TY - JOUR
T1 - Characterization of mutations associated with streptomycin resistance in multidrug-resistant mycobacterium tuberculosis in zambia
AU - Bwalya, Precious
AU - Yamaguchi, Tomoyuki
AU - Solo, Eddie Samuneti
AU - Chizimu, Joseph Yamweka
AU - Mbulo, Grace
AU - Nakajima, Chie
AU - Suzuki, Yasuhiko
N1 - Funding Information:
Funding: This research was funded by a grant from the Ministry of Education, Culture, Sports, Science, and Technology (MEXT), Japan for the Joint Research Program of Hokkaido University International Institute for Zoonosis Control to Y.S., and in part by Japan Agency for Medical Research and Development (AMED) under Grant Number JP20jk0210005, JP20jm0110021, and JP21wm0125008 to Y.S.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/10
Y1 - 2021/10
N2 - Streptomycin (STR) is recommended for the management of multidrug-resistant tuberculosis (MDR-TB). Streptomycin resistance-conferring mutation types and frequency are shown to be influenced by genotypes of circulating strains in a population. This study aimed to characterize the mutations in MDR-TB isolates and examine their relationship with the genotypes in Zambia. A total of 138 MDR-TB isolates stored at the University Teaching Hospital Tuberculosis Reference Laboratory in Zambia were analyzed using spoligotyping and sequencing of STR resistance-associated genes. Streptomycin resistance was observed in 65.9% (91/138) of MDR-TB isolates. Mutations in rpsL, rrs, and gidB accounted for 33%, 12.1%, and 49.5%, respectively. Amino acid substitution K43R in rpsL was strongly associated with the CAS1_Kili genotype (p < 0.0001). The combination of three genes could predict 91.2% of STR resistance. Clustering of isolates based on resistance-conferring mutations and spoligotyping was observed. The clustering of isolates suggests that the increase in STR-resistant MDR-TB in Zambia is largely due to the spread of resistant strains from inadequate treatment. Therefore, rapid detection of STR resistance genetically is recommended before its use in MDR-TB treatment in Zambia.
AB - Streptomycin (STR) is recommended for the management of multidrug-resistant tuberculosis (MDR-TB). Streptomycin resistance-conferring mutation types and frequency are shown to be influenced by genotypes of circulating strains in a population. This study aimed to characterize the mutations in MDR-TB isolates and examine their relationship with the genotypes in Zambia. A total of 138 MDR-TB isolates stored at the University Teaching Hospital Tuberculosis Reference Laboratory in Zambia were analyzed using spoligotyping and sequencing of STR resistance-associated genes. Streptomycin resistance was observed in 65.9% (91/138) of MDR-TB isolates. Mutations in rpsL, rrs, and gidB accounted for 33%, 12.1%, and 49.5%, respectively. Amino acid substitution K43R in rpsL was strongly associated with the CAS1_Kili genotype (p < 0.0001). The combination of three genes could predict 91.2% of STR resistance. Clustering of isolates based on resistance-conferring mutations and spoligotyping was observed. The clustering of isolates suggests that the increase in STR-resistant MDR-TB in Zambia is largely due to the spread of resistant strains from inadequate treatment. Therefore, rapid detection of STR resistance genetically is recommended before its use in MDR-TB treatment in Zambia.
KW - Multidrug-resistant tuberculosis (MDR-TB)
KW - Mycobacterium tuberculosis
KW - Spoligotype
KW - Streptomycin
KW - Zambia
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U2 - 10.3390/antibiotics10101169
DO - 10.3390/antibiotics10101169
M3 - Article
AN - SCOPUS:85116018667
SN - 2079-6382
VL - 10
JO - Antibiotics
JF - Antibiotics
IS - 10
M1 - 1169
ER -
