scholarly journals Comparative molecular and immunoregulatory analysis of extracellular vesicles from Candida albicans and Candida auris

2020 ◽  
Author(s):  
Daniel Zamith-Miranda ◽  
Heino M. Heyman ◽  
Sneha P. Couvillion ◽  
Radames J. B. Cordero ◽  
Macio L. Rodrigues ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Pathogenic Fungus ◽  
Cell Monolayer ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Immune Defense ◽  
Potential Contribution ◽  
Candida Auris ◽  
Activation Markers ◽  
Healthcare Associated

AbstractCandida auris is a recently described multidrug-resistant pathogenic fungus that is increasingly responsible for healthcare associated outbreaks across the world. Bloodstream infections of this fungus cause death in up to 70% of the cases. Aggravating this scenario, C. auris’ disease-promoting mechanisms are poorly understood. Fungi release extracellular vesicles (EVs) carrying a broad range of molecules including proteins, lipids, carbohydrates, pigments, and RNA, many of which are virulence factors. Here, we carried out a comparative molecular characterization of C. auris and C. albicans EVs and evaluated their capacity to modulate effector mechanisms of host immune defense. Using proteomics, lipidomics, and transcriptomics, we found that C. auris released EVs with payloads that were strikingly different from EVs released by C. albicans. EVs released by C. auris potentiated the adhesion of this yeast to an epithelial cell monolayer. C. auris EVs also induced the expression of surface activation markers and cytokines by bone marrow-derived dendritic cells. Altogether, our findings show distinct profiles and properties of EVs released by C. auris and by C. albicans, and highlight the potential contribution of C. auris EVs to the pathogenesis of this emerging pathogen.

Bloodstream Infections With Candida auris Among Children in Colombia: Clinical Characteristics and Outcomes of 34 Cases

2020 ◽  
Author(s):  
Indira Berrio ◽  
Diego H Caceres ◽  
Wilfrido Coronell R ◽  
Soraya Salcedo ◽  
Laura Mora ◽  
...  
Keyword(s):  
Organ Transplant ◽  
Bloodstream Infections ◽  
Venous Catheter ◽  
Multidrug Resistant ◽  
Solid Organ ◽  
Central Venous ◽  
Candida Auris ◽  
Healthcare Settings ◽  
Invasive Infections ◽  
Healthcare Associated

Abstract Background Candida auris is an emerging multidrug-resistant yeast that can cause invasive infections and healthcare-associated outbreaks. Here, we describe 34 cases of pediatric C. auris bloodstream infections (BSIs) identified during July 2014–October 2017 in 2 hospitals in Colombia. Methods We conducted a retrospective review of microbiology records for possible C. auris cases in 2 hospitals in Barranquilla and Cartagena. BSIs that occurred in patients aged <18 years confirmed as C. auris were included in this analysis. Results We identified 34 children with C. auris BSIs. Twenty-two (65%) patients were male, 21% were aged <28 days, 47% were aged 29–365 days, and 32% were aged >1 year. Underlying conditions included preterm birth (26%), being malnourished (59%), cancer (12%), solid-organ transplant (3%), and renal disease (3%). Eighty-two percent had a central venous catheter (CVC), 82% were on respiratory support, 56% received total parenteral nutrition (TPN), 15% had a surgical procedure, and 9% received hemodialysis. Preinfection inpatient stay was 22 days (interquartile range, 19–33 days), and in-hospital mortality was 41%. Conclusions Candida auris affects children with a variety of medical conditions including prematurity and malignancy, as well as children with CVCs and those who receive TPN. Mortality was high, with nearly half of patients dying before discharge. However, unlike most other Candida species, C. auris can be transmitted in healthcare settings, as suggested by the close clustering of cases in time at each of the hospitals. Candida auris is an emerging multidrug-resistant yeast that can cause invasive infections and healthcare-associated outbreaks. This report describes 34 cases of pediatric C. auris bloodstream infections, identified in two hospitals in Colombia, South America.

