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1.
Front Cell Infect Microbiol ; 14: 1295841, 2024.
Article in English | MEDLINE | ID: mdl-38707510

ABSTRACT

Introduction: Although the existence of Candida species in the respiratory tract is often considered commensal, it is crucial to recognize the significance of Candida colonization in immunocompromised or COVID-19 patients. The emergence of Candida auris as an emerging pathogen further emphasizes the importance of monitoring yeast infection/colonization, particularly in COVID-19 patients. Methods: In this study, respiratory samples mainly from COVID-19 patients, primarily those suspected of having a fungal infection, were cultured on Sabouraud dextrose agar plates and the yeast colonies were identified using a two-step multiplex PCR method. The samples suspected of C. auris underwent specific nested PCR followed by sequence analysis. Results: A total of 199 respiratory samples were collected from 73 women and 126 men, ranging in age from 1.6 to 88 years. Among the patients, 141 had COVID-19, 32 had cancer, 5 were hospitalized in ICU, 2 had chronic obstructive pulmonary disease)COPD(, and others were patients with combination diseases. From these samples, a total of 334 yeast strains were identified. C. albicans (n=132, 39.52%) was the most common species, followed by C. tropicalis (n=67, 20%), C. glabrata (n=56, 16.76%), C. krusei (n=18, 5.4%), C. parapsilosis (n=17, 5.08%), Saccharomyces cerevisiae (n=10, 3%), C. kefyr (n=9, 2.6%), C. dubliniensis (n=7, 2.1%), C. lusitaniae (n=5, 1.5%), C. auris (n=3, 0.9%), C. guilliermondii (n=2, 0.6%), C. rugosa (n=1, 0.3%), C. intermedia (n=1, 0.3%), and Trichosporon spp. (n=1, 0.3%). C. auris was detected in a patient in ICU and two COVID-19 patients. While its presence was confirmed through sequence analysis, our extensive efforts to isolate C. auris were unsuccessful. Conclusion: While C. albicans colonization remains prevalent, our study found no evidence of Candida lung infection. Since the role of Candida colonization in airway secretions remains ambiguous due to limited research, further studies are imperative to shed light on this matter.


Subject(s)
COVID-19 , Candida auris , Candidiasis , SARS-CoV-2 , Humans , COVID-19/microbiology , Aged , Middle Aged , Female , Male , Aged, 80 and over , Adult , Child, Preschool , Candidiasis/microbiology , Child , Adolescent , Young Adult , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Infant , Candida auris/genetics , Candida auris/isolation & purification , Candida/isolation & purification , Candida/classification , Candida/genetics , Respiratory System/microbiology , Respiratory System/virology , Multiplex Polymerase Chain Reaction
2.
J Med Microbiol ; 73(5)2024 May.
Article in English | MEDLINE | ID: mdl-38771623

ABSTRACT

The emergent fungal pathogen Candida auris is increasingly recognised as an important cause of healthcare-associated infections globally. It is highly transmissible, adaptable, and persistent, resulting in an organism with significant outbreak potential that risks devastating consequences. Progress in the ability to identify C. auris in clinical specimens is encouraging, but laboratory diagnostic capacity and surveillance systems are lacking in many countries. Intrinsic resistance to commonly used antifungals, combined with the ability to rapidly acquire resistance to therapy, substantially restricts treatment options and novel agents are desperately needed. Despite this, outbreaks can be interrupted, and mortality avoided or minimised, through the application of rigorous infection prevention and control measures with an increasing evidence base. This review provides an update on epidemiology, the impact of the COVID-19 pandemic, risk factors, identification and typing, resistance profiles, treatment, detection of colonisation, and infection prevention and control measures for C. auris. This review has informed a planned 2024 update to the United Kingdom Health Security Agency (UKHSA) guidance on the laboratory investigation, management, and infection prevention and control of Candida auris. A multidisciplinary response is needed to control C. auris transmission in a healthcare setting and should emphasise outbreak preparedness and response, rapid contact tracing and isolation or cohorting of patients and staff, strict hand hygiene and other infection prevention and control measures, dedicated or single-use equipment, appropriate disinfection, and effective communication concerning patient transfers and discharge.


