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1.
Emerg Infect Dis ; 30(13): S36-S40, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38561642

RESUMO

Candida auris is an emerging fungal pathogen that typically affects patients in healthcare settings. Data on C. auris cases in correctional facilities are limited but are needed to guide public health recommendations. We describe cases and challenges of providing care for 13 patients who were transferred to correctional facilities during January 2020-December 2022 after having a positive C. auris specimen. All patients had positive specimens identified while receiving inpatient care at healthcare facilities in geographic areas with high C. auris prevalence. Correctional facilities reported challenges managing patients and implementing prevention measures; those challenges varied by whether patients were housed in prison medical units or general population units. Although rarely reported, C. auris cases in persons who are incarcerated may occur, particularly in persons with known risk factors. Measures to manage cases and prevent C. auris spread in correctional facilities should address setting-specific challenges in healthcare and nonhealthcare correctional environments.


Assuntos
Candida , Candidíase , Humanos , Candidíase/microbiologia , Candida auris , Antifúngicos/uso terapêutico , Estabelecimentos Correcionais
2.
Mycopathologia ; 189(3): 35, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637433

RESUMO

Candida auris, an emerging and multidrug-resistant fungal pathogen, has led to numerous outbreaks in China. While the resistance mechanisms against azole and amphotericin B have been studied, the development of drug resistance in this pathogen remains poorly understood, particularly in in vivo-generated drug-resistant strains. This study employed pathogen whole-genome sequencing to investigate the epidemiology and drug-resistance mutations of C. auris using 16 strains isolated from two patients. Identification was conducted through Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and antimicrobial susceptibilities were assessed using broth microdilution and Sensititre YeastOne YO10. Whole-genome sequencing revealed that all isolates belonged to the South Asian lineage, displaying genetic heterogeneity. Despite low genetic variability among patient isolates, notable mutations were identified, including Y132F in ERG11 and A585S in TAC1b, likely linked to increased fluconazole resistance. Strains from patient B also carried F214L in TAC1b, resulting in a consistent voriconazole minimum inhibitory concentration of 4 µg/mL across all isolates. Furthermore, a novel frameshift mutation in the SNG1 gene was observed in amphotericin B-resistant isolates compared to susceptible ones. Our findings suggest the potential transmission of C. auris and emphasize the need to explore variations related to antifungal resistance. This involves analyzing genomic mutations and karyotypes, especially in vivo, to compare sensitive and resistant strains. Further monitoring and validation efforts are crucial for a comprehensive understanding of the mechanisms of drug resistance in C. auris.


Assuntos
Antifúngicos , Candidíase , Humanos , Antifúngicos/farmacologia , Candidíase/microbiologia , Candida auris , Candida , Anfotericina B/farmacologia , Farmacorresistência Fúngica/genética , Testes de Sensibilidade Microbiana
3.
Microb Genom ; 10(4)2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38630608

RESUMO

Fungal pathogens commonly originate from benign or non-pathogenic strains living in the natural environment. The recently emerged human pathogen, Candida auris, is one example of a fungus believed to have originated in the environment and recently transitioned into a clinical setting. To date, however, there is limited evidence about the origins of this species in the natural environment and when it began associating with humans. One approach to overcome this gap is to reconstruct phylogenetic relationships between (1) strains isolated from clinical and non-clinical environments and (2) between species known to cause disease in humans and benign environmental saprobes. C. auris belongs to the Candida/Clavispora clade, a diverse group of 45 yeast species including human pathogens and environmental saprobes. We present a phylogenomic analysis of the Candida/Clavispora clade aimed at understanding the ecological breadth and evolutionary relationships between an expanded sample of environmentally and clinically isolated yeasts. To build a robust framework for investigating these relationships, we developed a whole-genome sequence dataset of 108 isolates representing 18 species, including four newly sequenced species and 18 environmentally isolated strains. Our phylogeny, based on 619 orthologous genes, shows environmentally isolated species and strains interspersed with clinically isolated counterparts, suggesting that there have been many transitions between humans and the natural environment in this clade. Our findings highlight the breadth of environments these yeasts inhabit and imply that many clinically isolated yeasts in this clade could just as easily live outside the human body in diverse natural environments and vice versa.


