Rapid evolution of an adaptive multicellular morphology of Candida auris during systemic infection

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: March 16, 2024

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

Language: Английский

---

Candida auris Outbreaks: Current Status and Future Perspectives

Microorganisms, Journal Year: 2024, Volume and Issue: 12(5), P. 927 - 927

Published: May 1, 2024

Candida auris has been identified by the World Health Organization (WHO) as a critical priority pathogen on its latest list of fungi. C. infections are reported in bloodstream and less commonly cerebrospinal fluid abdomen, with mortality rates that range between 30% 72%. However, no large-scale epidemiology studies have until now. The diagnosis can be challenging, particularly when employing conventional techniques. This impede early detection outbreaks implementation appropriate control measures. yeast easily spread patients healthcare settings through contaminated environments or equipment, where it survive for extended periods. Therefore, would desirable to screen colonisation. allow facilities identify disease take prevention It is frequently unsusceptible drugs, varying patterns resistance observed among clades geographical regions. review provides updates auris, including epidemiology, clinical characteristics, genomic analysis, evolution, colonisation, infection, identification, profiles, therapeutic options, prevention, control.

Language: Английский

---

The many faces of Candida auris: Phenotypic and strain variation in an emerging pathogen

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(3), P. e1012011 - e1012011

Published: March 1, 2024

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

Language: Английский

---

Candida auris -associated hospitalizations and outbreaks, China, 2018–2023

Emerging Microbes & Infections, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 18, 2024

The emerging human fungal pathogen Candida auris has become a serious threat to public health. This spread 10 provinces in China as of December 2023. Here we describe 312 C. auris-associated hospitalizations and 4 outbreaks healthcare settings from 2018 Three genetic clades have been identified during this period. Molecular epidemiological analyses indicate that introduced local transmission occurred multiple instances China. Most isolated (98.7%) exhibited resistance fluconazole, while only small subset strains were resistant amphotericin B (4.2%) caspofungin (2.2%).

Language: Английский

---

Whole genome sequencing analysis demonstrates therapy‐induced echinocandin resistance in Candida auris isolates

Mycoses, Journal Year: 2023, Volume and Issue: 66(12), P. 1079 - 1086

Published: Sept. 15, 2023

Candida auris is an emerging, multidrug-resistant yeast, causing outbreaks in healthcare facilities. Echinocandins are the antifungal drugs of choice to treat candidiasis, as they cause few side effects and resistance rarely found. Previously, immunocompromised patients from Kuwait with C. colonisation or infection were treated echinocandins, within days months, was reported urine isolates. To determine whether development echinocandin due independent introductions resistant strains resulted intra-patient development, whole genome sequencing (WGS) single-nucleotide polymorphism (SNP) analysis performed on susceptible (n = 26) echinocandin-resistant 6) isolates seven patients. WGS SNP identified three distinct clusters differing 17-127 SNPs two patients, remaining five respectively. Sequential had a maximum 11 differences over time period 1-10 months. The majority reduced susceptibility displayed unique FKS1 substitutions including novel FKS1M690V substitution, nearly all genetically related, ranging only six compared same patient. Resistant shared common FKS1S639F substitution; however, did not suggest source. These findings strongly indicate that induced during treatment. Future studies should such capable long-term colonisation, subsequent breakthrough have propensity cross-infect other remain viable for longer periods hospital environment.

Language: Английский

---

Candida auris Infection, a Rapidly Emerging Threat in the Neonatal Intensive Care Units: A Systematic Review

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(6), P. 1586 - 1586

Published: March 10, 2024

(1) Background: In recent years, a global epidemiological shift in candidemia has been observed, marked by the emergence of resistant non-albicans Candida species. auris, particular, become significant concern, causing infections both pediatric and adult populations within healthcare settings. Despite its widespread impact, there is limited understanding clinical course transmission dynamics neonatal systemic auris infections, hindering effective prevention management. This study focused on epidemiologic data, presentation, risk factors, outcome C. infection population. (2) Methods: A systematic review literature using PubMed Scopus databases until December 2023 was conducted. (3) Results: total 24 relevant studies were identified, encompassing 476 documented cases neonates. Prematurity emerged as primary factor, alongside parenteral nutrition, central line insertion, mechanical ventilation, prior broad-spectrum antibiotic use. The mortality rate reached approximately 42%, with therapeutic details sparingly reported 12% cases. Treatment strategies varied, amphotericin B predominantly used monotherapy, while combination antifungal agents 44% Notably, 97.4% exhibited fluconazole resistance, 67.1% showed resistance to B. Limited data available other agents. (4) Conclusions: rarity their occurrence necessitates comprehensive preparedness patient care. deeper pathogenesis crucial for developing control prevent caused this pathogen.

