Mutations in rpoB and katG genes and the inhA operon in multidrug-resistant Mycobacterium tuberculosis isolates from Zambia

Solo, Eddie Samuneti; Nakajima, Chie; Kaile, Trevor; Bwalya, Precious; Mbulo, Grace; Fukushima, Yukari; Chila, Sylvia; Kapata, Nathan; Shah, Yogendra; Suzuki, Yasuhiko

doi:10.1016/j.jgar.2020.02.026

Cited by 18 publications

(29 citation statements)

References 33 publications

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“…Regarding INH resistance-conferring mutations, all isolates except one carried a mutation at codon Ser315 in katG, and the majority (136/139) was Ser315Thr. Two isolates had a mutation in the inhA promoter region (C-15 T) (Solo et al, 2020).…”

Section: Frequencies Of Drug Resistance-conferring Mutations Among Mmentioning

confidence: 99%

Characterization of Mycobacterium tuberculosis genotypes and their correlation to multidrug resistance in Lusaka, Zambia

Solo

Suzuki

Kaile

et al. 2021

International Journal of Infectious Diseases

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The burden of multidrug-resistant tuberculosis (MDR-TB) has been reported to be increasing in Zambia. The reasons for the increase are still unclear. This study determined the diversity of Mycobacterium tuberculosis genotypes among isolates in Lusaka, the capital city, and investigated their association with MDR-TB. Methods: Spoligotyping, large sequence polymorphism (LSP) analysis, and sequencing of MDR associated genes were performed on a total of 274 M. tuberculosis clinical isolates stored at the University Teaching Hospital from 2013 to 2017. Of these, 134 were MDR-TB while 126 were pan-susceptible. Results: Spoligotyping showed the LAM family as the most predominant genotype (149/274, 54.4%) followed by the CAS family (44/274, 16.1%), T family (39/274, 14.2%), and minor proportions of X, S, Harleem, EAI and Beijing spoligofamilies were identified. Three M. bovis isolates were also observed. Among those, CAS1-Kili (SIT 21) and LAM1 (SIT 20) subfamilies showed a propensity for MDR-TB with p = 0.0001 and p = 0.001, respectively. Conclusions: This phenomenon might explain the future increase in the MDR-TB burden caused by specific lineages in Zambia. Therefore, it is recommended that the National TB control program in the country complements conventional control strategies with molecular analysis for monitoring and surveillance of MDR-TB epidemiology.

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Section: Frequencies Of Drug Resistance-conferring Mutations Among Mmentioning

confidence: 99%

Characterization of Mycobacterium tuberculosis genotypes and their correlation to multidrug resistance in Lusaka, Zambia

Solo

Suzuki

Kaile

et al. 2021

International Journal of Infectious Diseases

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“…This practice could have led to the undetected emergence and silent spread of drug-resistant TB. In a previous study, it was demonstrated that the increase in MDR-TB in Zambia is not the result of transborder transmission but local emergence and possible spread within Zambia [4,5]. The mismanagement of MDR-TB could further the evolution of resistance to other anti-TB drugs.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Mutations Associated with Streptomycin Resistance in Multidrug-Resistant Mycobacterium tuberculosis in Zambia

et al. 2021

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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.

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“…resistant MTB strains that are often resistant even to other drugs (5,21). Furthermore, studies have indicated a high prevalence of MDR-MTB carrying this mutation of katG 315 (AGC > ACC) from some high TB burden countries such as Bangladesh (80%) (22), Russian Federation (93%) (23), South Africa (87%) (24), and Zambia (91%) (25).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Rapid and Simple Detection of Isoniazid-Resistant <i>Mycobacterium tuberculosis</i> Utilizing a DNA Chromatography-Based Technique

Kodera¹,

Yamaguchi

Fukushima

et al. 2021

Jpn J Infect Dis

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Mutations in rpoB and katG genes and the inhA operon in multidrug-resistant Mycobacterium tuberculosis isolates from Zambia

Cited by 18 publications

References 33 publications

Characterization of Mycobacterium tuberculosis genotypes and their correlation to multidrug resistance in Lusaka, Zambia

Characterization of Mycobacterium tuberculosis genotypes and their correlation to multidrug resistance in Lusaka, Zambia

Characterization of Mutations Associated with Streptomycin Resistance in Multidrug-Resistant Mycobacterium tuberculosis in Zambia

Rapid and Simple Detection of Isoniazid-Resistant <i>Mycobacterium tuberculosis</i> Utilizing a DNA Chromatography-Based Technique

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