Assuntos
Candida auris , Candidíase , Humanos , Filogenia , Candidíase/microbiologia , Candida/genética , Evolução Biológica
4.
Front Cell Infect Microbiol ; 14: 1389020, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38601736

RESUMO

Introduction: Invasive candidiasis is a global public health problem as it poses a significant threat in hospital-settings. The aim of this study was to evaluate C14R, an analog derived from peptide BP100, as a potential antimicrobial peptide against the prevalent opportunistic yeast Candida albicans and the emergent multidrug-resistant yeast Candida auris. Methods: Antifungal susceptibility testing of C14R against 99 C. albicans and 105 C. auris clinical isolates from Colombia, was determined by broth microdilution. Fluconazole was used as a control antifungal. The synergy between C14R and fluconazole was assessed in resistant isolates. Assays against fungal biofilm and growth curves were also carried out. Morphological alterations of yeast cell surface were evaluated by scanning electron microscopy. A permeability assay verified the pore-forming ability of C14R. Results: C. albicans and C. auris isolates had a geometric mean MIC against C14R of 4.42 µg/ml and 5.34 µg/ml, respectively. Notably, none of the isolates of any species exhibited growth at the highest evaluated peptide concentration (200 µg/ml). Synergistic effects were observed when combining the peptide and fluconazole. C14R affects biofilm and growth of C. albicans and C. auris. Cell membrane disruptions were observed in both species after treatment with the peptide. It was confirmed that C14R form pores in C. albicans' membrane. Discussion: C14R has a potent antifungal activity against a large set of clinical isolates of both C. albicans and C. auris, showing its capacity to disrupt Candida membranes. This antifungal activity remains consistent across isolates regardless of their clinical source. Furthermore, the absence of correlation between MICs to C14R and resistance to fluconazole indicates the peptide's potential effectiveness against fluconazole-resistant strains. Our results suggest the potential of C14R, a pore-forming peptide, as a treatment option for fungal infections, such as invasive candidiasis, including fluconazole and amphotericin B -resistant strains.


Assuntos
Antifúngicos , Candidíase Invasiva , Candidíase , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Candida albicans , Fluconazol/farmacologia , Fluconazol/uso terapêutico , Candida auris , Peptídeos/farmacologia , Testes de Sensibilidade Microbiana , Farmacorresistência Fúngica
5.
Photochem Photobiol Sci ; 23(4): 681-692, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38446403

RESUMO

In addition to the rising number of patients affected by viruses and bacteria, the number of fungal infections has also been rising over the years. Due to the increase in resistance to various antimycotics, investigations into further disinfection options are important. In this study, two yeasts (Candida auris and Saccharomyces cerevisiae) and a mold (Cladosporium cladosporioides) were irradiated at 365, 400, and 450 nm individually. The resulting log 1 reduction doses were determined and compared with other studies. Furthermore, fluorescence measurements of C. auris were performed to detect possible involved photosensitizers. A roughly exponential photoinactivation was observed for all three fungi and all irradiation wavelengths with higher D90 doses for longer wavelengths. The determined log 1 reduction doses of C. auris and S. cerevisiae converged with increasing wavelength. However, S. cerevisiae was more photosensitive than C. auris for all irradiation wavelengths and is therefore not a suitable C. auris surrogate for photoinactivation experiments. For the mold C. cladosporioides, much higher D90 doses were determined than for both yeasts. Concerning potential photosensitizers, flavins and various porphyrins were detected by fluorescence measurements. By excitation at 365 nm, another, so far unreported fluorophore and potential photosensitizer was also observed. Based on its fluorescence spectrum, we assume it to be thiamine.Graphic abstract.


