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'Candida' species are major fungal pathogens in humans. The aim of this study was to determine the prevalence of individual 'Candida' species and their susceptibility to antifungal drugs among clinical isolates in a tertiary care hospital in Bangladesh. During a 10-month period in 2021, high vaginal swabs (HVSs), blood, and aural swabs were collected from 360 patients. From these specimens, 'Candida' spp. was isolated from cultures on Sabouraud dextrose agar media, and phenotypic and genetic analyses were performed. A total of 109 isolates were recovered, and C. albicans accounted for 37%, being derived mostly from HVSs. Among non-albicans 'Candida' (NAC), C. parapsilosis was the most frequent, followed by 'C. ciferrii', 'C. tropicalis', and 'C. glabrata'. Three isolates from blood and two isolates from aural discharge were genetically identified as 'C. auris' and 'Kodamaea ohmeri', respectively. NAC isolates were more resistant to fluconazole (overall rate, 29%) than 'C. albicans' (10%). 'Candida' isolates from blood showed 95% susceptibility to voriconazole and less susceptibility to fluconazole (67%). Two or three amino acid substitutions were detected in the ERG11 of two fluconazole-resistant 'C. albicans' isolates. The present study is the first to reveal the prevalence of 'Candida' species and their antifungal susceptibility in Bangladesh.

is an emerging multidrug-resistant fungal pathogen that poses a significant global health threat. Since its discovery in 2009, has rapidly spread worldwide, causing severe infections with high mortality rates, particularly in healthcare settings. Its ability to persist in the environment, form biofilms, and resist multiple antifungal drugs underscores the urgent need to understand its pathogenicity mechanisms and associated signaling pathways. Such insights are crucial for elucidating its unique virulence traits and developing targeted therapeutic strategies. Current studies have identified several key pathways involved in its pathogenicity and antifungal drug resistance. The Ras/cAMP/PKA pathway regulates critical virulence factors, including thermotolerance, morphological plasticity, and biofilm formation. The mitogen-activated protein kinase (MAPK) and calcineurin pathways contribute to stress responses and antifungal drug resistance. The regulation of Ace2 and morphogenesis (RAM) pathway influences cell aggregation, while the target of rapamycin (TOR) pathway affects filamentous growth and biofilm development. However, the distinct characteristics of , such as its rapid environmental spread and clade-specific traits, warrant further investigation into additional signaling pathways. This review provides a comprehensive analysis of known signaling pathways associated with pathogenicity and antifungal drug resistance, integrating insights from other fungal pathogens. By synthesizing current knowledge and identifying research gaps, this review offers new perspectives on future research directions and potential therapeutic targets against this formidable pathogen.

