Candida auris is an emergent multidrug-resistant fungal pathogen considered a severe global threat due to its capacity to cause nosocomial outbreaks and deep-seated infections with high ...transmissibility and mortality. However, evidence on its pathogenicity and the complex host-pathogen interactions is still limited. This study used the
invertebrate model in Galleria mellonella to assess its virulence, exploring the mortality kinetics, melanization response, and morphological changes after fungal infection compared to Candida albicans and Candida parapsilosis, with known high and low pathogenicity, respectively. All C. auris isolates presented less virulence than C. albicans strains but higher than that induced by C. parapsilosis isolates. Increased pathogenicity was observed in nonaggregative phenotypes of C. auris, while the melanization response of the larvae to fungal infection was homogeneous and independent of the causing species. C. auris was able to filament in the
animal model G. mellonella, with aggregative and nonaggregative phenotypes presenting various pseudohyphal formation degrees as pathogenicity determinants in a strain-dependent manner. Histological invasiveness of C. auris mimicked that observed for C. albicans, with effective dissemination since the early stages of infection both in yeast and filamented forms, except for a remarkable respiratory tropism not previously observed in other yeasts. These characteristics widely differ between strains and advocate the hypothesis that the morphogenetic variability of C. auris is an indicator of its flexibility and adaptability, contributing to its emergence and rising worldwide prevalence.
Candida auris is an emergent fungus that has become a global threat due to its multidrug resistance, mortality, and transmissibility. These unique features make it different from other
species, but we still do not fully know the degree of virulence and, especially, the host-pathogen interactions. In this
insect model, we found that it presents an intermediate degree of virulence compared to known high- and low-virulence
species but with significant variability between aggregative and nonaggregative strains. Although it was previously considered unable to filament, we documented
filamentation as an important pathogenic determinant. We also found that it is able to disseminate early through the host, invading both the circulatory system and many different tissues with a remarkable respiratory tropism not previously described for other yeasts. Our study provides new insights into the pathogenicity of an emergent fungal pathogen and its interaction with the host and supports the hypothesis that its morphogenetic variability contributes to its rising global prevalence.
Candida auris has arisen as an important multidrug-resistant fungus because of several nosocomial outbreaks and elevated rates of mortality. Accurate and rapid diagnosis of C. auris is highly ...desired; nevertheless, current methods often present severe limitations and produce misidentification. Herein a sensitive, selective, and time-competitive biosensor based on oligonucleotide-gated nanomaterials for effective detection of C. auris is presented. In the proposed design, a nanoporous anodic alumina scaffold is filled with the fluorescent indicator rhodamine B and the pores blocked with different oligonucleotides capable of specifically recognize C. auris genomic DNA. Gate opening modulation and cargo delivery is controlled by successful DNA recognition. C. auris is detected at a concentration as low as 6 CFU/mL allowing obtaining a diagnostic result in clinical samples in one hour with no prior DNA extraction or amplification steps.
Candida auris has globally emerged as a multidrug-resistant fungus linked to healthcare-associated outbreaks. There is still limited evidence on its virulence, pathogenicity determinants, and complex ...host-pathogen interactions. This study analyzes the in vivo fungal behaviour, immune response, and host-pathogen interactions upon C. auris infection compared to C. albicans and C. parapsilosis in G. mellonella. This was performed by immunolabelling fungal structures and larval plasmatocytes and using a quantitative approach incorporating bioinformatic morphometric techniques into the study of microbial pathogenesis. C. auris presents a remarkably higher immunogenic activity than expected at its moderate degree of tissue invasion. It induces a greater inflammatory response than C. albicans and C. parapsilosis at the expense of plasmatocyte nodule formation, especially in non-aggregative strains. It specifically invades the larval respiratory system, in a pattern not previously observed in other Candida species, and presents inter-phenotypic tissue tropism differences. C. auris filaments in vivo less frequently than C. albicans or C. parapsilosis mostly through pseudohyphal growth. Filamentation might not be a major pathogenic determinant in C. auris, as less virulent aggregative phenotypes form pseudohyphae to a greater extent. C. auris has important both interspecific and intraspecific virulence and phenotype heterogeneity, with aggregative phenotypes of C. auris sharing characteristics with low pathogenic species such as C. parapsilosis. Our work suggests that C. auris owns an important morphogenetic plasticity that distinguishes it from other yeasts of the genus. Routine phenotypic identification of aggregative or non-aggregative phenotypes should be performed in the clinical setting as it may impact patient management.
A robust, sensitive, and time-competitive system to detect Candida albicans in less than 30 min in clinical samples based in capped nanoporous anodic alumina (NAA) is developed. In the proposed ...design, NAA pores are loaded with rhodamine B and then blocked with an oligonucleotide that is able to recognize C. albicans DNA. The capped material shows negligible cargo release, whereas dye delivery is selectively accomplished when genomic DNA from C. albicans is present. This procedure has been successfully applied to detect C. albicans in clinical samples from patients infected with this yeast. When compared with classical C. albicans detection methods, the proposed probe has a short assay time, high sensitivity and selectivity, demonstrating the high potential of this simple design for the diagnosis of infection produced by C. albicans.
