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The roles of rpsL, rrs, and gidB mutations in predicting streptomycin-resistant drugs used on clinical Mycobacterium tuberculosis isolates from Hebei Province, China.

ABSTRACT: Streptomycin (STR) is a component of first-line drugs used to treat multidrug-resistant tuberculosis. The purpose of this study was to investigate the proportion and type of mutations in Mycobacterium tuberculosis isolates resistant to STR and their relationship with the STR-resistant phenotype and with the epidemiological molecular model of the isolates. A total of 302 clinical isolates, including 215 STR-resistant and 87 STR-susceptible isolates, were characterized using the proportion method with Lowenstein-Jensen medium. The genes rpsL, rrs and gidB were screened for mutations using DNA sequencing methodology. All strains were genotyped using the spoligotyping technique. Mutations in rpsL and in rrs were observed in 63.3% and 15.8% of the STR-resistance isolates, respectively. The most prevalent mutations were the Lys43Arg substitution in the rpsL gene and the A514C change in the rrs gene. Ten novel mutations were identified in gidB. These novel mutations might be new potential markers for predicting STR-resistance in clinical Mycobacterium tuberculosis isolates. Mutations in rpsL, rrs, and gidB had a sensitivity of 84.2% and a specificity of 77.0% for the detection of STR-resistance isolates. The Beijing lineage strains were associated with the rpsL mutation Lys43Arg (P = 0.051), as well as the dual gidB mutations Glu92Asp and Ala205Ala (P < 0.001). Our study suggested that rpsL and rrs can act as useful genetic markers for predicting STR-resistance, and gidB polymorphisms play an important role in STR-resistant clinical Mycobacterium tuberculosis isolates from Hebei, China.

SUBMITTER: Wang Y

PROVIDER: S-EPMC6949554 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The roles of rpsL, rrs, and gidB mutations in predicting streptomycin-resistant drugs used on clinical Mycobacterium tuberculosis isolates from Hebei Province, China.

Wang Yuling Y Li Qianlin Q Gao Huixia H Zhang Zhi Z Liu Yuzhen Y Lu Jianhua J Dai Erhei E

International journal of clinical and experimental pathology 20190701 7

Streptomycin (STR) is a component of first-line drugs used to treat multidrug-resistant tuberculosis. The purpose of this study was to investigate the proportion and type of mutations in Mycobacterium tuberculosis isolates resistant to STR and their relationship with the STR-resistant phenotype and with the epidemiological molecular model of the isolates. A total of 302 clinical isolates, including 215 STR-resistant and 87 STR-susceptible isolates, were characterized using the proportion ...[more]

PMID: 31934102

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Project description:BACKGROUND:Streptomycin (SM) is a broad spectrum antibiotic and is an important component of any anti-tuberculosis therapy regimen. Several mechanisms have been proposed to explain the emergence of resistance but still our knowledge is inadequate. Proteins form a very complex network and drugs are countered by their modification/efflux or over expression/modification of targets. As proteins manifest most of the biological processes, these are attractive targets for developing drugs, immunodiagnostics or therapeutics. The aim of present study was to analyze and compare the protein profile of whole cell extracts from Mycobacterium tuberculosis clinical isolates susceptible and resistant to SM. RESULTS:Two-dimensional gel electrophoresis (2DE) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry was employed for analyzing the protein profiles. Homology and in silico characterization for identified proteins was assessed using BLAST, InterProScan and KEGG database searches. Computational studies on the possible interactions between SM and identified proteins were carried out by a battery of online servers and softwares, namely, CLUSTALW (KEGG), I-TASSER, VMD, PatchDock and FireDock. On comparing 2DE patterns, nine proteins were found consistently overexpressed in SM resistant isolates and were identified as Rv0350, Rv0440, Rv1240, Rv3075c, Rv2971, Rv3028c, Rv2145c, Rv2031c and Rv0569. In silico docking analysis showed significant interactions of SM with essential (Rv0350, Rv0440 and Rv2971) and non essential (Rv1240, Rv3075c and Rv2031c) genes. CONCLUSIONS:The computational results suggest high protein binding affinity of SM and suggested many possible interactions between identified proteins and the drug. Bioinformatic analysis proves attributive for analysis of diversity of proteins identified by whole proteome analysis. In-depth study of the these proteins will give an insight into probable sites of drug action other than established primary sites and hence may help in search of novel chemotherapeutic agents at these new sites as inhibitors.

Dataset Information

The roles of rpsL, rrs, and gidB mutations in predicting streptomycin-resistant drugs used on clinical Mycobacterium tuberculosis isolates from Hebei Province, China.

Publications

The roles of <i>rpsL</i>, <i>rrs</i>, and <i>gidB</i> mutations in predicting streptomycin-resistant drugs used on clinical <i>Mycobacterium tuberculosis</i> isolates from Hebei Province, China.

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