Assuntos
Candida auris , Saccharomyces cerevisiae , Humanos , Fármacos Fotossensibilizantes/farmacologia , Luz , Raios Ultravioleta , Antifúngicos , Testes de Sensibilidade Microbiana
6.
Mycoses ; 67(4): e13723, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38551121

RESUMO

BACKGROUND: The emergence of the pathogenic yeast Candida auris is of global concern due to its ability to cause hospital outbreaks and develop resistance against all antifungal drug classes. Based on published data for baker's yeast Saccharomyces cerevisiae, sphingolipid biosynthesis, which is essential for maintaining membrane fluidity and formation of lipid rafts, could offer a target for additive treatment. METHODS: We analysed the susceptibility of C. auris to myriocin, which is an inhibitor of the de novo synthesis of sphingolipids in eukaryotic cells in comparison to other Candida species. In addition, we combined sublethal concentrations of myriocin with the antifungal drugs amphotericin B and fluconazole in E-tests. Consequently, the combinatory effects of myriocin and amphotericin B were examined in broth microdilution assays. RESULTS: Myriocin-mediated inhibition of the sphingolipid biosynthesis affected the growth of C. auris. Sublethal myriocin concentrations increased fungal susceptibility to amphotericin B. Isolates which are phenotypically resistant (≥2 mg/L) to amphotericin B became susceptible in presence of myriocin. However, addition of myriocin had only limited effects onto the susceptibility of C. auris against fluconazole. CONCLUSIONS: Our results show that inhibition of de novo sphingolipid biosynthesis increases the susceptibility of C. auris to amphotericin B. This may potentially enhance antifungal treatment options fighting this often resistant yeast pathogen.


Assuntos
Anfotericina B , Antifúngicos , Ácidos Graxos Monoinsaturados , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Anfotericina B/farmacologia , Fluconazol/farmacologia , Candida auris , Candida , Saccharomyces cerevisiae , Testes de Sensibilidade Microbiana , Esfingolipídeos/farmacologia
7.
FEMS Yeast Res ; 242024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38444195

RESUMO

In this study, we explored the sphingolipid (SL) landscape in Candida auris, which plays pivotal roles in fungal biology and drug susceptibility. The composition of SLs exhibited substantial variations at both the SL class and molecular species levels among clade isolates. Utilizing principal component analysis, we successfully differentiated the five clades based on their SL class composition. While phytoceramide (PCer) was uniformly the most abundant SL class in all the isolates, other classes showed significant variations. These variations were not limited to SL class level only as the proportion of different molecular species containing variable number of carbons in fatty acid chains also differed between the isolates. Also a comparative analysis revealed abundance of ceramides and glucosylceramides in fluconazole susceptible isolates. Furthermore, by comparing drug-resistant and susceptible isolates within clade IV, we uncovered significant intraclade differences in key SL classes such as high PCer and low long chain base (LCB) content in resistant strains, underscoring the impact of SL heterogeneity on drug resistance development in C. auris. These findings shed light on the multifaceted interplay between genomic diversity, SLs, and drug resistance in this emerging fungal pathogen.


Assuntos
Antifúngicos , Candida , Antifúngicos/farmacologia , Candida auris , Esfingolipídeos , Farmacorresistência Fúngica , Testes de Sensibilidade Microbiana
8.
mBio ; 15(4): e0014624, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38477572

RESUMO

The emergence and evolutionary path of Candida auris poses an intriguing scientific enigma. Its isolation from a pet dog's oral cavity in Kansas, reported by White et al. (T. C. White, B. D. Esquivel, E. M. Rouse Salcido, A. M. Schweiker, et al., mBio 15:e03080-23, 2024, https://doi.org/10.1128/mbio.03080-23), carries significant implications. This discovery intensifies concerns about its hypothetical capacity for zoonotic transmission, particularly considering the dog's extensive human contact and the absence of secondary animal/human cases in both animals and humans. The findings challenge established notions of C. auris transmissibility and underscore the need for further investigation into the transmission dynamics, especially zooanthroponotic pathways. It raises concerns about its adaptability in different hosts and environments, highlighting potential role of environmental and animal reservoirs in its dissemination. Critical points include the evolving thermal tolerance and the genetic divergence in the isolate. This case exemplifies the necessity for an integrated One Health approach, combining human, animal, and environmental health perspectives, to unravel the complexities of C. auris's emergence and behavior.