Ibrexafungerp (SCY-078) is the newest oral and intravenous antifungal drug with broad activity, currently undergoing clinical trials for invasive candidiasis.
The aim of this study was to assess the
...activity of ibrexafungerp and comparators against a collection of 434 European blood isolates of
.
Ibrexafungerp, caspofungin, fluconazole, and micafungin minimum inhibitory concentrations (MICs) were collected from 12 European laboratories for 434 blood isolates, including 163
, 108
, 60
, 40
, 29
, 20
, 6
, 2
, 2
, and 1 isolate each of
,
, and
. MICs were determined by the EUCAST broth microdilution method, and isolates were classified according to recommended clinical breakpoints and epidemiological cutoffs. Additionally, 22
from different clinical specimens were evaluated.
Ibrexafungerp MICs ranged from 0.016 to ≥8 mg/L. The lowest ibrexafungerp MICs were observed for
(geometric MIC 0.062 mg/L, MIC range 0.016-0.5 mg/L) and the highest ibrexafungerp MICs were observed for
(geometric MIC 0.517 mg/L, MIC range 0.06-≥8 mg/L). Modal MICs/MIC
s (mg/L) against
spp. were 0.125/0.06 for
, 0.5/0.5 for
, 0.25/0.25 for
, 0.5/0.5 for
, 1/1 for
, 4/2 for
, and 0.5/0.5 for
. Ibrexafungerp showed activity against fluconazole- and echinocandin-resistant isolates. If adopting wild-type upper limits, a non-wild-type phenotype for ibrexafungerp was only observed for 16/434 (3.7%) isolates: 11 (4.6%)
, 4 (5%)
, and 1 (2.5%)
.
Ibrexafungerp showed a potent
activity against
.
Cetaceans, which are crucial in marine ecosystems, act as sentinels for ecosystem and human–environmental health. However, emerging fungal infections, particularly by Candida spp., pose a growing ...concern in these marine mammals. This review consolidates current knowledge on the prevalence, clinical manifestations, species distribution, and antifungal resistance of Candida infections in cetaceans. We detail the diverse pathogenic impacts of Candida, including respiratory, dermal, and systemic afflictions, underscoring diagnostic and treatment challenges amid rising antifungal resistance. Our analysis extends beyond health concerns in captive cetaceans, where confinement stress heightens vulnerability, to encompass substantial ecological risks in wild populations. The review emphasizes the One Health perspective, linking cetacean health with broader environmental and human public health issues. We particularly focus on the potential zoonotic transmission of emerging fungal pathogens such as Candida auris and the role of environmental changes in fostering antifungal resistance. The study underscores the need for concerted, interdisciplinary efforts in veterinary, medical, and environmental sciences to enhance understanding and management of Candida infections in cetaceans. We advocate for comprehensive monitoring and collaborative research initiatives to mitigate the rising challenge of these infections. Addressing Candida spp. in cetaceans is not just a conservation priority but a critical step in safeguarding overall marine health and, by extension, human health in the context of evolving infectious diseases.
The objectives of this study were to gain further insight on
genotype distribution and percentage of clustered isolates between hospitals and to identify potential clusters involving different ...hospitals and cities. We aim to genotype
spp. isolates causing candidemia in patients admitted to 16 hospitals in Spain, Italy, Denmark, and Brazil. Eight hundred and eighty-four isolates (
= 534;
= 282; and
= 68) were genotyped using species-specific microsatellite markers. CDC3, EF3, HIS3, CAI, CAIII, and CAVI were used for
, Ctrm1, Ctrm10, Ctrm12, Ctrm21, Ctrm24, and Ctrm28 for
, and CP1, CP4a, CP6, and B for
. Genotypes were classified as singletons (genotype only found once) or clusters (same genotype infecting two or more patients). Clusters were defined as intra-hospital (involving patients admitted to a single hospital), intra-ward (involving patients admitted to the same hospital ward) or widespread (involving patients admitted to different hospitals). The percentage of clusters and the proportion of patients involved in clusters among species, genotypic diversity and distribution of genetic diversity were assessed. Seven hundred and twenty-three genotypes were detected, 78 (11%) being clusters, most of which (57.7%;
= 45/78) were intra-hospital clusters including intra-ward ones (42.2%;
= 19/45). The proportion of clusters was not statistically different between species, but the percentage of patients in clusters varied among hospitals. A number of genotypes (7.2%; 52/723) were widespread (found at different hospitals), comprising 66.7% (52/78) of clusters, and involved patients at hospitals in the same city (
= 21) or in different cities (
= 31). Only one
cluster was a widespread genotype found in all four countries. Around 11% of
and
isolates causing candidemia are clusters that may result from patient-to-patient transmission, widespread genotypes commonly found in unrelated patients, or insufficient microsatellite typing genetic discrimination.
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