Multidrug-Resistant Candida haemulonii and C. auris, Tel Aviv, Israel.
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ABSTRACT:
SUBMITTER: Ben-Ami R
PROVIDER: S-EPMC5324804 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Candida haemulonii is an emerging multidrug-resistant yeast that can cause invasive candidiasis. Here, we report the first genome sequence of C. haemulonii (isolate B11899) generated using PacBio sequencing technology. The estimated genome size was 13.3 Mb, with a GC content of 45.19%.
| S-EPMC5897814 | biostudies-literature
Project description:Candida auris is an emerging multidrug-resistant fungus that is rapidly spreading worldwide. Currently, C. auris cases have been reported globally from >30 countries. Most reported infections involve critically ill patients in hospitals, mainly in intensive care unit settings. Infection with C. auris is associated with high mortality rates, and it is often resistant to multiple classes of antifungal drugs. Despite the rapid global spread, it is difficult to predict the actual burden of the infection as the standard laboratory methods fail to correctly identify the fungi. Longer stays in healthcare facilities, use of tracheostomies and percutaneous endoscopic gastrostomy tubes, ventilators in clinical care units and mobile equipment in healthcare settings are shown as major risk factors of C. auris infection. Due to its propensity to cause outbreaks and its antifungal resistance, C. auris poses a risk for patients in healthcare facilities. The emergence of ?pan-resistant C. auris strains in some areas is an alarming signal for the disease with limited treatment options, high mortality rates, and the ability of the pathogen to spread easily in healthcare settings. In this regard, susceptibility testing on clinical isolates, mainly for patients treated with echinocandins, is needed. Increasing awareness about C. auris infection and advancing the diagnostic methods ?are also essential for early detection and control of the deadly fungal infection.
| S-EPMC7211321 | biostudies-literature
Project description:Subtype-A HIV was introduced into Israel in the mid-1990s, predominantly by immigrants from the former Soviet Union (FSU) infected via intravenous drug use (IVDU). HIV subsequently spread beyond the FSU-IVDU community. In 2012, a mini-HIV outbreak, associated with injection of amphetamine cathinone derivatives, started in Tel Aviv, prompting public health response. To assess current trends and the impact of the outbreak and control measures, we conducted a phyloepidemiologic analysis. Demographic and clinical records and HIV sequences were compiled from 312 subtype-A HIV-infected individuals attending the Tel-Aviv Sourasky Medical Center between 2005-2016, where >40% of all subtype-A HIV-infected individuals in Israel are undergoing care. Molecular evolutionary genetics analysis (MEGA) and ayesian evolutionary analysis sampling trees (BEAST) programs were implemented in a phylogenetic analysis of pol sequences. Reconstructed phylogenies were assessed in the context of demographic information and drug-resistance profiles. Clusters were identified as sequence populations with posterior probability ≥0.95 of having a recent common ancestor. After 2010, the subtype-A epidemic acquired substantial phylogenetic structure, having been unrecognized in studies covering the earlier period. Nearly 50% of all sequences were present in 11 distinct clusters consisting of 4-43 individuals. Cluster composition reflected transmission across ethnic groups, with men who have sex with men (MSM) playing an increasing role. The cathinone-associated cluster was larger than previously documented, containing variants that continued to spread within and beyond the IVDU community. Phyloepidemiologic analysis revealed diverse clusters of HIV infection with MSM having a central role in transmission across ethic groups. A mini outbreak was reduced by public health measures, but molecular evidence of ongoing transmission suggests additional measures are necessary.
| S-EPMC6657966 | biostudies-literature
Project description:The emergence of a multidrug-resistant Candida species, C. auris and C. haemulonii, has been reported worldwide. In Thailand, information on them is limited. We collected clinical isolates from Thai patients with invasive candidiasis. Both species were compared with a laboratory C. albicans strain. In vitro antifungal susceptibility and thermotolerance, and pathogenesis in the zebrafish model of infection were investigated. Both species demonstrated high minimal inhibitory concentrations to fluconazole and amphotericin B. Only C. auris tolerated high temperatures, like C. albicans. In a zebrafish swim-bladder-inoculation model, the C. auris-infected group had the highest mortality rate and infectivity, suggesting the highest virulence. The case fatality rates of C. auris, C. haemulonii, and C. albicans were 100%, 83.33%, and 51.52%, respectively. Further immunological studies revealed that both emerging Candida species stimulated genes involved in the proinflammatory cytokine group. Interestingly, the genes relating to leukocyte recruitment were downregulated only for C. auris infections. Almost all immune response genes to C. auris had a peak response at an early infection time, which contrasted with C. haemulonii. In conclusion, both emerging species were virulent in a zebrafish model of infection and could activate the inflammatory pathway. This study serves as a stepping stone for further pathogenesis studies of these important emerging species.