Assuntos
Candida , Candidíase , Cães , Humanos , Animais , Candida/genética , Candida/isolamento & purificação , Candidíase/veterinária , Candidíase/microbiologia , Candida auris , Kansas , Mudança Climática , Fungos , Zoonoses , Boca
9.
Nat Commun ; 15(1): 2381, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38493178

RESUMO

Candida auris has become a serious threat to public health. The mechanisms of how this fungal pathogen adapts to the mammalian host are poorly understood. Here we report the rapid evolution of an adaptive C. auris multicellular aggregative morphology in the murine host during systemic infection. C. auris aggregative cells accumulate in the brain and exhibit obvious advantages over the single-celled yeast-form cells during systemic infection. Genetic mutations, specifically de novo point mutations in genes associated with cell division or budding processes, underlie the rapid evolution of this aggregative phenotype. Most mutated C. auris genes are associated with the regulation of cell wall integrity, cytokinesis, cytoskeletal properties, and cellular polarization. Moreover, the multicellular aggregates are notably more recalcitrant to the host antimicrobial peptides LL-37 and PACAP relative to the single-celled yeast-form cells. Overall, to survive in the host, C. auris can rapidly evolve a multicellular aggregative morphology via genetic mutations.


Assuntos
Candidíase , Sepse , Animais , Camundongos , Candida/genética , Candidíase/microbiologia , Candida auris , Saccharomyces cerevisiae , Fenótipo , Antifúngicos , Testes de Sensibilidade Microbiana , Mamíferos
10.
Int J Mol Sci ; 25(5)2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38474027

RESUMO

Candida spp. periprosthetic joint infections are rare but difficult-to-treat events, with a slow onset, unspecific symptoms or signs, and a significant relapse risk. Treatment with antifungals meets with little success, whereas prosthesis removal improves the outcome. In fact, Candida spp. adhere to orthopedic devices and grow forming biofilms that contribute to the persistence of this infection and relapse, and there is insufficient evidence that the use of antifungals has additional benefits for anti-biofilm activity. To date, studies on the direct antifungal activity of silver against Candida spp. are still scanty. Additionally, polycaprolactone (PCL), either pure or blended with calcium phosphate, could be a good candidate for the design of 3D scaffolds as engineered bone graft substitutes. Thus, the present research aimed to assess the antifungal and anti-biofilm activity of PCL-based constructs by the addition of antimicrobials, for instance, silver, against C. albicans and C. auris. The appearance of an inhibition halo around silver-functionalized PCL scaffolds for both C. albicans and C. auris was revealed, and a significant decrease in both adherent and planktonic yeasts further demonstrated the release of Ag+ from the 3D constructs. Due to the combined antifungal, osteoproliferative, and biodegradable properties, PCL-based 3D scaffolds enriched with silver showed good potential for bone tissue engineering and offer a promising strategy as an ideal anti-adhesive and anti-biofilm tool for the reduction in prosthetic joints of infections caused by Candida spp. by using antimicrobial molecule-targeted delivery.