scholarly journals Comparative Molecular and Immunoregulatory Analysis of Extracellular Vesicles from Candida albicans and Candida auris

mSystems ◽  
2021 ◽  
Vol 6 (4) ◽  
Author(s):  
Daniel Zamith-Miranda ◽  
Heino M. Heyman ◽  
Sneha P. Couvillion ◽  
Radames J. B. Cordero ◽  
Marcio L. Rodrigues ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Extracellular Vesicles ◽  
Virulence Factors ◽  
Nosocomial Infections ◽  
Pathogenic Fungus ◽  
Multidrug Resistant ◽  
Candida Auris ◽  
Content Type

Candida auris is a recently described multidrug-resistant pathogenic fungus that is responsible for outbreaks across the globe, particularly in the context of nosocomial infections. Its virulence factors and pathogenesis are poorly understood.

scholarly journals Facile Bio-Fabrication of Ag-Cu-Co Trimetallic Nanoparticles and Its Fungicidal Activity against Candida auris

2021 ◽  
Vol 7 (1) ◽  
pp. 62 ◽  
Author(s):  
Majid Rasool Kamli ◽  
Vartika Srivastava ◽  
Nahid H. Hajrah ◽  
Jamal S. M. Sabir ◽  
Khalid Rehman Hakeem ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Antimicrobial Properties ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Biologically Active ◽  
Phase Cell ◽  
Candida Auris ◽  
Medical Problems ◽  
One Pot ◽  
X Ray

Candida auris is an emergent multidrug-resistant pathogen that can lead to severe bloodstream infections associated with high mortality rates, especially in hospitalized individuals suffering from serious medical problems. As Candida auris is often multidrug-resistant, there is a persistent demand for new antimycotic drugs with novel antifungal action mechanisms. Here, we reported the facile, one-pot, one-step biosynthesis of biologically active Ag-Cu-Co trimetallic nanoparticles using the aqueous extract of Salvia officinalis rich in polyphenols and flavonoids. These medicinally important phytochemicals act as a reducing agent and stabilize/capping in the nanoparticles’ fabrication process. Fourier Transform-Infrared, Scanning electron microscopy, Transmission Electron Microscopy, Energy dispersive X-Ray, X-ray powder diffraction and Thermogravimetric analysis (TGA) measurements were used to classify the as-synthesized nanoparticles. Moreover, we evaluated the antifungal mechanism of as-synthesized nanoparticles against different clinical isolates of C. auris. The minimum inhibitory concentrations and minimum fungicidal concentrations ranged from 0.39–0.78 μg/mL and 0.78–1.56 μg/mL. Cell count and viability assay further validated the fungicidal potential of Ag-Cu-Co trimetallic nanoparticles. The comprehensive analysis showed that these trimetallic nanoparticles could induce apoptosis and G2/M phase cell cycle arrest in C. auris. Furthermore, Ag-Cu-Co trimetallic nanoparticles exhibit enhanced antimicrobial properties compared to their monometallic counterparts attributed to the synergistic effect of Ag, Cu and Co present in the as-synthesized nanoparticles. Therefore, the present study suggests that the Ag-Cu-Co trimetallic nanoparticles hold the capacity to be a lead for antifungal drug development against C. auris infections.

scholarly journals Two Candida auris Cases in Germany with No Recent Contact to Foreign Healthcare—Epidemiological and Microbiological Investigations

2021 ◽  
Vol 7 (5) ◽  
pp. 380
Author(s):  
Joerg Steinmann ◽  
Thomas Schrauzer ◽  
Lisa Kirchhoff ◽  
Jacques F. Meis ◽  
Peter-Michael Rath
Keyword(s):  
South Asian ◽  
Multidrug Resistant ◽  
Health Care Facilities ◽  
Candida Auris ◽  
Contact Precautions ◽  
Asian Clade ◽  
Care Facilities ◽  
Long Time ◽  
European Health ◽  
Healthcare Associated

Candida auris has become a global fungal public health threat. This multidrug-resistant yeast is associated with nosocomial intra- and interhospital transmissions causing healthcare-associated infections. Here, we report on two C. auris cases from Germany. The two patients stayed in Germany for a long time before C. auris was detected during their hospitalization. The patients were isolated in single rooms with contact precautions. No nosocomial transmissions were detected within the hospital. Both C. auris isolates exhibited high minimum inhibitory concentrations (MICs) of fluconazole and one isolate additionally high MICs against the echinocandins. Microsatellite genotyping showed that both strains belong to the South Asian clade. These two cases are examples for appropriate in-hospital care and infection control without further nosocomial spread. Awareness for this emerging, multidrug-resistant pathogen is justified and systematic surveillance in European health care facilities should be performed.