| S-EPMC8469599 | biostudies-literature
Project description:Candida auris is an emerging multidrug-resistant fungal pathogen causing nosocomial and invasive infections associated with high mortality. C. auris is commonly misidentified as several different yeast species by commercially available phenotypic identification platforms. Thus, there is an urgent need for a reliable diagnostic method. In this paper, we present fast, robust, easy-to-perform and interpret PCR and real-time PCR assays to identify C. auris and related species: Candida duobushaemulonii, Candida haemulonii, and Candida lusitaniae Targeting rDNA region nucleotide sequences, primers specific for C. auris only or C. auris and related species were designed. A panel of 140 clinical fungal isolates was used in both PCR and real-time PCR assays followed by electrophoresis or melting temperature analysis, respectively. The identification results from the assays were 100% concordant with DNA sequencing results. These molecular assays overcome the deficiencies of existing phenotypic tests to identify C. auris and related species.
| S-EPMC5527423 | biostudies-other
Project description:BackgroundCandida auris is a multidrug resistant, emerging agent of fungemia in humans. Its actual global distribution remains obscure as the current commercial methods of clinical diagnosis misidentify it as C. haemulonii. Here we report the first draft genome of C. auris to explore the genomic basis of virulence and unique differences that could be employed for differential diagnosis.ResultsMore than 99.5 % of the C. auris genomic reads did not align to the current whole (or draft) genome sequences of Candida albicans, Candida lusitaniae, Candida glabrata and Saccharomyces cerevisiae; thereby indicating its divergence from the active Candida clade. The genome spans around 12.49 Mb with 8527 predicted genes. Functional annotation revealed that among the sequenced Candida species, it is closest to the hemiascomycete species Clavispora lusitaniae. Comparison with the well-studied species Candida albicans showed that it shares significant virulence attributes with other pathogenic Candida species such as oligopeptide transporters, mannosyl transfersases, secreted proteases and genes involved in biofilm formation. We also identified a plethora of transporters belonging to the ABC and major facilitator superfamily along with known MDR transcription factors which explained its high tolerance to antifungal drugs.ConclusionsOur study emphasizes an urgent need for accurate fungal screening methods such as PCR and electrophoretic karyotyping to ensure proper management of fungemia. Our work highlights the potential genetic mechanisms involved in virulence and pathogenicity of an important emerging human pathogen namely C. auris. Owing to its diversity at the genomic scale; we expect the genome sequence to be a useful resource to map species specific differences that will help develop accurate diagnostic markers and better drug targets.
| S-EPMC4562351 | biostudies-literature
Project description:The purpose of this pilot cross-national study was to uncover similarities and differences in three areas that might affect the development of community-based programs targeting child maltreatment: behaviors considered to be maltreatment, perceived contributors to maltreatment, and whether the government or neighbors can do anything about maltreatment. Data were obtained from two neighborhood-based, cross-sectional surveys of adult caregivers of minors: one in Cleveland, USA, the other in Tel Aviv, Israel. The sample consisted of a total of 120 caregivers, in each city 20 residing in a low-SES neighborhood, 20 in a medium-SES neighborhood, and 20 in an elevated-SES neighborhood. Participants were asked (a) to provide three examples of behaviors they considered to be child abuse, (b) to rate the degree to which each of 13 factors contribute to child maltreatment, and (c) to rate the degree to which they agreed with a range of attitudes about maltreatment. The same coding scheme was used in both sites. Logistic regression analyses assessed city differences in dichotomous outcomes, while linear regression analyses assessed city differences in ratings of continuous outcomes. Analyses adjusted for individual and neighborhood characteristics, and accounted for residential clustering in neighborhoods. Primary results indicated that residence in Tel Aviv was associated with greater odds of citing emotional/psychological abuse compared to Cleveland residents. Also compared to Cleveland residents, Tel Aviv residents (a) viewed family structure, family values, religion, child-raising knowledge, and personal history of maltreatment as contributing less to maltreatment, (b) were less likely to agree that anyone could abuse a child or that spanking is necessary, and (c) had substantially greater odds of endorsing the government's ability to address child maltreatment. Concerning study implications, this investigation demonstrated the importance of context in shaping constructions of child maltreatment and the need for caution in replicating interventions without due consideration of potential differences in context, policy, and public opinion.
