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

Bwalya, Precious; Yamaguchi, Tomoyuki; Solo, Eddie Samuneti; Chizimu, Joseph Yamweka; Mbulo, Grace; Nakajima, Chie; Suzuki, Yasuhiko

doi:10.3390/antibiotics10101169

Cited by 14 publications

(8 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Phenotypic streptomycin resistance is explained by mutations in rpsL, rrs , and gidB . 13 In the present study, we found that the common mutations that conferred resistance to streptomycin were rpsL K43R and rrs A514C, excluding gidB , similar to that reported previously. 13 Phenotypic resistance to second-line injectables (amikacin, kanamycin, and capreomycin) can be caused by mutations in the rrs gene, tlyA gene, and eis promoter.…”

Section: Discussionsupporting

confidence: 91%

“… 13 In the present study, we found that the common mutations that conferred resistance to streptomycin were rpsL K43R and rrs A514C, excluding gidB , similar to that reported previously. 13 Phenotypic resistance to second-line injectables (amikacin, kanamycin, and capreomycin) can be caused by mutations in the rrs gene, tlyA gene, and eis promoter. 24 In the present study, among the two second-line injectable-resistant M. tuberculosis strains, only one strain (strain 86) had mutation A1401G in rrs , whereas the other did not, suggesting that this mutation may not be enough to explain phenotypic resistance to second-line injectables.…”

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

Characterization of Fluoroquinolone-Resistant and Multidrug-Resistant Mycobacterium tuberculosis Isolates Using Whole-Genome Sequencing in Tianjin, China

Wang¹,

Sun²,

Mu³

et al. 2022

IDR

View full text Add to dashboard Cite

Objective Tuberculosis (TB) caused by Mycobacterium tuberculosis remains a global concern. This study aimed to determine the molecular characteristics of fluoroquinolone-resistant and multidrug-resistant M. tuberculosis strains using whole-genome sequencing to predict drug resistance in M. tuberculosis in Tianjin, China, which has not been established previously. Methods Twenty-one fluoroquinolone-resistant and multidrug-resistant M. tuberculosis strains were isolated from sputum samples. Phenotypic drug resistance against 12 anti-tuberculosis drugs was determined using drug susceptibility testing. Whole-genome sequencing was performed to predict drug resistance in M. tuberculosis based on genome regions associated with drug resistance. The sensitivity of whole-genome sequencing for predicting drug resistance was calculated based on phenotypic drug susceptibility testing information. Results Among the 21 isolates, mutations in 15 genome regions associated with drug resistance, including rpoB for rifampicin; katG and inhA promoter for isoniazid; gyrA and gyrB for ofloxacin and moxifloxacin; rpsL for streptomycin; rrs for streptomycin, amikacin, kanamycin and capreomycin; pncA and panD for pyrazinamide; embB, embC-embA, aftA , and ubiA for ethambutol; ethA for protionamide; and folC for para-aminosalicylic acid, were detected. Compared with traditional drug susceptibility testing results, the sensitivities for whole-genome sequencing of rifampin, isoniazid, ofloxacin, moxifloxacin, streptomycin, ethambutol, pyrazinamide, kanamycin, and amikacin resistance were 100%, 90.48%, 95.24%, 92.86%, 95.27%, 85.71%, 66.67%, 50%, and 50%, respectively. The sensitivities for whole-genome sequencing of capreomycin, protionamide, and para-aminosalicylic acid were not calculated because only one isolate showed phenotypic drug resistance. Mutations determined in drug susceptibility-associated genes can explain phenotypic drug resistance in most isolates. Notably, these mutations were absent in certain drug-resistant isolates, indicating other drug resistance mechanisms. Conclusion Whole-genome sequencing represents an effective diagnostic tool for fluoroquinolone-resistant and multidrug-resistant TB though it has some obstacles. Whole-genome sequencing should be used to predict drug resistance prior to performing traditional phenotypic drug susceptibility testing in Tianjin, China.

show abstract

Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

Characterization of Fluoroquinolone-Resistant and Multidrug-Resistant Mycobacterium tuberculosis Isolates Using Whole-Genome Sequencing in Tianjin, China

Wang¹,

Sun²,

Mu³

et al. 2022

IDR

View full text Add to dashboard Cite

show abstract

“…Mutations in embB 306, which is associated with the majority of drug-resistant strains to ethambutol, have also been detected in susceptible strains [ 31 ], whilst the same discrepancy for streptomycin might be due to low-level resistance-conferring mutations in gid to the drug, which may result in susceptible phenotype [ 33 ]. Mutations in rrs and rpsL genes have been associated with intermediate to high [ 34 ] and high levels of resistance to streptomycin [ 33 , 34 , 35 , 36 ], respectively. In addition, drug susceptibility testing is not routinely performed on all patients with TB, hence the treatment regimen in some cases may not be appropriate and this facilitates resistance amplification and further transmission of primary drug-resistant TB [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Whole-Genome Sequencing Reveals Recent Transmission of Multidrug-Resistant Mycobacterium tuberculosis CAS1-Kili Strains in Lusaka, Zambia