scholarly journals Multi-omics Signature of Candida auris, an Emerging and Multidrug-Resistant Pathogen

mSystems ◽  
2019 ◽  
Vol 4 (4) ◽  
Author(s):  
Daniel Zamith-Miranda ◽  
Heino M. Heyman ◽  
Levi G. Cleare ◽  
Sneha P. Couvillion ◽  
Geremy C. Clair ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Protein Content ◽  
Pathogenic Fungus ◽  
Multidrug Resistant ◽  
Antifungal Resistance ◽  
Clinical Isolates ◽  
Medical Mycology ◽  
Carbon Utilization ◽  
Candida Auris ◽  
Content Type

ABSTRACT Candida auris is a recently described pathogenic fungus that is causing invasive outbreaks on all continents. The fungus is of high concern given the numbers of multidrug-resistant strains that have been isolated in distinct sites across the globe. The fact that its diagnosis is still problematic suggests that the spreading of the pathogen remains underestimated. Notably, the molecular mechanisms of virulence and antifungal resistance employed by this new species are largely unknown. In the present work, we compared two clinical isolates of C. auris with distinct drug susceptibility profiles and a Candida albicans reference strain using a multi-omics approach. Our results show that, despite the distinct drug resistance profile, both C. auris isolates appear to be very similar, albeit with a few notable differences. However, compared to C. albicans both C. auris isolates have major differences regarding their carbon utilization and downstream lipid and protein content, suggesting a multifactorial mechanism of drug resistance. The molecular profile displayed by C. auris helps to explain the antifungal resistance and virulence phenotypes of this new emerging pathogen. IMPORTANCE Candida auris was first described in Japan in 2009 and has now been the cause of significant outbreaks across the globe. The high number of isolates that are resistant to one or more antifungals, as well as the high mortality rates from patients with bloodstream infections, has attracted the attention of the medical mycology, infectious disease, and public health communities to this pathogenic fungus. In the current work, we performed a broad multi-omics approach on two clinical isolates isolated in New York, the most affected area in the United States and found that the omic profile of C. auris differs significantly from C. albicans. In addition to our insights into C. auris carbon utilization and lipid and protein content, we believe that the availability of these data will enhance our ability to combat this rapidly emerging pathogenic yeast.

scholarly journals 1687. High-Rates of Candida auris Carriage and Co-Colonization with Multidrug-Resistant Organisms (MDROs)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S617-S617
Author(s):  
Ruby Barza ◽  
Parul Patel ◽  
Jignesh Patel ◽  
Lauren E Droske ◽  
Donna Schora ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
High Rate ◽  
Diffusion Method ◽  
Candida Auris ◽  
Prevalence Survey ◽  
E Coli ◽  
Carbapenem Resistant ◽  
Few Data ◽  
Healthcare Associated