Assuntos
Candida albicans , Candidíase , Poliésteres , Antifúngicos/farmacologia , Candida auris , Prata , Candida , Candidíase/microbiologia , Biofilmes , Fosfatos de Cálcio , Recidiva , Testes de Sensibilidade Microbiana
11.
PLoS Pathog ; 20(3): e1012076, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38466738

RESUMO

Candida auris is a fungal pathogen of humans responsible for nosocomial infections with high mortality rates. High levels of resistance to antifungal drugs and environmental persistence mean these infections are difficult to treat and eradicate from a healthcare setting. Understanding the life cycle and the genetics of this fungus underpinning clinically relevant traits, such as antifungal resistance and virulence, is of the utmost importance to develop novel treatments and therapies. Epidemiological and genomic studies have identified five geographical clades (I-V), which display phenotypic and genomic differences. Aggregation of cells, a phenotype primarily of clade III strains, has been linked to reduced virulence in some infection models. The aggregation phenotype has thus been associated with conferring an advantage for (skin) colonisation rather than for systemic infection. However, strains with different clade affiliations were compared to infer the effects of different morphologies on virulence. This makes it difficult to distinguish morphology-dependent causes from clade-specific or even strain-specific genetic factors. Here, we identify two different types of aggregation: one induced by antifungal treatment which is a result of a cell separation defect; and a second which is controlled by growth conditions and only occurs in strains with the ability to aggregate. The latter aggregation type depends on an ALS-family adhesin which is differentially expressed during aggregation in an aggregative C. auris strain. Finally, we demonstrate that macrophages cannot clear aggregates, suggesting that aggregation might after all provide a benefit during systemic infection and could facilitate long-term persistence in the host.


Assuntos
Antifúngicos , Candida , Humanos , Antifúngicos/uso terapêutico , Candida/genética , Candida auris , Virulência , Farmacorresistência Fúngica , Adesinas Bacterianas/metabolismo , Testes de Sensibilidade Microbiana
12.
PLoS Pathog ; 20(3): e1012011, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38427609

RESUMO

Candida auris is an emerging fungal pathogen with unusual evolutionary history-there are multiple distinct phylogeographic clades showing a near simultaneous transition from a currently unknown reservoir to nosocomial pathogen. Each of these clades has experienced different selective pressures over time, likely resulting in selection for genotypes with differential fitness or phenotypic consequences when introduced to new environments. We also observe diversification within clades, providing additional opportunities for phenotypic differences. These differences can have large impacts on pathogenic potential, drug resistance profile, evolutionary trajectory, and transmissibility. In recent years, there have been significant advances in our understanding of strain-specific behavior in other microbes, including bacterial and fungal pathogens, and we have an opportunity to take this strain variation into account when describing aspects of C. auris biology. Here, we critically review the literature to gain insight into differences at both the strain and clade levels in C. auris, focusing on phenotypes associated with clinical disease or transmission. Our goal is to integrate clinical and epidemiological perspectives with molecular perspectives in a way that would be valuable for both audiences. Identifying differences between strains and understanding which phenotypes are strain specific will be crucial for understanding this emerging pathogen, and an important caveat when describing the analysis of a singular isolate.


Assuntos
Evolução Biológica , Candida auris , Fenótipo , Genótipo , Hospitais
13.
Emerg Microbes Infect ; 13(1): 2322649, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38431850

RESUMO

Candida auris has emerged as a problematic fungal pathogen associated with high morbidity and mortality. Amphotericin B (AmB) is the most effective antifungal used to treat invasive fungal candidiasis, with resistance rarely observed among clinical isolates. However, C. auris possesses extraordinary resistant profiles against all available antifungal drugs, including AmB. In our pursuit of potential solutions, we screened a panel of 727 FDA-approved drugs. We identified the proton pump inhibitor lansoprazole (LNP) as a potent enhancer of AmB's activity against C. auris. LNP also potentiates the antifungal activity of AmB against other medically important species of Candida and Cryptococcus. Our investigations into the mechanism of action unveiled that LNP metabolite(s) interact with a crucial target in the mitochondrial respiratory chain (complex III, known as cytochrome bc1). This interaction increases oxidative stress within fungal cells. Our results demonstrated the critical role of an active respiratory function in the antifungal activity of LNP. Most importantly, LNP restored the efficacy of AmB in an immunocompromised mouse model, resulting in a 1.7-log (∼98%) CFU reduction in the burden of C. auris in the kidneys. Our findings strongly advocate for a comprehensive evaluation of LNP as a cytochrome bc1 inhibitor for combating drug-resistant C. auris infections.


