Detecting Ethambutol Resistance in Mycobacterium tuberculosis Isolates in China: A Comparison Between Phenotypic Drug Susceptibility Testing Methods and DNA Sequencing of embAB
FRONTIERS IN MICROBIOLOGY
Authors: Li, Ma-chao; Chen, Rong; Lin, Shi-qiang; Lu, Yao; Liu, Hai-can; Li, Gui-lian; Liu, Zhi-guang; Zhao, Xiu-qin; Zhao, Li-li; Wan, Kang-Lin
With the increasing incidence of drug-resistant tuberculosis (DR-TB), determining a rapid and accurate drug susceptibility testing (DST) method to identify ethambutol (EMB) resistance in Mycobacterium tuberculosis has become essential for patient management in China. Herein, we evaluated the correlation between three phenotypic DST methods, namely, proportion method (PM), MGIT 960 system, and microplate alamar Blue assay (MABA), and DNA sequencing of embAB in 118 M. tuberculosis isolates from China. When the results of the phenotypic DST methods were compared with those of DNA sequencing, the overall agreement and kappa values of the PM, MGIT 960 system, and MABA were 81.4% and 0.61, 77.1% and 0.55, and 84.7% and 0.67, respectively. The agreement for EMB resistance between MABA and PM was significantly higher than that between the MGIT 960 system and PM (P = 0.02). Moreover, among the isolates with detectable embAB mutations, 97.2% (70/72 isolates) harbored mutations in embB. The analysis of embB mutations predicted EMB resistance with 81.3% sensitivity, 86.8% specificity, and 83.1% accuracy. Thus, MABA may be a better phenotypic DST method for detecting EMB resistance. DNA sequencing of embB may be useful for the early identification of EMB resistance and the consequent optimization of the treatment regimen.
Transcriptomic dataset of Mycolicibacterium smegmatis exposed to an imidazo[1,2-b][1,2,4,5]tetrazine
DATA IN BRIEF
Authors: Vatlin, Aleksey A.; Klimina, Ksenia M.; Frolova, Svetlana G.; Danilenko, Valery N.; Maslov, Dmitry A.
Deciphering the mechanism of action of novel antituberculosis compounds is a key step in the drug development process. We have previously described a number of imidazo[1,2b][1,2,4,5]tetrazines with a promising activity on Mycobacterium tuberculosis  . These compounds had predicted activity as serine-threonine protein kinase inhibitors, however spontaneous drug resistant Mycolicibacterium smegmatis mc(2) 155 (formerly Mycobacterium smegmatis) revealed only the mycobacterial mechanism of resistance to imidazo[1,2b][1,2,4,5]tetrazines: mutations in MSMEG_1380 gene lead to overexpression of the mmpS5-mmpL5 operon in M. smegmatis, thus providing resistance to imidazo[1,2b][1,2,4,5]tetrazines via enhanced efflux  . Here we report the RNA sequencing data of M. smegma tis mc(2) 155 culture treated with one of the imidazo[1,2b][1,2,4,5]tetrazines for 1.5 h and the untreated culture as a control. The mapped reads showed that a total of 1386 genes are differentially expressed in this experiment. A further analysis of these data can shed light of the mechanism of action of imidazo[1,2-b][1,2,4,5]tetrazines. The data gener-ated by RNA-seq (raw reads) have been deposited to NCBI sequence read archive (SRA) and have been assigned a Bio-Project accession number PRJNA615922. (C) 2020 The Author(s). Published by Elsevier Inc.