Abstract Background Candida auris is an emerging multidrug-resistant pathogen that can persist in the environment and lead to healthcare-associated outbreaks. Residents of long-term acute care hospitals (LTACHs) are at particular risk for carriage of both MDROs and C. auris. However, there are few data on co-colonization rates of C. auris with other MDROs in LTACHs. Methods We conducted a point prevalence survey for MDROs, C. auris and C. difficile in a Chicago LTACH in March 2019. A combined axilla/groin E-swab (Copan) was collected and plated for C. auris isolation using CHROMagar Candida (Hardy). A rectal E-swab (Copan) was collected for C difficile PCR and MDRO detection including Carbapenem-resistant Enterobacteriaceae (CRE), Extended-spectrum B-lactamases (ESBLs) and Vancomycin-resistant Enterococci (VRE). Each swab was plated directly on VACC agar (Vancomycin, Amphotericin B, Ceftazidime, Clindamycin) and CHROMagar ESBL (Hardy). Bruker MALDI-TOF was used for bacterial and yeast identification and disc diffusion method for antimicrobial susceptibility testing. ESBL phenotypic confirmation was done using double-disc synergy method per CLSI guidelines. Carbapenemase production was confirmed using Xpert Carba-R assay (Cepheid). C. difficile PCR was performed using Xpert C. difficile/Epi assay (Cepheid). Results Of 38 patients 36 were eligible for the study (2 patients declined). Overall, 26/36 (72%) patients had an MDRO. Eight (22%) patients were positive for C. auris. Eight (22%) patients had ESBLs (2 P. mirabilis and 6 E. coli), six (17%) had CREs that were all blaKPC positive (4 K. pneumonia, 1 E. coli, and K. pneumoniae). Eight (22%) patients were positive for other gram-negative (GN)-MDROs including 1 A. baumanii, 3 P. aeruginosa, 2 E. cloacae, 1 E. asburiae and 1 P. aeruginosa, and A. baumanii. 20 patients (56%) had VRE colonization. Five (14%) were C. difficile PCR positive. 7/ 8 (87.5%) patients with C. auris were also colonized with another MDRO (2 VRE, 1 ESBL, 1 VRE, ESBL and KPC, 1 VRE and GN-MDRO, 1 VRE, ESBL and GN-MDRO, 1 VRE, KPC, and GN-MDRO). Conclusion We found a high rate of MDRO co-colonization among patients with C. auris carriage. Continuous active surveillance may be appropriate in LTACHs to limit the spread of C. auris and other MDROs. Disclosures All authors: No reported disclosures.

scholarly journals A Review of the Innate Immune Evasion Mechanisms and Status of Vaccine Development of Klebsiella pneumonia

2021 ◽  
pp. 33-47
Author(s):  
Fredrick Ruo Tiria ◽  
Lillian Musila
Keyword(s):  
Immune Evasion ◽  
Antimicrobial Agents ◽  
Vaccine Development ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Immune Defense ◽  
Klebsiella Pneumonia ◽  
High Morbidity ◽  
Pharmaceutical Industries ◽  
Tract Infections

Klebsiella pneumoniae (KP) is a human pathogen causing a broad spectrum of diseases such as urinary tract infections (UTI), pneumonia, pyogenic liver abscess, bloodstream infections, and sepsis. Neonate, geriatric and immunocompromised individuals are the most vulnerable to KP infections. The success of KP as an infectious agent is due to the evolution of various mechanisms to evade the host's immune system. These diverse mechanisms have led to the dominance of KP infections in community settings where hypervirulent strains predominate and in hospital-acquired infections where multidrug-resistant strains predominate. KP infections in the past decades have been increasingly associated with high morbidity and mortality due to the emergence of multidrug-resistant and hypervirulent strains capable of evading both the internal immune defense mechanisms and external antimicrobial agents. The pharmaceutical industries have very few and often expensive new antibiotics in the pipeline, offering little hope for antibiotic therapy. The development of new therapeutic strategies such as polyvalent, biconjugate vaccines that can provide protective immunity, especially against vulnerable populations, can mitigate the effects of KP infections. In this review, we discuss the virulence mechanisms of KP and how it evades the innate host immunity, and the interplay between the virulence and immune evasion strategies. The progress in the search for a vaccine to protect against KP infections will also be highlighted.

scholarly journals What Do We Know about Candida auris? State of the Art, Knowledge Gaps, and Future Directions

2021 ◽  
Vol 9 (10) ◽  
pp. 2177
Author(s):  
Victor Garcia-Bustos ◽  
Marta D. Cabanero-Navalon ◽  
Amparo Ruiz-Saurí ◽  
Alba C. Ruiz-Gaitán ◽  
Miguel Salavert ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Current Evidence ◽  
Knowledge Gaps ◽  
Candida Auris ◽  
Future Directions ◽  
International Agencies ◽  
Health Authorities ◽  
Control And Prevention ◽  
Global Threat ◽  
Healthcare Associated

Candida auris has unprecedently emerged as a multidrug resistant fungal pathogen, considered a serious global threat due to its potential to cause nosocomial outbreaks and deep-seated infections with staggering transmissibility and mortality, that has put health authorities and institutions worldwide in check for more than a decade now. Due to its unique features not observed in other yeasts, it has been categorised as an urgent threat by the Centers for Disease Control and Prevention and other international agencies. Moreover, epidemiological alerts have been released in view of the increase of healthcare-associated C. auris outbreaks in the context of the COVID-19 pandemic. This review summarises the current evidence on C. auris since its first description, from virulence to treatment and outbreak control, and highlights the knowledge gaps and future directions for research efforts.