Subject(s)
Antifungal Agents , COVID-19 , Candida auris , Candidiasis , Infection Control , Humans , Candidiasis/prevention & control , Candidiasis/epidemiology , Candidiasis/drug therapy , Candidiasis/microbiology , Infection Control/methods , Candida auris/drug effects , COVID-19/prevention & control , COVID-19/epidemiology , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , England/epidemiology , Cross Infection/prevention & control , Cross Infection/epidemiology , Cross Infection/microbiology , SARS-CoV-2 , Drug Resistance, Fungal , Candida/drug effects , Candida/classification , Candida/isolation & purification , Disease Outbreaks/prevention & control
3.
PLoS One ; 19(5): e0302629, 2024.
Article in English | MEDLINE | ID: mdl-38781160

ABSTRACT

BACKGROUND: We investigated the spectrum of infection and risk factors for invasive fungal disease due to Candida auris (CA) in Qatar. METHODS: We performed structured chart reviews on individuals with any positive CA culture between May 2019 and December 2022 at three tertiary care hospitals in Qatar. Invasive CA disease (ICAD) was defined as a positive sterile site culture, or any positive culture for CA with appropriate antifungal prescription. Main outcomes included proportion of individuals who developed ICAD among those with positive cultures, and 30-day/in-hospital mortality. RESULTS: Among 331 eligible individuals, median age was 56 years, 83.1% were male, 70.7% were non-Qataris, and 37.5% had ≥ 3 comorbidities at baseline. Overall, 86.4% were deemed to have colonization and 13.6% developed ICAD. Those with ICAD were more likely to have invasive central venous or urinary catheterization and mechanical ventilation. Individuals with ICAD had longer prior ICU stay (16 vs 26 days, P = 0.002), and longer hospital length of stay (63 vs. 43 days; P = 0.003), and higher 30-day mortality (38% vs. 14%; P<0.001). In multivariable regression analysis, only mechanical ventilation was associated with a higher risk of ICAD (OR 3.33, 95% CI 1.09-10.17). CONCLUSION: Invasive Candida auris Disease is associated with longer hospital stay and higher mortality. Severely ill persons on mechanical ventilation should be especially monitored for development of ICAD.


Subject(s)
Hospital Mortality , Humans , Male , Qatar/epidemiology , Female , Middle Aged , Risk Factors , Aged , Candidiasis/epidemiology , Candidiasis/microbiology , Candidiasis/mortality , Candidiasis/drug therapy , Adult , Candida auris , Candidiasis, Invasive/epidemiology , Candidiasis, Invasive/mortality , Candidiasis, Invasive/microbiology , Candidiasis, Invasive/drug therapy , Antifungal Agents/therapeutic use , Length of Stay , Retrospective Studies , Candida/isolation & purification , Candida/pathogenicity
4.
Nanotechnology ; 35(33)2024 May 30.
Article in English | MEDLINE | ID: mdl-38749415

ABSTRACT

Candida auris, a rapidly emerging multidrug-resistant fungal pathogen, poses a global health threat, with cases reported in over 47 countries. Conventional detection methods struggle, and the increasing resistance ofC. auristo antifungal agents has limited treatment options. Nanoparticle-based therapies, utilizing materials like silver, carbon, zinc oxide, titanium dioxide, polymer, and gold, show promise in effectively treating cutaneous candidiasis. This review explores recent advancements in nanoparticle-based therapies, emphasizing their potential to revolutionize antifungal therapy, particularly in combatingC. aurisinfections. The discussion delves into mechanisms of action, combinations of nanomaterials, and their application against multidrug-resistant fungal pathogens, offering exciting prospects for improved clinical outcomes and reduced mortality rates. The aim is to inspire further research, ushering in a new era in the fight against multidrug-resistant fungal infections, paving the way for more effective and targeted therapeutic interventions.


Subject(s)
Antifungal Agents , Candidiasis , Drug Resistance, Multiple, Fungal , Nanoparticles , Humans , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Candidiasis/drug therapy , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Candida auris/drug effects , Animals , Metal Nanoparticles/chemistry , Metal Nanoparticles/therapeutic use
5.
J Med Microbiol ; 73(5)2024 May.
Article in English | MEDLINE | ID: mdl-38743468