Despite the recently growing concern of pan-resistant Candida auris infection, the pathogenicity of this ascomycetous fungal pathogen and the signaling circuitries governing its resistance to antifungal drugs are largely unknown. Therefore, we analyzed the pathobiological functions of cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway in C. auris , which plays conserved roles in the growth and virulence of fungal pathogens. Candida auris is a globally emerging multidrug-resistant fungal pathogen. Its pathogenicity-related signaling networks are largely unknown. Here, we characterized the pathobiological functions of the cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway in C. auris . We focused on adenylyl cyclase ( CYR1 ), the PKA regulatory subunit ( BCY1 ), and the PKA catalytic subunits ( TPK1 and TPK2 ). We concluded that PKA acts both dependently and independently of Cyr1 in C. auris . Tpk1 and Tpk2 have major and minor roles, respectively, in PKA activity and functions. Both Cyr1 and PKA promote growth, thermotolerance, filamentous growth, and resistance to stress and antifungal drugs by regulating expression of multiple effector genes. In addition, Cyr1 and PKA subunits were involved in disinfectant resistance of C. auris . However, deletion of both TPK1 and TPK2 generally resulted in more severe defects than CYR1 deletion, indicating that Cyr1 and PKA play redundant and distinct roles. Notably, Tpk1 and Tpk2 have redundant but Cyr1-independent roles in haploid-to-diploid cell transition, which increases virulence of C. auris . However, Tpk1 and Tpk2 often play opposing roles in formation of biofilms and the cell wall components chitin and chitosan. Surprisingly, deletion of CYR1 or TPK1/TPK2 , which resulted in severe in vitro growth defects at 37°C, did not attenuate virulence, and BCY1 deletion reduced virulence of C. auris in a systemic murine infection model. In conclusion, this study provides comprehensive insights into the role of the cAMP/PKA pathway in drug resistance and pathogenicity of C. auris and suggests a potential therapeutic option for treatment of C. auris - mediated candidemia. IMPORTANCE Despite the recently growing concern of pan-resistant Candida auris infection, the pathogenicity of this ascomycetous fungal pathogen and the signaling circuitries governing its resistance to antifungal drugs are largely unknown. Therefore, we analyzed the pathobiological functions of cyclic AMP (cAMP)/protein kinase A (PKA) signaling pathway in C. auris , which plays conserved roles in the growth and virulence of fungal pathogens. We show that adenylyl cyclase Cyr1 and PKA have pleiotropic roles in growth, morphogenesis, stress responses, antifungal drug and disinfectant resistance, and ploidy shifts of C. auris . Notably, however, we observed that the tpk1 Δ tpk2 Δ mutant generally exhibited more disrupted phenotypes than the cyr1 Δ mutant, and we suggest Tpk1 and Tpk2 have both cAMP-dependent and -independent roles in this pathogen. Most surprisingly, we observed that hyperactivation, not inhibition, of the cAMP/PKA pathway reduced virulence of C. auris . Based on our results, we suggest and discuss potential therapeutic strategies for candidiasis caused by C. auris .

Objectives To investigate the clinical relevance, origin, transmission, and resistance of Candida auris ( C. auris ) isolates from two outbreaks and sporadic occurrences from one hospital in China. Methods A total of 135 C. auris isolates were collected. Clinical characteristics were obtained and antifungal susceptibility testing (AFST) was performed using the method of broth microdilution. Phylogenetic tree, WGS analysis, and single nucleotide polymorphisms (SNPs) were used to determine the origin, transmission, and resistance mechanisms. Results A total of 31 patients (91.2%, 31/34) received invasive medical procedures and 13 patients (38.2%, 13/34) had antifungal agents before C. auris infection/colonization, except one patient whose clinical information was missing. Only 4 cases of C. auris candidemia were observed. 18 patients died, 13 patients recovered, and the outcomes of 3 patients were not available. A total of 35 C. auris isolates, which were successfully cultivated and the first isolated or harbored specific drug-resistant phenotype from each patient, were selected to be sequenced and further analyzed. C. auris isolates presented low genetic variability and belonged to clade I, possibly originating from BJ004-H7 in Beijing. All 35 isolates were resistant to Fluconazole (FCZ) and amphotericin B (AMB), and 3 isolates were resistant to caspofungin (CAS). Mutations in ERG11 and FKS1 were linked to reduced azole and echinocandin susceptibility, respectively. Conclusions Two outbreaks of highly clonal, multidrug-resistant C. auris isolates within the medical facility were reported. The intensive performance of disinfection measures helped block in-hospital transmission. Understanding the epidemiology, drug resistance and management of C. auris will be helpful for implementing effective infection control and treatment strategies. Highlight Two outbreaks and sporadic occurrences of C. auris from one hospital in China. Multidrug-resistant C. auris to ≥ 3 drug class (azole, amphotericin B, and echinocandin) was reported. Intensive performance of disinfection measures helped block in-hospital transmission of C. auris .

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. 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.