Assuntos
Anfotericina B , Antifúngicos , Candidíase , Animais , Camundongos , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Candida auris , Lansoprazol/farmacologia , Respiração , Citocromos
14.
J Clin Microbiol ; 62(4): e0152823, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38501836

RESUMO

Although the Vitek 2 system is broadly used for antifungal susceptibility testing of Candida spp., its performance against Candida auris has been assessed using limited number of isolates recovered from restricted geographic areas. We therefore compared Vitek 2 system with the reference Clinical and Laboratory Standards Institute (CLSI) broth microdilution method using an international collection of 100 C. auris isolates belonging to different clades. The agreement ±1 twofold dilution between the two methods and the categorical agreement (CA) based on the Centers for Disease Control and Prevention's (CDC's) tentative resistance breakpoints and Vitek 2-specific wild-type upper limit values (WT-ULVs) were determined. The CLSI-Vitek 2 agreement was poor for 5-flucytosine (0%), fluconazole (16%), and amphotericin B (29%), and moderate for voriconazole (61%), micafungin (67%), and caspofungin (81%). Significant interpretation errors were recorded using the CDC breakpoints for amphotericin B (31% CA, 69% major errors; MaEs) and fluconazole (69% CA, 31% very major errors; VmEs), but not for echinocandins (99% CA, 1% MaEs for both micafungin and caspofungin) for which the Vitek 2 allowed correct categorization of echinocandin-resistant FKS1 mutant isolates. Discrepancies were reduced when the Vitek 2 WT-ULV of 16 mg/L for amphotericin B (98% CA, 2% MaEs) and of 4 mg/L for fluconazole (96% CA, 1% MaEs, 3% VmEs) were used. In conclusion, the Vitek 2 system performed well for echinocandin susceptibility testing of C .auris. Resistance to fluconazole was underestimated whereas resistance to amphotericin B was overestimated using the CDC breakpoints of ≥32 and ≥2 mg/L, respectively. Vitek 2 minimun inhibitory concentrations (MICs) >4 mg/L indicated resistance to fluconazole and Vitek 2 MICs ≤16 mg/L indicated non-resistance to amphotericin B.


Assuntos
Anfotericina B , Fluconazol , Humanos , Fluconazol/farmacologia , Anfotericina B/farmacologia , Antifúngicos/farmacologia , Candida auris , Micafungina , Caspofungina , Testes de Sensibilidade Microbiana , Equinocandinas/farmacologia
15.
Microbiol Spectr ; 12(4): e0227823, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38440972

RESUMO

Candida auris is frequently associated with biofilm-related invasive infections. The resistant profile of these biofilms necessitates innovative therapeutic options, where quorum sensing may be a potential target. Farnesol and tyrosol are two fungal quorum-sensing molecules with antifungal effects at supraphysiological concentrations. Here, we performed genome-wide transcript profiling with C. auris biofilms following farnesol or tyrosol exposure using transcriptome sequencing (RNA-Seq). Since transition metals play a central role in fungal virulence and biofilm formation, levels of intracellular calcium, magnesium, and iron were determined following farnesol or tyrosol treatment using inductively coupled plasma optical emission spectrometry. Farnesol caused an 89.9% and 73.8% significant reduction in the calcium and magnesium content, respectively, whereas tyrosol resulted in 82.6%, 76.6%, and 81.2% decrease in the calcium, magnesium, and iron content, respectively, compared to the control. Genes involved in biofilm events, glycolysis, ergosterol biosynthesis, fatty acid oxidation, iron metabolism, and autophagy were primarily affected in treated cells. To prove ergosterol quorum-sensing molecule interactions, microdilution-based susceptibility testing was performed, where the complexation of farnesol, but not tyrosol, with ergosterol was impeded in the presence of exogenous ergosterol, resulting in a minimum inhibitory concentration increase in the quorum-sensing molecules. This study revealed several farnesol- and tyrosol-specific responses, which will contribute to the development of alternative therapies against C. auris biofilms. IMPORTANCE: Candida auris is a multidrug-resistant fungal pathogen, which is frequently associated with biofilm-related infections. Candida-derived quorum-sensing molecules (farnesol and tyrosol) play a pivotal role in the regulation of fungal morphogenesis and biofilm development. Furthermore, they may have remarkable anti-biofilm effects, especially at supraphysiological concentrations. Innovative therapeutic approaches interfering with quorum sensing may be a promising future strategy against C. auris biofilms; however, limited data are currently available concerning farnesol-induced and tyrosol-related molecular effects in C. auris. Here, we detected several genes involved in biofilm events, glycolysis, ergosterol biosynthesis, fatty acid oxidation, iron metabolism, and autophagy, which were primarily influenced following farnesol or tyrosol exposure. Moreover, calcium, magnesium, and iron homeostasis were also significantly affected. These results reveal those molecular and physiological events, which may support the development of novel therapeutic approaches against C. auris biofilms.


