene expression assays. Four biofilm-associated genes (FG1, HWP1, ALS1 and ALS3, and CDR1 and CDR2) involved in efflux pump were analyzed using reverse transcription polymerase chain reaction.ResultsTreatment with the nano-complex significantly inhibits the capacity of C. albicans to form biofilms and impairs preformed mature biofilms. Treatment with AuNPs–indolicidin results in an increase in the kinetics of Rhodamine 6G efflux and a reduction in the expression of biofilm-related genes.ConclusionThese data provide a chance to develop novel therapies against nosocomially acquired refractory C. albicans biofilms.

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“…This enrichment was associated with both the increase in bfr1 + mRNA levels, and increased RNA PolII Ser5 enrichment. Overexpression of ATP-binding type cassette efflux transporters has been associated with increased tolerance of S. cerevisiae industrial strains to alkane biofuels and, more recently, to multi-drug resistance phenotypes in clinical isolates of Candida albicans, suggesting these transporters are key to the removal of toxic substances from the cell (Ling et al 2013;Kell et al 2015;Popp et al 2017;Rocha et al 2017).…”

Section: Discussionmentioning

confidence: 99%

Adaptation to Industrial Stressors Through Genomic and Transcriptional Plasticity in a Bioethanol Producing Fission Yeast Isolate

Vassiliadis

Wong²,

Blinco

et al. 2020

G3 Genes|Genomes|Genetics

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Schizosaccharomyces pombe is a model unicellular eukaryote with ties to the basic research, oenology and industrial biotechnology sectors. While most investigations into S. pombe cell biology utilize Leupold’s 972h- laboratory strain background, recent studies have described a wealth of genetic and phenotypic diversity within wild populations of S. pombe including stress resistance phenotypes which may be of interest to industry. Here we describe the genomic and transcriptomic characterization of Wilmar-P, an S. pombe isolate used for bioethanol production from sugarcane molasses at industrial scale. Novel sequences present in Wilmar-P but not in the laboratory S. pombe genome included multiple coding sequences with near-perfect nucleotide identity to Schizosaccharomyces octosporus sequences. Wilmar-P also contained a ∼100kb duplication in the right arm of chromosome III, a region harboring ght5+, the predominant hexose transporter encoding gene. Transcriptomic analysis of Wilmar-P grown in molasses revealed strong downregulation of core environmental stress response genes and upregulation of hexose transporters and drug efflux pumps compared to laboratory S. pombe. Finally, examination of the regulatory network of Scr1, which is involved in the regulation of several genes differentially expressed on molasses, revealed expanded binding of this transcription factor in Wilmar-P compared to laboratory S. pombe in the molasses condition. Together our results point to both genomic plasticity and transcriptomic adaptation as mechanisms driving phenotypic adaptation of Wilmar-P to the molasses environment and therefore adds to our understanding of genetic diversity within industrial fission yeast strains and the capacity of this strain for commercial scale bioethanol production.

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Azole resistance inCandida albicansfrom animals: Highlights on efflux pump activity and gene overexpression

Cited by 35 publications

References 42 publications

Candida auris: multi-omics signature of an emerging and multidrug-resistant pathogen

Candida auris: multi-omics signature of an emerging and multidrug-resistant pathogen

Efficiency of gold nanoparticles coated with the antimicrobial peptide indolicidin against biofilm formation and development of <em>Candida </em>spp. clinical isolates

Adaptation to Industrial Stressors Through Genomic and Transcriptional Plasticity in a Bioethanol Producing Fission Yeast Isolate

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