RESUMEN
INTRODUCTION: Candida auris is a globally disseminated invasive ascomycetous yeast, that imposes a substantial burden on healthcare systems. It has been documented to have spread to over 40 countries across six continents, necessitating in-depth comprehension through advanced techniques like Whole-Genome Sequencing. METHOD: This study entailed the isolation and Whole-Genome Sequencing of a fluconazole-resistant C. auris strain (CA01) obtained from a patient's blood in Beijing. Genome analysis was conducted to classify the strain, and molecular docking was performed to understand the impact of mutations on drug resistance. RESULTS: Genome analysis revealed that CA01 belongs to the South Asia Clade (I) and shares the closest genetic relationship with previously reported strains BJCA001 and BJCA002. Notably, unlike BJCA001, CA01 exhibits significant resistance to fluconazole primarily due to the A395T mutation in the ERG11 gene. Molecular docking studies demonstrated that this mutation leads to geometric changes in the active site where fluconazole binds, resulting in decreased binding affinity. Additionally, the present findings have identified several core virulence genes in C. auris, such as RBF1. DISCUSSION: The findings from this study expand the understanding of the genetic diversity and adaptive mechanisms of C. auris within the South Asia Clade (I). The observed fluconazole resistance driven by the ERG11 mutation A395T highlights the need for heightened awareness and adaptation in clinical treatment strategies in China. This study provides critical insights into drug resistance and virulence profiles at a genetic level, which could guide future therapeutic and management strategies for C. auris infections.
Asunto(s)
Antifúngicos , Candida auris , Farmacorresistencia Fúngica , Fluconazol , Humanos , Farmacorresistencia Fúngica/genética , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Fluconazol/farmacología , Fluconazol/uso terapéutico , Virulencia/genética , Candida auris/genética , Candida auris/efectos de los fármacos , Candida auris/patogenicidad , Pruebas de Sensibilidad Microbiana , Mutación , Beijing , Simulación del Acoplamiento Molecular , Candidiasis/microbiología , Candidiasis/tratamiento farmacológico , Secuenciación Completa del Genoma , Sur de AsiaRESUMEN
Abstract Objectives: the first five years of life are critical for children's physical and intellectual development. However, the under-five mortality rate in South Asia and ASEAN is relatively high, caused by complex etiologies. This paper identifies maternal high-risk fertility behaviors and healthcare services utilization and examines predictors of under-five mortality (U5M) in 7 Asian (South Asia - ASEAN) developing countries (Indonesia, Myanmar, Cambodia, Philippines, Bangladesh, Nepal, and Pakistan). Methods: a multivariate logistic regression model with a complex survey was used to examine predictors of U5M on the frequency of U5M adjusted for comorbidities. Results: according to multivariate models (model 2), U5M was 2.99 times higher in mothers with low weight at birth infants than in mothers without low weight at birth infants (aOR= 2.99; CI95%=2.49-3.58); Mothers without antenatal care contacts were 3.37 times more likely (aOR= 3.37; CI95%=2.83-4.00) to have a U5M than mothers with eight or more antenatal care contacts; U5M in Indonesia was 2.34 times higher (aOR= 2.34; CI95%= 1.89-2.89). It is investigated that antenatal care serves as a predictor in decreasing U5MR. Conclusions: in order to achieve significant U5MR reduction, intervention programs that encourage antenatal care consultations should be implemented.
Resumo Objetivos: os primeiros cinco anos de vida são críticos para o desenvolvimento físico e intelectual da criança. No entanto, a taxa de mortalidade de menores de cinco anos no sul da Ásia e na ASEAN é relativamente alta, causada por etiologias complexas. Este artigo identifica comportamentos maternos de fertilidade de alto risco e utilização de serviços de saúde e examina preditores de mortalidade abaixo de 5 anos (MM5) em 7 países em desenvolvimento da Ásia (Sul da Ásia - ASEAN) (Indonésia, Mianmar, Camboja, Filipinas, Bangladesh, Nepal e Paquistão). Métodos: um modelo de regressão logística multivariada foi usado para examinar preditores de MM5 na frequência de MM5 ajustado para comorbidades. Resultados: na análise multivariada (modelo 2), U5M foi 2,99 vezes maior em mães com bebês com baixo peso ao nascer do que em mães sem bebês com baixo peso ao nascer (aOR= 2,99; IC95%=2,49-3,58); as mães sem contatos de cuidados pré-natais tiveram 3,37 vezes mais probabilidade (aOR=3,37; IC95%=2,83-4,00) para ter MM5 do que mães com oito ou mais contatos de cuidados pré-natais; MM5 na Indonésia foi 2,34 vezes maior (aOR= 2,34; IC95%= 1,89-2,89). Investiga-se que os cuidados pré-natais funcionam como um preditor na diminuição da MM5. Conclusões: para uma redução significativa da MM5, devem ser implementados programas de intervenção que estimulem as consultas pré-natais.