RESUMEN
Development of extensively drug resistant (XDR) strains and multidrug resistant (MDR) in Mycobacterium tuberculosis is caused by an efflux mechanism of antibiotics in the bacteria. Rv0191, predicted to a major facilitator superfamily transporter of efflux pump, contributes to elevated expression in some clinical isolates. To characterize the role of Rv0191 which might be involved in antibiotics resistance, Mycobacterium smegmatis was taken as a type strains to do drug susceptibility, ethidium bromide (EB) accumulation assay and electrophoretic mobility shift assay. M. smegmatis Ms0232 mutant became more susceptible to chloramphenicol and showed different cell surface properties. Rv1353c, a TetR family transcription factor, can downregulate the transcription of Rv0191. Rv1353c overexpression strain became more sensitive to chloramphenicol. Together, these findings indicate that Rv1353c encodes a transcriptional repressor that directly interacts with the Rv0191 promoter and modulates the expression of Rv0191. This provided a new player in mycobacteria chloramphenicol resistance.
Asunto(s)
Proteínas Bacterianas/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Mycobacterium tuberculosis/metabolismo , Proteínas Bacterianas/genética , Cloranfenicol/farmacocinética , Cloranfenicol/farmacología , Farmacorresistencia Bacteriana/genética , Regulación Bacteriana de la Expresión Génica , Técnicas de Inactivación de Genes , Genes Bacterianos , Humanos , Proteínas de Transporte de Membrana/genética , Mycobacterium smegmatis/efectos de los fármacos , Mycobacterium smegmatis/genética , Mycobacterium smegmatis/metabolismo , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Regiones Promotoras GenéticasRESUMEN
Due to environmental changes and manufacturing errors, uncertainties inherently exist in phononic crystals, especially in the material properties and geometric parameters. To handle the uncertainties with limited information, two different methods are proposed for band structure analysis of phononic crystals with uncertainties. One is the Monte Carlo method (MCM). The main shortcoming of it is the high computational cost. The other is the simplex Chebyshev polynomial expansion (SPCE) method. In addition, the computational efficiency of the SPCE method is much higher. In the SPCE method, the simplex Chebyshev is employed to estimate the band structures of phononic crystals. Meanwhile, the simplified incremental sampling strategy is introduced for the simplex Chebyshev to retain calculation accuracy and improve computational efficiency simultaneously. In the Chebyshev surrogate model, the samples yielded with the MCM are used to calculate the interval ranges of the band structures in phononic crystals. Three numerical examples, including a two-dimensional (2D) Helmholtz resonator phononic crystal, a 2D solid-solid phononic crystal, and a three-dimensional phononic crystal, are introduced to verify the effectiveness and efficiency of the proposed method.
RESUMEN
The increasing antibiotic resistance is now threatening to take us back to a pre-antibiotic era. Bacteria have evolved diverse resistance mechanisms, on which in-depth research could help the development of new strategies to control antibiotic-resistant infections. Epigenetic alterations and protein post-translational modifications (PTMs) play important roles in multiple cellular processes such as metabolism, signal transduction, protein degradation, DNA replication regulation and stress response. Recent studies demonstrated that epigenetics and PTMs also play vital roles in bacterial antibiotic resistance. In this review, we summarize the regulatory roles of epigenetic factors including DNA methylation and regulatory RNAs as well as PTMs such as phosphorylation and succinylation in bacterial antibiotic resistance, which may provide innovative perspectives on selecting antibacterial targets and developing antibiotics.