Anubhav Singh

Bio: Anubhav Singh is an academic researcher from University of Delhi. The author has contributed to research in topics: Candida auris. The author has an hindex of 1, co-authored 1 publications receiving 7 citations.

Colonisation and Transmission Dynamics of Candida auris among Chronic Respiratory Diseases Patients Hospitalised in a Chest Hospital, Delhi, India: A Comparative Analysis of Whole Genome Sequencing and Microsatellite Typing.

Abstract: Candida auris is a nosocomial pathogen responsible for an expanding global public health threat. This ascomycete yeast has been frequently isolated from hospital environments, representing a significant reservoir for transmission in healthcare settings. Here, we investigated the relationships among C. auris isolates from patients with chronic respiratory diseases admitted in a chest hospital and from their fomites, using whole-genome sequencing (WGS) and multilocus microsatellite genotyping. Overall, 37.5% (n = 12/32) patients developed colonisation by C. auris including 9.3% of the screened patients that were colonised at the time of admission and 75% remained colonised till discharge. Furthermore, 10% of fomite samples contained C. auris in rooms about 8.5 days after C. auris colonised patients were admitted. WGS and microsatellite typing revealed that multiple strains contaminated the fomites and colonised different body sites of patients. Notably, 37% of C. auris isolates were resistant to amphotericin B and a novel amino acid substitution, G145D in ERG2 gene, was detected in all amphotericin B resistant isolates. In addition, 55% of C. auris isolates had two copies of the MDR1 gene. Our results suggest significant genetic and ecological diversities of C. auris in healthcare setting. The WGS and microsatellite genotyping methods provided complementary results in genotype identification.

Candida auris: Epidemiology, Diagnosis, Pathogenesis, Antifungal Susceptibility, and Infection Control Measures to Combat the Spread of Infections in Healthcare Facilities

Abstract: Candida auris, a recently recognized, often multidrug-resistant yeast, has become a significant fungal pathogen due to its ability to cause invasive infections and outbreaks in healthcare facilities which have been difficult to control and treat. The extraordinary abilities of C. auris to easily contaminate the environment around colonized patients and persist for long periods have recently resulted in major outbreaks in many countries. C. auris resists elimination by robust cleaning and other decontamination procedures, likely due to the formation of ‘dry’ biofilms. Susceptible hospitalized patients, particularly those with multiple comorbidities in intensive care settings, acquire C. auris rather easily from close contact with C. auris-infected patients, their environment, or the equipment used on colonized patients, often with fatal consequences. This review highlights the lessons learned from recent studies on the epidemiology, diagnosis, pathogenesis, susceptibility, and molecular basis of resistance to antifungal drugs and infection control measures to combat the spread of C. auris infections in healthcare facilities. Particular emphasis is given to interventions aiming to prevent new infections in healthcare facilities, including the screening of susceptible patients for colonization; the cleaning and decontamination of the environment, equipment, and colonized patients; and successful approaches to identify and treat infected patients, particularly during outbreaks.

Genome-Wide Analysis of Experimentally Evolved Candida auris Reveals Multiple Novel Mechanisms of Multidrug Resistance.

Abstract: Candida auris is globally recognized as an opportunistic fungal pathogen of high concern, due to its extensive multidrug resistance (MDR) Still, molecular mechanisms of MDR are largely unexplored This is the first account of genome-wide evolution of MDR in C auris obtained through serial in vitro exposure to azoles, polyenes, and echinocandins We show the stepwise accumulation of copy number variations and novel mutations in genes both known and unknown in antifungal drug resistance Echinocandin resistance was accompanied by a codon deletion in FKS1 hot spot 1 and a substitution in FKS1 “novel” hot spot 3 Mutations in ERG3 and CIS2 further increased the echinocandin MIC Decreased azole susceptibility was linked to a mutation in transcription factor TAC1b and overexpression of the drug efflux pump Cdr1, a segmental duplication of chromosome 1 containing ERG11, and a whole chromosome 5 duplication, which contains TAC1b The latter was associated with increased expression of ERG11, TAC1b, and CDR2 but not CDR1 The simultaneous emergence of nonsense mutations in ERG3 and ERG11 was shown to decrease amphotericin B susceptibility, accompanied with fluconazole cross-resistance A mutation in MEC3, a gene mainly known for its role in DNA damage homeostasis, further increased the polyene MIC Overall, this study shows the alarming potential for and diversity of MDR development in C auris, even in a clade until now not associated with MDR (clade II), stressing its clinical importance and the urge for future research IMPORTANCECandida auris is a recently discovered human fungal pathogen and has shown an alarming potential for developing multi- and pan-resistance toward all classes of antifungals most commonly used in the clinic Currently, C auris has been globally recognized as a nosocomial pathogen of high concern due to this evolutionary potential So far, this is the first study in which the stepwise progression of multidrug resistance (MDR) in C auris is monitored in vitro Multiple novel mutations in known resistance genes and genes previously not or vaguely associated with drug resistance reveal rapid MDR evolution in a C auris clade II isolate Additionally, this study shows that in vitro experimental evolution can be a powerful tool to discover new drug resistance mechanisms, although it has its limitations