ABSTRACT

Introduction. Innovative antifungal therapies are of crucial importance to combat the potentially life-threatening infections linked to the multidrug-resistant fungal pathogen Candida auris. Induction of regulated cell death, apoptosis, could provide an outline for future therapeutics. Human antimicrobial peptides (AMPs), well-known antifungal compounds, have shown the ability to induce apoptosis in pathogenic fungi.Hypothesis/Gap Statement . Although it is known that AMPs possess antifungal activity against C. auris, their ability to induce apoptosis requires further investigations.Aim. This study evaluated the effects of AMPs on the induction of apoptosis in C. auris.Methods. Human neutrophil peptide-1 (HNP-1), human ß-Defensins-3 (hBD-3) and human salivary histatin 5 (His 5) were assessed against two clinical C. auris isolates. Apoptosis hallmarks were examined using FITC-Annexin V/PI double labelling assay and terminal deoxynucleotidyl transferase deoxynucleotidyl transferase nick-end labelling (TUNEL) to detect phosphatidylserine externalization and DNA fragmentation, respectively. Then, several intracellular triggers were studied using JC-10 staining, spectrophotometric assay and 2',7'-dichlorofluorescin diacetate staining to measure the mitochondrial membrane potential, cytochrome-c release and reactive oxygen species (ROS) production, respectively.Results and conclusion. FITC-Annexin V/PI staining and TUNEL analysis revealed that exposure of C. auris cells to HNP-1 and hBD-3 triggered both early and late apoptosis, while His 5 caused significant necrosis. Furthermore, HNP-1 and hBD-3 induced significant mitochondrial membrane depolarization, which resulted in substantial cytochrome c release. In contrast to His 5, which showed minimal mitochondrial depolarization and no cytochrome c release. At last, all peptides significantly increased ROS production, which is related to both types of cell death. Therefore, these peptides represent promising and effective antifungal agents for treating invasive infections caused by multidrug-resistant C. auris.


Subject(s)
Antifungal Agents , Apoptosis , Candida auris , Histatins , Reactive Oxygen Species , Apoptosis/drug effects , Humans , Antifungal Agents/pharmacology , Histatins/pharmacology , Reactive Oxygen Species/metabolism , Candida auris/drug effects , beta-Defensins/pharmacology , Membrane Potential, Mitochondrial/drug effects , alpha-Defensins/pharmacology , Microbial Sensitivity Tests , Antimicrobial Peptides/pharmacology , Antimicrobial Peptides/chemistry , Cytochromes c/metabolism , DNA Fragmentation/drug effects , Candidiasis/drug therapy , Candidiasis/microbiology
6.
Arch Microbiol ; 206(6): 253, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38727738

ABSTRACT

Candida auris is an invasive fungal pathogen of high concern due to acquired drug tolerance against antifungals used in clinics. The prolonged persistence on biotic and abiotic surfaces can result in onset of hospital outbreaks causing serious health threat. An in depth understanding of pathology of C. auris is highly desirable for development of efficient therapeutics. Non-coding RNAs play crucial role in fungal pathology. However, the information about ncRNAs is scanty to be utilized. Herein our aim is to identify long noncoding RNAs with potent role in pathobiology of C. auris. Thereby, we analyzed the transcriptomics data of C. auris infection in blood for identification of potential lncRNAs with regulatory role in determining invasion, survival or drug tolerance under infection conditions. Interestingly, we found 275 lncRNAs, out of which 253 matched with lncRNAs reported in Candidamine, corroborating for our accurate data analysis pipeline. Nevertheless, we obtained 23 novel lncRNAs not reported earlier. Three lncRNAs were found to be under expressed throughout the course of infection, in the transcriptomics data. 16 of potent lncRNAs were found to be coexpressed with coding genes, emphasizing for their functional role. Noteworthy, these ncRNAs are expressed from intergenic regions of the genes associated with transporters, metabolism, cell wall biogenesis. This study recommends for possible association between lncRNA expression and C. auris pathogenesis.


Subject(s)
Candida auris , Candidiasis , Host Microbial Interactions , RNA, Long Noncoding , RNA, Long Noncoding/genetics , RNA, Long Noncoding/isolation & purification , Gene Expression Profiling , Computer Simulation , Genome-Wide Association Study , Candida auris/genetics , Candida auris/pathogenicity , Candidiasis/blood , Candidiasis/microbiology , Sepsis/microbiology , Host Microbial Interactions/genetics , Humans
7.
Mycopathologia ; 189(3): 35, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637433

ABSTRACT

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.


Subject(s)
Antifungal Agents , Candidiasis , Humans , Antifungal Agents/pharmacology , Candidiasis/microbiology , Candida auris , Candida , Amphotericin B/pharmacology , Drug Resistance, Fungal/genetics , Microbial Sensitivity Tests
8.
Emerg Infect Dis ; 30(13): S36-S40, 2024 04.
Article in English | MEDLINE | ID: mdl-38561642

ABSTRACT

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.