Assuntos
Candida auris , Farneseno Álcool , Álcool Feniletílico/análogos & derivados , Farneseno Álcool/farmacologia , Farneseno Álcool/metabolismo , Cálcio/metabolismo , Cálcio/farmacologia , Magnésio/metabolismo , Magnésio/farmacologia , Biofilmes , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Antifúngicos/metabolismo , Ergosterol , Ferro/metabolismo , Ácidos Graxos/metabolismo , Candida albicans , Testes de Sensibilidade Microbiana
17.
Med Mycol ; 62(3)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38414264

RESUMO

Candida auris poses threats to the global medical community due to its multidrug resistance, ability to cause nosocomial outbreaks and resistance to common sterilization agents. Different variants that emerged at different geographical zones were classified as clades. Clade-typing becomes necessary to track its spread, possible emergence of new clades, and to predict the properties that exhibit a clade bias. We previously reported a colony-Polymerase Chain Reaction-based, clade-identification method employing whole genome alignments and identification of clade-specific sequences of four major geographical clades. Here, we expand the panel by identifying clade 5 which was later isolated in Iran, using specific primers designed through in silico analyses.


Candida auris, a multidrug-resistant fungal pathogen, evolves as distinct geographical clades. We describe the identification of clade 5 specific DNA sequence, which was used to design primers that distinguished clade 5 from other clades, adding to the panel of the clade-identification system.


Assuntos
Candida , Candidíase , Animais , Candida/genética , Candidíase/epidemiologia , Candidíase/veterinária , Candida auris , Reação em Cadeia da Polimerase/veterinária , Genoma Fúngico , Antifúngicos/farmacologia , Testes de Sensibilidade Microbiana/veterinária
18.
Carbohydr Res ; 537: 109059, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38408423

RESUMO

Candida auris is an emerging fungal pathogen that has become a world-wide public health threat. While there have been numerous studies into the nature, composition and structure of the cell wall of Candida albicans and other Candida species, much less is known about the C. auris cell wall. We have shown that C. auris cell wall mannan contains a unique phosphomannan structure which distinguishes C. auris mannan from the mannans found in other fungal species. Specifically, C. auris exhibits two unique acid-labile mannose α-1-phosphate (Manα1PO4) sidechains that are absent in other fungal mannans and fungal pathogens. This unique mannan structural feature presents an opportunity for the development of vaccines, therapeutics, diagnostic tools and/or research reagents that target C. auris. Herein, we describe the successful synthesis and structural characterization of a Manα1PO4-containing disaccharide moiety that mimics the phosphomannan found in C. auris. Additionally, we present evidence that the synthetic Manα1PO4 glycomimetic is specifically recognized and bound by cell surface pattern recognition receptors, i.e. rhDectin-2, rhMannose receptor and rhMincle, that are known to play important roles in the innate immune response to C. auris as well as other fungal pathogens. The synthesis of the Manα1PO4 glycomimetic may represent an important starting point in the development of vaccines, therapeutics, diagnostics and research reagents which target a number of C. auris clinical strains. In addition, these data provide new insights and understanding into the structural biology of this unique fungal pathogen.