Molecular Epidemiological Investigation of a Nosocomial Cluster of C. auris : Evidence of Recent Emergence in Italy and Ease of Transmission during the COVID-19 Pandemic.

Abstract: Candida auris is an emerging MDR pathogen raising major concerns worldwide. In Italy, it was first and only identified in July 2019 in our hospital (San Martino Hospital, Genoa), where infection or colonization cases have been increasingly recognized during the following months. To gain insights into the introduction, transmission dynamics, and resistance traits of this fungal pathogen, consecutive C. auris isolates collected from July 2019 to May 2020 (n = 10) were subjected to whole-genome sequencing (WGS) and antifungal susceptibility testing (AST); patients' clinical and trace data were also collected. WGS resolved all isolates within the genetic clade I (South Asian) and showed that all but one were part of a cluster likely stemming from the index case. Phylogenetic molecular clock analyses predicted a recent introduction (May 2019) in the hospital setting and suggested that most transmissions were associated with a ward converted to a COVID-19-dedicated ICU during the pandemic. All isolates were resistant to amphotericin B, voriconazole, and fluconazole at high-level, owing to mutations in ERG11(K143R) and TACB1(A640V). Present data demonstrated that the introduction of MDR C. auris in Italy was a recent event and suggested that its spread could have been facilitated by the COVID-19 pandemic. Continued efforts to implement stringent infection prevention and control strategies are warranted to limit the spread of this emerging pathogen within the healthcare system.

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

Abstract: 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.

Candida auris on Apples: Diversity and Clinical Significance

Abstract: In 2019, the U.S. Centers for Disease Control and Prevention classified the multidrug-resistant Candida auris as one of five pathogens posing the most urgent threats to public health. ABSTRACT Candida auris is a multidrug-resistant nosocomial fungal pathogen. While the marine environment was recently identified as a natural niche for C. auris, the environment(s) that might have contributed to the development and spread of antifungal resistance in C. auris remains a mystery. Because stored fruits are often treated with fungicides to prevent postharvest spoilage, we hypothesized that stored fruits could serve as a possible selective force for and a transmission reservoir of antifungal-resistant isolates of pathogenic yeasts, including C. auris. To test this hypothesis, we screened fruits to study the diversity of pathogenic yeasts and their antifungal susceptibility profiles. Among the 62 screened apples, the surfaces of 8 were positive for C. auris, and all were stored apples. Whole-genome sequencing (WGS) showed that C. auris strains from apples were genetically diverse and exhibited broad phylogenetic distribution among the subclades within clade I. Interestingly, strains from apples had closely related strains from other sources in India, including from patients, hospitals, and marine environments, and from clinical strains from other parts of the world. A broad range of fungicides, including dimethyl inhibitors (DMIs), were detected in stored apples, and all C. auris isolates exhibited reduced sensitivity to DMIs. Interestingly, C. auris was not isolated from freshly picked apples. Together, the results suggest a potentially complex ecology for C. auris with agriculture fungicide application on stored fruits as a significant selective force for drug resistance in clinics. IMPORTANCE In 2019, the U.S. Centers for Disease Control and Prevention classified the multidrug-resistant Candida auris as one of five pathogens posing the most urgent threats to public health. At present, the environment(s) that might have contributed to the development and spread of antifungal resistance in C. auris is unknown. Here, we tested whether fruits could be a source of multidrug-resistant C. auris. We identified genetically diverse C. auris strains with reduced sensitivity to major triazole dimethyl inhibitors fungicides on the surfaces of stored apples. The successful isolation of C. auris from apples here calls for additional investigations into plants as a reservoir of C. auris. Our findings suggest that C. auris in the natural ecosystem may come in contact with agriculture fungicides and that stored fruits could be a significant niche for the selection of azole resistance in C. auris and other human fungal pathogens.