Subject(s)
Candida , Candidiasis , Humans , Candidiasis/microbiology , Candida auris , Antifungal Agents/therapeutic use , Correctional Facilities
9.
J Ethnopharmacol ; 330: 118240, 2024 Aug 10.
Article in English | MEDLINE | ID: mdl-38677574

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Candida auris poses a severe global health threat, with many strains resistant to antifungal treatments, complicating therapy. Exploring natural compounds alongside conventional drugs offers promising therapeutic avenues. The antifungal potential of the ethanolic extract from Caryocar brasiliense (Cb-EE), a plant native to the Brazilian cerrado and renowned for its medicinal properties, was investigated against C. auris. AIM OF THE STUDY: The study examined the chemical composition, antifungal activity, mechanisms of action, and in vivo effects of Cb-EE. MATERIALS AND METHODS: Leaves of C. brasiliense were processed to extract ethanolic extract, which was evaluated for phenolic compounds, flavonoids, and tannins. The antifungal capacity was determined through broth microdilution and checkerboard methods, assessing interaction with conventional antifungals. RESULTS: Cb-EE demonstrated fungistatic activity against various Candida species and Cryptococcus neoformans. Synergy with fluconazole and additive effects with other drugs were observed. Cb-EE inhibited C. auris growth, with the combination of fluconazole extending inhibition. Mechanistic studies revealed interference with fungal membranes, confirmed by sorbitol protection assays, cellular permeability tests, and scanning electron microscopy (SEM). Hemocompatibility and in vivo toxicity tests on Tenebrio molitor showed safety. CONCLUSION: Cb-EE, alone or in combination with fluconazole, effectively treated C. auris infections in vitro and in vivo, suggesting its prospective role as an antifungal agent against this emerging pathogen.


Subject(s)
Antifungal Agents , Drug Resistance, Multiple, Fungal , Microbial Sensitivity Tests , Plant Extracts , Plant Leaves , Antifungal Agents/pharmacology , Antifungal Agents/isolation & purification , Animals , Plant Extracts/pharmacology , Plant Leaves/chemistry , Candida auris/drug effects , Candida auris/isolation & purification , Fluconazole/pharmacology , Tenebrio , Drug Synergism , Brazil , Candida/drug effects , Cryptococcus neoformans/drug effects
10.
Microb Genom ; 10(4)2024 Apr.
Article in English | MEDLINE | ID: mdl-38630608

ABSTRACT

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.


Subject(s)
Candida auris , Candidiasis , Humans , Phylogeny , Candidiasis/microbiology , Candida/genetics , Biological Evolution
11.
J Mycol Med ; 34(2): 101477, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38574412

ABSTRACT

BACKGROUND: Candida auris was sporadically detected in Greece until 2019. Thereupon, there has been an increase in isolations among inpatients of healthcare facilities. AIM: We aim to report active surveillance data on MALDI-TOF confirmed Candida auris cases and outbreaks, from November 2019 to September 2021. METHODS: A retrospective study on hospital-based Candida auris data, over a 23-month period was conducted, involving 11 hospitals within Attica region. Antifungal susceptibility testing and genotyping were conducted. Case mortality and fatality rates were calculated and p-values less than 0.05 were considered statistically significant. Infection control measures were enforced and enhanced. RESULTS: Twenty cases with invasive infection and 25 colonized were identified (median age: 72 years), all admitted to hospitals for reasons other than fungal infections. Median hospitalisation time until diagnosis was 26 days. Common risk factors among cases were the presence of indwelling devices (91.1 %), concurrent bacterial infections during hospitalisation (60.0 %), multiple antimicrobial drug treatment courses prior to hospitalisation (57.8 %), and admission in the ICU (44.4 %). Overall mortality rate was 53 %, after a median of 41.5 hospitalisation days. Resistance to fluconazole and amphotericin B was identified in 100 % and 3 % of tested clinical isolates, respectively. All isolates belonged to South Asian clade I. Outbreaks were identified in six hospitals, while remaining hospitals detected sporadic C. auris cases. CONCLUSION: Candida auris has proven its ability to rapidly spread and persist among inpatients and environment of healthcare facilities. Surveillance focused on the presence of risk factors and local epidemiology, and implementation of strict infection control measures remain the most useful interventions.


Subject(s)
Antifungal Agents , Candida auris , Candidiasis , Cross Infection , Disease Outbreaks , Microbial Sensitivity Tests , Humans , Greece/epidemiology , Aged , Disease Outbreaks/statistics & numerical data , Male , Female , Retrospective Studies , Middle Aged , Aged, 80 and over , Antifungal Agents/therapeutic use , Antifungal Agents/pharmacology , Candidiasis/epidemiology , Candidiasis/microbiology , Cross Infection/epidemiology , Cross Infection/microbiology , Candida auris/genetics , Adult , Hospitals/statistics & numerical data , Health Facilities/statistics & numerical data , Infection Control , Risk Factors , Drug Resistance, Fungal , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Candida/isolation & purification , Candida/drug effects , Candida/classification , Hospitalization/statistics & numerical data
12.
Front Cell Infect Microbiol ; 14: 1389020, 2024.
Article in English | MEDLINE | ID: mdl-38601736

ABSTRACT

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.