Assuntos
Mananas , Vacinas , Mananas/química , Candida auris , Manose , Candida albicans , Receptores de Superfície Celular , Parede Celular/química , Fosfatos
19.
mSphere ; 9(2): e0057723, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38299868

RESUMO

Since 2016, in Colombia, ongoing transmission of Candida auris has been reported in multiple cities. Here, we provide an updated description of C. auris genomic epidemiology and the dynamics of antifungal resistance in Colombia. We sequenced 99 isolates from C. auris cases with collection dates ranging from June 2016 to January 2021; the resulting sequences coupled with 103 previously generated sequences from C. auris cases were described in a phylogenetic analysis. All C. auris cases were clade IV. Of the 182 isolates with antifungal susceptibility data, 67 (37%) were resistant to fluconazole, and 39 (21%) were resistant to amphotericin B. Isolates predominately clustered by country except for 16 isolates from Bogotá, Colombia, which grouped with isolates from Venezuela. The largest cluster (N = 166 isolates) contained two subgroups. The first subgroup contained 26 isolates, mainly from César; of these, 85% (N = 22) were resistant to fluconazole. The second subgroup consisted of 47 isolates from the north coast; of these, 81% (N = 38) were resistant to amphotericin B. Mutations in the ERG11 and TAC1B genes were identified in fluconazole-resistant isolates. This work describes molecular mechanisms associated with C. auris antifungal resistance in Colombia. Overall, C. auris cases from different geographic locations in Colombia exhibited high genetic relatedness, suggesting continued transmission between cities since 2016. These findings also suggest a lack of or minimal introductions of different clades of C. auris into Colombia. IMPORTANCE: Candida auris is an emerging fungus that presents a serious global health threat and has caused multiple outbreaks in Colombia. This work discusses the likelihood of introductions and local transmission of C. auris and provides an updated description of the molecular mechanisms associated with antifungal resistance in Colombia. Efforts like this provide information about the evolving C. auris burden that could help guide public health strategies to control C. auris spread.


Assuntos
Antifúngicos , Candidíase , Humanos , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Anfotericina B , Candida auris , Fluconazol , Colômbia/epidemiologia , Candida/genética , Candidíase/microbiologia , Filogenia , Genômica
20.
Microbiol Spectr ; 12(4): e0356423, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38364098

RESUMO

CHROMagar Candida Plus is a new formulation of chromogenic media designed for the detection and differentiation of major clinical Candida species, including Candida auris. The objective of this study is to evaluate CHROMagar Candida Plus when used according to manufacturer's instructions with a panel of 206 fungal isolates and 83 skin-swab specimens originally collected for C. auris colonization screening. Of the 68 C. auris isolates tested, 66/68 displayed the expected light-blue colony morphology and blue halo within 48 h. None of the remaining 138 non-auris isolates appeared similar to C. auris. CHROMagarCandida Plus was, therefore, inclusive to 97% of 68 C. auris isolates tested and supported visual exclusion of 100% of the 138 non-C. auris isolates tested. For the 83 colonization screening specimens, direct plating onto CHROMagarCandida Plus was 60% sensitive and 100% specific when compared to the enrichment broth gold-standard reference method. In sum, these findings demonstrate the utility of this media when working with isolates but also notable limitations when working with primary skin-swabs specimens when competing yeast species are present.IMPORTANCECandida auris is an emerging fungal pathogen of public health concern. As it continues to spread, it is important to publish evaluations of new diagnostic tools. In this study, we share our experience with a new chromogenic media which can help distinguish C. auris from related species.


Assuntos
Candida , Candidíase , Humanos , Candida auris , Candidíase/diagnóstico , Candidíase/microbiologia , Meios de Cultura , Corantes , Antifúngicos
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