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

Yuling Wang; Qianlin Li; Huixia Gao; Zhi Zhang; Yuzhen Liu; Jianhua Lu; Erhei Dai

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

Int J Clin Exp Pathol. 2019 Jul 1;12(7):2713-2721. eCollection 2019.

Authors

Yuling Wang¹, Qianlin Li², Huixia Gao³, Zhi Zhang³, Yuzhen Liu³, Jianhua Lu³, Erhei Dai³

Affiliations

¹ Department of Tuberculosis, The Fifth Affiliated Hospital of Shijiazhuang, North China University of Science and Technology Shijiazhuang 050021, Hebei, China.
² Department of Epidemiology and Statistics, North China University of Science and Technology Tangshan 063210, Hebei, China.
³ Department of Laboratory Medicine, The Fifth Affiliated Hospital of Shijiazhuang, North China University of Science and Technology Shijiazhuang 050021, Hebei, China.

PMID: 31934102
PMCID: PMC6949554

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.

Keywords: Mycobacterium tuberculosis; Spoligotyping; gene mutation; streptomycin.