et al. 2021

Self Cite

View full text Add to dashboard Cite

Globally, tuberculosis (TB) is a major cause of death due to antimicrobial resistance. Mycobacterium tuberculosis CAS1-Kili strains that belong to lineage 3 (Central Asian Strain, CAS) were previously implicated in the spread of multidrug-resistant (MDR)-TB in Lusaka, Zambia. Thus, we investigated recent transmission of those strains by whole-genome sequencing (WGS) with Illumina MiSeq platform. Twelve MDR CAS1-Kili isolates clustered by traditional methods (MIRU-VNTR and spoligotyping) were used. A total of 92% (11/12) of isolates belonged to a cluster (≤12 SNPs) while 50% (6/12) were involved in recent transmission events, as they differed by ≤5 SNPs. All the isolates had KatG Ser315Thr (isoniazid resistance), EmbB Met306 substitutions (ethambutol resistance) and several kinds of rpoB mutations (rifampicin resistance). WGS also revealed compensatory mutations including a novel deletion in embA regulatory region (−35A > del). Several strains shared the same combinations of drug-resistance-associated mutations indicating transmission of MDR strains. Zambian strains belonged to the same clade as Tanzanian, Malawian and European strains, although most of those were pan-drug-susceptible. Hence, complimentary use of WGS to traditional epidemiological methods provides an in-depth insight on transmission and drug resistance patterns which can guide targeted control measures to stop the spread of MDR-TB.

show abstract

“…22,23,40 The following mutations confer resistance to STR, rpsL (Lys43Arg, Lys88Gln, Lys88Arg, Cys117Thr), rrs (Cys517Thr, Ala514Cys, Ala906Gly, Ala907Cys), gidB (Ala183Val, Gly71Arg, Tyr22His, Gly37Arg, Pro75Ser, Gly76Asp, Ile81Thr, Phe100Leu, Val124Gly, Ala134Gly, Ala138Pro, Ser149Arg, Leu152Ser, and Gly157Arg). 57 Mutations in the rpsL and rrs genes are the major mechanisms that confer resistance to STR in M. tuberculosis, they account for 60-70% of resistance to STR. 29 Recent studies have revealed that mutations in the gidB gene cause low-level resistance and accounts for 33% of resistance to STR in clinical M. tuberculosis isolates.…”

Section: Drug Target Genes and Mutations Conferring Resistance To Str...mentioning

confidence: 99%

Drug-target genes and their spontaneous mutations associated with resistance to first-line, second-line, third-line, novel and repurposed anti-tuberculosis drugs in Mycobacterium tuberculosis resistant strains

Mumena

Kwenda²,

Ngugi³

et al. 2022

IJMMTD

View full text Add to dashboard Cite

Drug-resistant tuberculosis is a threat to the control of tuberculosis globally, it develops mainly due to mutations in target genes of (MTB). Mutations in the rpoB gene confer resistance to rifampicin (RIF). The most frequent mutations conferring resistance to RIF include; Ser531Leu, Asp516Val, and His526Asp. Isoniazid resistance (INHr) occur most frequently due to mutations in the and its promoter. Most frequent mutation in is Ser315Thr 1, while in inhA include; Thr8Cys, Ala16Gly, and Cys15Thr. Mutations in , and genes confer resistance to ethambutol. 70% of mutations in the gene occur in codon 306, 406, or 497 and include; Met306Leu, Gly43Cys, and Ser412Pro. Mutations in the , and genes mediate resistance to pyrazinamide. Frequent mutations in A include; Tyr64Ser, Phe94Ala, and Trp68Gly. MTB resistance to streptomycin (STR) occur due to mutations in the , B, and L genes. Mutations (Ala80Pro), and L (Lys43Arg) confer resistance to STR. Fluoroquinolone resistance is mediated via mutations in the A and B genes. The most common mutations in the A gene include; Gly88Cys, Ala90Val, and Ser91Pro. While those in the gyrB gene include; Glu540Val, and Asn538Asp. Mutations in the rrs and promoter region cause resistance to the kanamycin and amikacin. While mutations in the and A cause resistance to capreomycin and viomycin. Common mutations in include; Cys1402Thr, Ala1401Gly, and Gly1484Thr. While mutations in the include; Cys12Thr, Gly10Ala, and Gly37Thr.Detection of drug-target genes and their mutations has therapeutic and diagnostic value.

show abstract

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

Cited by 14 publications

References 37 publications

Characterization of Fluoroquinolone-Resistant and Multidrug-Resistant Mycobacterium tuberculosis Isolates Using Whole-Genome Sequencing in Tianjin, China

Characterization of Fluoroquinolone-Resistant and Multidrug-Resistant Mycobacterium tuberculosis Isolates Using Whole-Genome Sequencing in Tianjin, China

Whole-Genome Sequencing Reveals Recent Transmission of Multidrug-Resistant Mycobacterium tuberculosis CAS1-Kili Strains in Lusaka, Zambia

Drug-target genes and their spontaneous mutations associated with resistance to first-line, second-line, third-line, novel and repurposed anti-tuberculosis drugs in Mycobacterium tuberculosis resistant strains

Contact Info

Product

Resources

About