BackgroundCandida auris (C. auris) is an emerging aggressive pathogen that causes severe infections in critically ill patients. Therefore, the assessment of this pathogen, characterized by inclination for biofilm formation, elevated colonization rate, and resistance to multiple drugs, holds a paramount importance. There is no data regarding the isolation of C. auris in our tertiary care hospitals’ intensive care units (ICUs). The current case study was arranged to assess the incidence of C. auris central line-associated bloodstream infection (CLABSI) problem in our (ICUs).MethodsSpecimens of central venous catheter blood, peripheral blood, and catheter tips were collected from 301 critically ill patients with suspected (CLABSI). Microbiological cultures were utilized to diagnose bacterial and fungal superinfections. The fungal species identification and antifungal susceptibility testing were conducted using the Brilliance Chrome agar, VITEK® 2 compact system, and MALDI-TOF MS.ResultsAll included specimens (100%) yielded significant growth. Only 14 specimens (4.7%) showed fungal growth in the form of different Candida species. When comparing the identification of C. auris, MALDI-TOF MS is considered the most reliable method. Brilliance CHROMagar demonstrated a sensitivity of 100%, whereas VITEK only showed a sensitivity of approximately 33%. All recovered isolates of C. auris were fluconazole resistant.ConclusionC. auris is a highly resistant emerging pathogen in our ICUs that is often overlooked in identification using conventional methods.

Background The difficulties in the identification of C. auris and the delays in the implementation of infection control precautions contribute to outbreaks. This study analyzed 10 patients with COVID-19 and C. auris candidemia, their characteristic and clinical features and phylogenetic features, and the antifungal susceptibilities of the isolates. Method C. auris were detected in the COVID-19 ICU of a university hospital between January and August 2021. Identification to species level was performed using MALDI-TOF MS. Antifungal susceptibilities were determined by the Sensititre YeastOne YO10 panel. The isolates were whole genome sequenced to assess genetic relatedness and a phylogenetic tree was drawn including various C. auris clades. Results The mean growth time in blood cultures was 38.8 h. C. auris candidemia developed on the average 27th day of ICU admission. All were susceptible to anidulafungin and micafungin, while they were resistant to fluconazole and amphotericin B. Only three isolates were found to be resistant to caspofungin. All patients died. With the WGS method, all isolates were found in a close resemblance to each other in terms of total nucleotide similarity (with a minimum of 96% pairwise alignment). Our isolates showed the closest similarity to South Asian clade (Clade I). Conclusions This study is the first to evaluate the phylogenetic characteristics of C. auris using WGS and to determine antifungal susceptibilities in Türkiye on COVID-19 patients. The mortality rate was very high in patients who have both COVID-19 and C. auris candidemia.

Candidozyma auris is a global human health threat because of its near-universal resistance to the antifungal fluconazole as well as a predisposition to multidrug resistance among clinical isolates. The underlying mechanisms of antifungal drug resistance in this species are still largely under investigation, and these efforts are significantly supported by research that increase our understanding of unique aspects of C. auris biology. We have identified a correlation between C. auris isolates’ susceptibility to fluconazole and intracellular drug accumulation in which drug-resistant isolates have significantly reduced intracellular fluconazole compared to isolates that are susceptible to fluconazole. We have proposed a mechanism for this phenomenon and demonstrated important roles for mutations in ERG11, TAC1B, and CDR1 gene sequences for drug resistance.

Candida auris is an emerging pathogen and human health threat. However, diagnosis and treatment of fungal infection due to C. auris are challenging. This narrative review provides a focused overview of C. auris for the emergency clinician. C. auris was first identified in 2009 and is currently present on all continents except Antarctica. C. auris possesses multiple genetic factors resulting in antimicrobial resistance, increased virulence and survival within the host, and environmental adaptation. It is readily transmitted from person to person and from the environment to a person, resulting in colonization. Infection may develop days to months following colonization, most commonly in those with immunocompromised state, significant comorbidities or other underlying conditions, healthcare exposure, and recent antimicrobial therapy. Candidemia, device infection (e.g., central venous catheter), soft tissue or wound infection, burn infection, osteomyelitis, myocarditis, meningitis, and urinary tract infection have been associated with C. auris. Samples should be obtained from the suspected site of infection for microbiological culture. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with reference databases to differentiate C. auris from other species is optimal for diagnosis, though other molecular testing methods are available. Treatment is challenging due to antifungal resistance, with over 90% resistant to fluconazole. Echinocandins are most commonly used as the first line therapy. Prevention of colonization and infection are vital and include screening in high-risk populations and strict adherence to infection prevention practices with contact precautions and hand hygiene, as well as appropriate decontamination of patient areas. An understanding of C. auris can assist emergency clinicians in the care of infected or colonized patients.