Language: Английский

---

Acquired amphotericin B resistance leads to fitness trade-offs that can be mitigated by compensatory evolution in Candida auris

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(12), P. 3304 - 3320

Published: Nov. 20, 2024

Language: Английский

---

Discovery of the sixthCandida aurisclade in Singapore

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Aug. 6, 2023

Summary Background The emerging fungal pathogen Candida auris poses a serious threat to global public health due its worldwide distribution, multidrug-resistance, high transmissibility, propensity cause outbreaks and mortality rates. We report three C. isolates detected in Singapore, which are genetically distinct from all known clades (I-V) represent new clade (Clade VI). Methods Three epidemiologically unlinked clinical belonging the potential were whole-genome sequenced phenotypically characterized. complete genomes of these compared representative clades. To provide context, 3,651 international sequences (WGS) NCBI database included high-resolution single nucleotide polymorphism (SNP) analysis. Antifungal resistance genes, mating type locus, chromosomal rearrangements characterized WGS data Clade VI isolates. further implemented Bayesian logistic regression models simulate automatic detection V as their became available. Findings separated by >36,000 SNPs existing These had opposite allele different when closest IV relatives. As proof-of-concept, our classification model was able flag outlier clade. Furthermore, an independent submission Bangladesh found belong this Interpretation discovery Singapore Bangladesh, showing close relationship members South America, highlights unknown genetic diversity origin , particularly under-resourced regions. Active surveillance settings, along with effective sequencing strategies downstream analysis, will be essential identification novel strains, tracking transmission, containment adverse impacts caused infections. Funding This work supported National Medical Research Council (NMRC) research training fellowship (MOH-FLWSHP19may-0005), NCRS Duke-NUS Academic Center Clinical Program grant (09/FY2022/P1/17-A32, GRDUKP003401), Genedant-GIS Innovation grant. context Evidence before study searched PubMed using search terms “ ” AND “clade”, for papers published between Jan 1, 2009, July 2023. retrieved 115 publications. 60 relevant publications identified. 28 studies analyzed discussed molecular epidemiology including description clades, either outbreak or settings. There 11 case reports cases that determination. Two focused on determination non-healthcare environments. Clade-specific characteristics described 14 studies. One applied machine learning drug but not Four potentially lineages, subclades, All one five (I-V). strains differed more than 35,000 SNPs, there clade-specific differences geographical phenotypic characteristics, antifungal susceptibility profile, potential, manifestations. Pathogen Detection system contained 4,506 ten (0·22%) submissions Southeast Asian countries 92 (2·04%) Asia Indian subcontinent, parts Indomalayan biogeographic realm. Added value best knowledge, we first group perform hybrid assemblies clade, is other SNPs. Whole-genome SNP analysis characterization suggest they previously unreported sixth major High-resolution database, generated final dataset consisting 6.6 million genome pairs, revealed six clusters representing (Indomalayan). In addition, demonstrate approach can used investigations soon become available, thus providing earliest possible alert threats. Implications available evidence Despite antimicrobial burden Asia, regions disproportionately underrepresented genomic multidrug-resistant pathogen. suggests yet-to-be-reported may circulating region. Given multidrug resistance, healthcare-associated infection outbreaks, associated mortality, active continued vigilance necessary.

Language: Английский

---

Current global status of Candida auris an emerging multidrug-resistant fungal pathogen: bibliometric analysis and network visualization

Brazilian Journal of Microbiology, Journal Year: 2024, Volume and Issue: 55(1), P. 391 - 402

Published: Jan. 23, 2024

Language: Английский

---

Native human and mouse skin infection models to study Candida auris-host interactions

Microbes and Infection, Journal Year: 2023, Volume and Issue: 26(1-2), P. 105234 - 105234

Published: Oct. 7, 2023

The World Health Organization (WHO) declared certain fungal pathogens as global health threats for the next decade. Candida auris (C. auris) is a newly emerging skin-tropic multidrug-resistant pathogen that can cause life-threatening infections of high mortality in hospitals and healthcare settings. Here, we address an unmet need present novel native ex vivo skin models, thus extending previous C. auris-host interaction studies. We exploit histology immunofluorescence analysis biopsies human adult fetal, well mouse origin infected with via distinct routes. demonstrate intact barrier efficiently protects from penetration invasion. Although readily grows on skin, it reach deeper layers only upon physical disruption by needling or through otherwise damaged skin. By contrast, not necessary Importantly, show undergoes morphogenetic changes penetration, acquires pseudohyphal growth phenotypes dermal layers. Taken together, this new model toolset yields insights into colonization, adhesion, invasion properties versus results form crucial basis future studies immune defense to colonizing pathogens, offer options testing action efficacy topical antimicrobial compound formulations.

Language: Английский

---