Comparison of clinical isolates and in vitro selected mutants reveals that tlyA is not a sensitive genetic marker for capreomycin resistance in Mycobacterium tuberculosis

Engström, Arne; Perskvist, Nasrin; Werngren, Jim; Hoffner, Sven; Juréen, Pontus

doi:10.1093/jac/dkr109

Cited by 59 publications

(56 citation statements)

References 21 publications

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“…The eis Ϫ10G¡A and Ϫ12C¡T SNPs had almost 100% specificity for KAN r (Table 7) but were not specific for AMK r or CAP r , as they occurred more often in AMK s and CAP s isolates than in AMK r and CAP r isolates. Similar to previous studies (23), SNPs observed in the tlyA gene in isolates resistant to AMK, KAN, and/or CAP were not found to be sensitive or specific for phenotypic resistance in this analysis (see Tables S1 to S4 in the supplemental material).…”

Section: Dstsupporting

confidence: 86%

Predicting Extensively Drug-Resistant Mycobacterium tuberculosis Phenotypes with Genetic Mutations

et al. 2014

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Section: Dstsupporting

confidence: 86%

Predicting Extensively Drug-Resistant Mycobacterium tuberculosis Phenotypes with Genetic Mutations

et al. 2014

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“…AMK, KAN, and CAP are key drugs for treating MDR TB, and the most common mutations associated with a resistance of these drugs are located within the rrs gene coding for 16S rRNA (4,19,20). We therefore analyzed a 481-bp region of this gene.…”

Section: Resultsmentioning

confidence: 99%

“…In the present study, one pre-XDR isolate resistant to KAN, AMK, and CAP was also found to contain the C1402T mutation in rrs (Table 3), but the A1401G and G1484T mutations associated with AMK resistance in the rrs gene were not detected. Since the C1402T mutation has not been shown to confer resistance to AMK (19), this suggests at least another unknown mechanism for AMK resistance in the isolate. Similar to other studies (9,21), no mutation was detected in the rrs gene in four resistant strains.…”

Section: Discussionmentioning

confidence: 99%

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Molecular Characterization of Multidrug- and Extensively Drug-Resistant Mycobacterium tuberculosis Strains in Jiangxi, China

et al. 2012

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In this study, a total of 77 multidrug-resistant and extensively drug-resistant (MDR and XDR, respectively) isolates of Mycobacterium tuberculosis were characterized among samples from patients living in Jiangxi province, China. The following two approaches were used: (i) genotyping all drug-resistant isolates by the 15-locus MIRU-VNTR (mycobacterial interspersed repetitive-unit-variable-number tandem-repeat) method and identifying the Beijing family genotype using the RD105 deletion targeted multiplex PCR and (ii) determining the mutation profiles associated with the resistance to the first-line antituberculous drugs rifampin (RIF) and isoniazid (INH) and the second-line drugs ofloxacin (OFX), kanamycin (KAN), amikacin (AMK), and capreomycin (CAP) with DNA sequencing. Six loci were examined: rpoB (for resistance to RIF), katG and mabA-inhA (INH), gyrA and gyrB (OFX), and rrs (KAN, AMK, and CAP). It is shown that the Beijing genotype was predominant (80.5%) among these strains and that the selected drug-resistant strains were genetically diverse, suggesting that they probably had independently acquired drug resistance. In comparison to the phenotypic data, the sensitivities for the detection of RIF, INH, OFX, and KAN/AMK/CAP resistance by DNA sequencing were 94.8, 80.5, 84.6, and 78.9%, respectively. The most prevalent mutations involved in RIF, INH, OFX, and KAN/AMK/CAP resistance were Ser531Leu in rpoB (44.2%), Ser315Thr in katG (55.8%) and C-15T in mabA-inhA (11.7%), Asp94Gly in gyrA (48.7%), and A1401G in rrs (73.7%), respectively. Five novel katG mutants (Trp191Stop, Thr271Pro, Trp328Phe, Leu546Pro, and Asp695Gly) and six new alleles (Ile569Val, Ile572Met, Phe584Ser, Val615Met, Asp626Glu, and Lys972Thr) in the rpoB gene were identified.

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“…Amikacin (AMK), kanamycin (KAN), and capreomycin (CAP) inhibit protein synthesis by binding to the ribosome (21,31,38). Resistance to all three drugs is associated with mutations in the 16S rRNA gene rrs, specifically at nucleotide positions 1401, 1402, and 1484 (1,11,28,54,57). A mutation at nucleotide 1401 or 1484 is associated with resistance to all these agents, whereas a mutation at nucleotide 1402 is associated with CAP resistance and low-level KAN resistance (11,28).…”

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confidence: 99%

Detection of First- and Second-Line Drug Resistance in Mycobacterium tuberculosis Clinical Isolates by Pyrosequencing

Engström

Morcillo²,

Imperiale³

et al. 2012

J Clin Microbiol

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Conventional phenotypic drug susceptibility testing (DST) methods for Mycobacterium tuberculosis are laborious and very time-consuming. Early detection of drug-resistant tuberculosis (TB) is essential for prevention and control of TB transmission. We have developed a pyrosequencing method for simultaneous detection of mutations associated with resistance to rifampin, isoniazid, ethambutol, amikacin, kanamycin, capreomycin, and ofloxacin. Seven pyrosequencing assays were optimized for following loci: rpoB , katG , embB , rrs , gyrA , and the promoter regions of inhA and eis . The molecular method was evaluated on a panel of 290 clinical isolates of M. tuberculosis . In comparison to phenotypic DST, the pyrosequencing method demonstrated high specificity (100%) and sensitivity (94.6%) for detection of multidrug-resistant M. tuberculosis as well as high specificity (99.3%) and sensitivity (86.9%) for detection of extensively drug-resistant M. tuberculosis . The short turnaround time combined with multilocus sequencing of several isolates in parallel makes pyrosequencing an attractive method for drug resistance screening in M. tuberculosis .

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Comparison of clinical isolates and in vitro selected mutants reveals that tlyA is not a sensitive genetic marker for capreomycin resistance in Mycobacterium tuberculosis

Cited by 59 publications

References 21 publications

Predicting Extensively Drug-Resistant Mycobacterium tuberculosis Phenotypes with Genetic Mutations

Predicting Extensively Drug-Resistant Mycobacterium tuberculosis Phenotypes with Genetic Mutations

Molecular Characterization of Multidrug- and Extensively Drug-Resistant Mycobacterium tuberculosis Strains in Jiangxi, China

Detection of First- and Second-Line Drug Resistance in Mycobacterium tuberculosis Clinical Isolates by Pyrosequencing

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