Subject(s)
Antifungal Agents , Candidiasis, Invasive , Candidiasis , Humans , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Candida albicans , Fluconazole/pharmacology , Fluconazole/therapeutic use , Candida auris , Peptides/pharmacology , Microbial Sensitivity Tests , Drug Resistance, Fungal
13.
Mycoses ; 67(4): e13723, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38551121

ABSTRACT

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.


Subject(s)
Amphotericin B , Antifungal Agents , Fatty Acids, Monounsaturated , Humans , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Amphotericin B/pharmacology , Fluconazole/pharmacology , Candida auris , Candida , Saccharomyces cerevisiae , Microbial Sensitivity Tests , Sphingolipids/pharmacology
14.
FEMS Yeast Res ; 242024 Jan 09.
Article in English | MEDLINE | ID: mdl-38444195

ABSTRACT

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.


Subject(s)
Antifungal Agents , Candida , Antifungal Agents/pharmacology , Candida auris , Sphingolipids , Drug Resistance, Fungal , Microbial Sensitivity Tests
15.
mBio ; 15(4): e0014624, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38477572

ABSTRACT

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.


Subject(s)
Candida , Candidiasis , Dogs , Humans , Animals , Candida/genetics , Candida/isolation & purification , Candidiasis/veterinary , Candidiasis/microbiology , Candida auris , Kansas , Climate Change , Fungi , Zoonoses , Mouth
16.
Photochem Photobiol Sci ; 23(4): 681-692, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38446403

ABSTRACT

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.


Subject(s)
Candida auris , Saccharomyces cerevisiae , Humans , Photosensitizing Agents/pharmacology , Light , Ultraviolet Rays , Antifungal Agents , Microbial Sensitivity Tests
17.
PLoS Pathog ; 20(3): e1012076, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38466738

ABSTRACT

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.


Subject(s)
Antifungal Agents , Candida , Humans , Antifungal Agents/therapeutic use , Candida/genetics , Candida auris , Virulence , Drug Resistance, Fungal , Adhesins, Bacterial/metabolism , Microbial Sensitivity Tests
18.
Microbiol Spectr ; 12(4): e0227823, 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38440972

ABSTRACT

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.


Subject(s)
Candida auris , Farnesol , Phenylethyl Alcohol/analogs & derivatives , Farnesol/pharmacology , Farnesol/metabolism , Calcium/metabolism , Calcium/pharmacology , Magnesium/metabolism , Magnesium/pharmacology , Biofilms , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Antifungal Agents/metabolism , Ergosterol , Iron/metabolism , Fatty Acids/metabolism , Candida albicans , Microbial Sensitivity Tests
20.
Indian J Med Microbiol ; 48: 100555, 2024.
Article in English | MEDLINE | ID: mdl-38428528

ABSTRACT

Meningitis in patients with ventriculo-peritoneal shunt (VP shunt) caused by various species of Candida have been widely described in literature. However, reports describing Candida auris as a cause of meningitis is limited. In this case report we describe a case of multidrug resistant Candida auris meningitis secondary to VP shunt infection successfully treated with intrathecal amphotericin B deoxycholate and intravenous liposomal amphotericin B. This is the second case report of successful treatment of Candida auris meningitis from India. More literature regarding the use of intrathecal/intraventricular echinocandins including optimal dosing and duration of therapy is needed.


Subject(s)
Amphotericin B , Antifungal Agents , Candidiasis , Deoxycholic Acid , Meningitis, Fungal , Ventriculoperitoneal Shunt , Humans , Ventriculoperitoneal Shunt/adverse effects , Amphotericin B/therapeutic use , Amphotericin B/administration & dosage , Antifungal Agents/therapeutic use , Antifungal Agents/administration & dosage , Candidiasis/drug therapy , Candidiasis/microbiology , Deoxycholic Acid/therapeutic use , Meningitis, Fungal/drug therapy , Meningitis, Fungal/microbiology , Meningitis, Fungal/diagnosis , Candida auris , Male , India , Drug Combinations , Drug Resistance, Multiple, Fungal , Treatment Outcome , Adult , Female
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