RESUMEN
Objectives: Clarithromycin is recommended as the core agent for treating M. abscessus infections, which usually calls for at least one year of treatment course, facilitating the development of resistance. This study aimed to identify the underlying mechanism of in vivo development of clarithromycin resistance in M. abscessus clinical isolates. Methods: M. abscessus isolates from patients with lung infections during long-term antibiotic therapy were longitudinally collected and sequenced. PFGE DNA fingerprinting was used to confirm the genetic relationships of the isolates. Whole genome comparative analysis was performed to identify the genetic determinants that confer the clarithromycin resistance. Results: Three pairs of initially clarithromycin-susceptible and subsequently clarithromycin-resistant M. abscessus isolates were obtained. We found that the clarithromycin-resistant isolates emerged relatively rapidly, after 4-16 months of antibiotic therapy. PFGE DNA fingerprinting showed that the clarithromycin-resistant isolates were identical to the initial clarithromycin-susceptible ones. Whole genome sequencing and bioinformatics analysis identified several genetic alternations in clarithromycin-resistant isolates, including genes encoding efflux pump/transporter, integral component of membrane, and the tetR and lysR family transcriptional regulators. Conclusion: We identified genes likely encoding new factors contributing to clarithromycin-resistance phenotype of M. abscessus, which can be useful in prediction of clarithromycin resistance in M. abscessus.
Asunto(s)
Claritromicina/uso terapéutico , ADN Bacteriano , Farmacorresistencia Bacteriana , Infecciones por Mycobacterium no Tuberculosas , Mycobacterium abscessus , Antibacterianos/uso terapéutico , Biología Computacional , Dermatoglifia del ADN/métodos , Análisis Mutacional de ADN/métodos , ADN Bacteriano/análisis , ADN Bacteriano/genética , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Regulación Bacteriana de la Expresión Génica , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones por Mycobacterium no Tuberculosas/tratamiento farmacológico , Infecciones por Mycobacterium no Tuberculosas/microbiología , Mycobacterium abscessus/efectos de los fármacos , Mycobacterium abscessus/genética , Mycobacterium abscessus/aislamiento & purificación , Tiempo , Secuenciación Completa del GenomaRESUMEN
OBJECTIVE: To investigate the effect of gastrodine on the expression of NR1 mRNA of NMDA receptor in cultured rat cerebral cortical neurons injury induced by hypoxia. METHOD: The injury models of cultured rat cerebral cortical neurons was made by hypoxia and hypoglucose. The concentration of 13, 26, 52 mg x L(-1) of gastrodine was respectively added to the injured cells. The R-PCR technique was used to study the expression of NR1 mRNA of NMDA receptor. RESULT: The expression of NR1 mRNA increased markedly in hypoxia and hypoglucose injured cells, the increased expression can be weakened by gastrodine, more significant effect was found in the concentration of 26 mg x L(-1) 52 mg x L(-1). CONCLUSION: Gastrodine may act as a neuro - protector by weakening the expression of NR1 mRNA in cultured rat cerebral cortical neurons injury induced by hypoxia and hypoglucose.