| S-EPMC6613203 | biostudies-literature
Project description:Candida auris is an emerging, multi-drug resistant, health care-associated fungal pathogen. Its predominant prevalence in hospitals and nursing homes indicates its ability to adhere to and colonize the skin, or persist in an environment outside the host-a trait unique from other Candida species. Besides being associated globally with life-threatening disseminated infections, C. auris also poses significant clinical challenges due to its ability to adhere to polymeric surfaces and form highly drug-resistant biofilms. Here, we performed bioinformatic studies to identify the presence of adhesin proteins in C. auris, with sequence as well as 3-D structural homologies to the major adhesin/invasin of C. albicans, Als3. Anti-Als3p antibodies generated by vaccinating mice with NDV-3A (a vaccine based on the N-terminus of Als3 protein formulated with alum) recognized C. auris in vitro, blocked its ability to form biofilms and enhanced macrophage-mediated killing of the fungus. Furthermore, NDV-3A vaccination induced significant levels of C. auris cross-reactive humoral and cellular immune responses, and protected immunosuppressed mice from lethal C. auris disseminated infection, compared to the control alum-vaccinated mice. The mechanism of protection is attributed to anti-Als3p antibodies and CD4+ T helper cells activating tissue macrophages. Finally, NDV-3A potentiated the protective efficacy of the antifungal drug micafungin, against C. auris candidemia. Identification of Als3-like adhesins in C. auris makes it a target for immunotherapeutic strategies using NDV-3A, a vaccine with known efficacy against other Candida species and safety as well as efficacy in clinical trials. Considering that C. auris can be resistant to almost all classes of antifungal drugs, such an approach has profound clinical relevance.
| S-EPMC6695204 | biostudies-literature
Project description: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.IMPORTANCECandida 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.
| S-EPMC6561322 | biostudies-literature
Project description:The limited therapeutic options and the recent emergence of multidrug-resistant Candida species present a significant challenge to human medicine and underscore the need for novel therapeutic approaches. Drug repurposing appears as a promising tool to augment the activity of current azole antifungals, especially against multidrug-resistant Candida auris In this study, we evaluated the fluconazole chemosensitization activities of 1,547 FDA-approved drugs and clinical molecules against azole-resistant C. auris This led to the discovery that lopinavir, an HIV protease inhibitor, is a potent agent capable of sensitizing C. auris to the effect of azole antifungals. At a therapeutically achievable concentration, lopinavir exhibited potent synergistic interactions with azole drugs, particularly with itraconazole against C. auris (fractional inhibitory concentration index [ΣFICI] ranged from 0.04 to 0.09). Additionally, the lopinavir/itraconazole combination enhanced the survival rate of C. auris-infected Caenorhabditis elegans by 90% and reduced the fungal burden in infected nematodes by 88.5% (P < 0.05) relative to that of the untreated control. Furthermore, lopinavir enhanced the antifungal activity of itraconazole against other medically important Candida species, including C. albicans, C. tropicalis, C. krusei, and C. parapsilosis Comparative transcriptomic profiling and mechanistic studies revealed that lopinavir was able to significantly interfere with the glucose permeation and ATP synthesis. This compromised the efflux ability of C. auris and consequently enhanced the susceptibility to azole drugs, as demonstrated by Nile red efflux assays. Altogether, these findings present lopinavir as a novel, potent, and broad-spectrum azole-chemosensitizing agent that warrants further investigation against recalcitrant Candida infections.
| S-EPMC7927799 | biostudies-literature