scholarly journals 266. Clinical Profile and Treatment Outcomes of Candida auris Isolates from a Tertiary Care Hospital in South India

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S147-S148
Author(s):  
Anup R Warrier ◽  
Arun Wilson ◽  
Rachana Babu ◽  
Shilpa Prakash ◽  
Madhav Bhargava
Keyword(s):  
Treatment Outcomes ◽  
Tertiary Care ◽  
Case Series ◽  
Bloodstream Infections ◽  
Multidrug Resistant ◽  
Wound Management ◽  
Care Hospital ◽  
Candida Auris ◽  
Sensitivity Pattern ◽  
Anti Fungal

Abstract Background Candida auris is an emerging multidrug-resistant fungus that is rapidly spreading worldwide. In publications from India, it has already accounted for >5% of candidemia in a national survey of ICUs and as much as 30% of candidemia at individual hospitals,but data on treatment outcomes is scarce. This study reviews the various clinical syndromes in our case series, the treatment regimens we opted and their clinical outcomes. Methods The present study was a retrospective observational analysis of candida auris isolates obtained from patients admitted in a Aster Medcity, Kochi. Duration of study was 4 months (September 2018 to December 2018). Laboratory confirmation of the candida auris isolates was done as per CDC recommendations for Vitek2. Vitek2 was also used for obtaining the antifungal sensitivity pattern for these isolates. Results We had 18 cases of Candida auris identified. The most common syndrome was surgical site infections, 9 out of 18 (50%), followed by Catheter-Associated Urinary Tract Infection (CAUTI 5/18; 28%). We had 3 patients with Central Line-Associated Blood Stream Infections (CLABSI) and one patient who had secondary peritonitis. The overall mortality was 28% (5/18)—mostly contributed by the CLABSI. Considering breakpoints from CLSI as well as CDC, all isolates had their minimum inhibitory concentration (MIC) in the sensitive range for Caspofungin. Both Amphotericin b and Voriconazole had MICs in susceptible range for less than 50% of the isolates and almost all isolates were having very high MICs for Fluconazole, highlighting the increased levels of antifungal resistance which has made this Candida species notorious. Conclusion Candida auris is an emerging nosocomial pathogen in India with serious outbreak potential. The anti-fungal susceptibility is indicative of a multidrug-resistant pattern—with favorable MIC to Echinocandin and Voriconazole. Complicated bloodstream infections had high mortality inspite of early Echinocandin use. Of note, 6 patients out of 18, were managed successfully without any anti-fungal use; as they had either mild UTI (fever spikes resolved with catheter removal) or superfical SSI which could be treated with topical wound management. Disclosures All authors: No reported disclosures.

Prevalence, epidemiology and clinical outcome of Candida auris infections: Experience from a tertiary care hospital in Jaipur

2021 ◽  
pp. 004947552110286
Author(s):  
Daisy Bacchani ◽  
Ekadashi Rajni ◽  
Vishnu K Garg ◽  
Richa Sharma ◽  
Ved P Mamoria
Keyword(s):  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Multidrug Resistant ◽  
Care Hospital ◽  
Emerging Pathogen ◽  
Broad Spectrum Antibiotic ◽  
Candida Auris ◽  
History Of ◽  
Echinocandin Resistance ◽  
Healthcare Associated

Candida auris is identified as an emerging pathogen worldwide. It is multidrug resistant and causes invasive healthcare-associated infections. Our retrospective study was conducted to determine the prevalence and epidemiology of C. auris infections in a tertiary care hospital in Jaipur. 24 clinical C. auris strains were included, most being from urine. The majority patients needed intensive care and had at least one underlying co-morbid condition. A history of broad-spectrum antibiotic or antifungal usage was present in 85%. Fluconazole, voriconazole, amphotericin B and 5-fluorocytosine resistance was seen in 96, 42, 33 and 8% isolates respectively. No echinocandin resistance was noted.

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