Evaluation of gidB alterations responsible for streptomycin resistance in Mycobacterium tuberculosis

Verma, J.; Gupta, Yash; Nair, Deepthi; Manzoor, Nikhat; Rautela, Rajinder S.; Rai, Arvind; Katoch, Vishwa Mohan

doi:10.1093/jac/dku273

Cited by 30 publications

(25 citation statements)

References 24 publications

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“…The occurrence of gid B mutations in strains reduces drug pressure for selection of highly resistant isolates, therefore it has been suggested that high-level streptomycin resistant strains (e.g. rps L mutants) arise more frequently in gid B mutants than in wild-type cells [61]. We observed six streptomycin resistant strains without mutations in rps L, rrs or gid B.…”

Section: Discussionmentioning

confidence: 78%

Whole Genome Sequencing Based Characterization of Extensively Drug-Resistant Mycobacterium tuberculosis Isolates from Pakistan

et al. 2015

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Improved molecular diagnostic methods for detection drug resistance in Mycobacterium tuberculosis (MTB) strains are required. Resistance to first- and second- line anti-tuberculous drugs has been associated with single nucleotide polymorphisms (SNPs) in particular genes. However, these SNPs can vary between MTB lineages therefore local data is required to describe different strain populations. We used whole genome sequencing (WGS) to characterize 37 extensively drug-resistant (XDR) MTB isolates from Pakistan and investigated 40 genes associated with drug resistance. Rifampicin resistance was attributable to SNPs in the rpoB hot-spot region. Isoniazid resistance was most commonly associated with the katG codon 315 (92%) mutation followed by inhA S94A (8%) however, one strain did not have SNPs in katG, inhA or oxyR-ahpC. All strains were pyrazimamide resistant but only 43% had pncA SNPs. Ethambutol resistant strains predominantly had embB codon 306 (62%) mutations, but additional SNPs at embB codons 406, 378 and 328 were also present. Fluoroquinolone resistance was associated with gyrA 91–94 codons in 81% of strains; four strains had only gyrB mutations, while others did not have SNPs in either gyrA or gyrB. Streptomycin resistant strains had mutations in ribosomal RNA genes; rpsL codon 43 (42%); rrs 500 region (16%), and gidB (34%) while six strains did not have mutations in any of these genes. Amikacin/kanamycin/capreomycin resistance was associated with SNPs in rrs at nt1401 (78%) and nt1484 (3%), except in seven (19%) strains. We estimate that if only the common hot-spot region targets of current commercial assays were used, the concordance between phenotypic and genotypic testing for these XDR strains would vary between rifampicin (100%), isoniazid (92%), flouroquinolones (81%), aminoglycoside (78%) and ethambutol (62%); while pncA sequencing would provide genotypic resistance in less than half the isolates. This work highlights the importance of expanded targets for drug resistance detection in MTB isolates.

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Section: Discussionmentioning

confidence: 78%

Whole Genome Sequencing Based Characterization of Extensively Drug-Resistant Mycobacterium tuberculosis Isolates from Pakistan

et al. 2015

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“…In each case, the frameshift occurs within the region encoding the GidB methyltransferase domain. Mutations in gidB (rsmG) are associated with low-level streptomycin resistance in several species of bacteria including S. aureus [33][34][35][36] and it is speculated that loss of 16S methylation lowers the binding affinity of streptomycin thus conferring the resistance phenotype 35 . Here, a gidB transposon mutant was found to be 4-fold less susceptible to steptomycin ( Table 1, Table S3).…”

Section: Resultsmentioning

confidence: 99%

Genomic signatures of experimental adaptation to antimicrobial peptides inStaphylococcus aureus

Johnston

Dobson

Rolff

2015

Preprint

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ObjectivesThe evolution of resistance against antimicrobial peptides has long been considered unlikely due to their mechanism of action, yet experimental selection with AMPs results in rapid evolution of resistance in several species of bacteria. Although numerous studies have utilized mutant screens to identify loci that determine AMP susceptibility, there is a dearth of data concerning the genomic changes which accompany experimental evolution of AMP resistance.MethodsUsing genome re-sequencing we analysed the mutations which arise during experimental evolution of resistance to the cationic AMPs iseganan, melittin and pexiganan, as well as to a combination of melittin and pexiganan, or to the aminoglycoside antibiotic streptomycin.ResultsAnalysis of 17 independently replicated Staphylococcus aureus selection lines, including unselected controls, showed that each AMP selected for mutations at distinct loci. We identify mutations in genes involved in the synthesis and maintenance of the cell envelope. This includes genes previously identified from mutant screens for AMP resistance, and genes involved in the response to AMPs and cell-wall-active antibiotics. Furthermore, transposon insertion mutants were used to verify that a number of the identified genes are directly involved in determining AMP susceptibility.ConclusionsStrains selected for AMP resistance under controlled experimental evolution displayed consistent AMP-specific mutations in genes which determine AMP susceptibility. This suggests that different routes to evolve resistance are favored within a controlled genetic background.

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“…The study by Spies et al showed gidB mutations in 49% of the streptomycin resistant clinical isolates studied and suggests efflux pump inhibitors could act in synergy with mutations in gidB to confer low-level streptomycin resistance in M. tuberculosis [86]. Other studies showed a similar percentage of gidB mutations associated with streptomycin resistant M. tuberculosis clinical isolates [55,56]. Also, the percentage of gidB mutations associated with streptomycin resistant M. tuberculosis clinical isolates from different regions of the world were seen in 34%, 3%, and 38% of streptomycin resistant M. tuberculosis clinical isolates in Pakistan, Cameroon, and Poland, respectively [82e84].…”

Section: Antibiotic Resistancementioning

confidence: 95%

RNA modification enzymes encoded by the gid operon: Implications in biology and virulence of bacteria

Shippy

Fadl

2015

Microbial Pathogenesis

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Evaluation of gidB alterations responsible for streptomycin resistance in Mycobacterium tuberculosis

Cited by 30 publications

References 24 publications

Whole Genome Sequencing Based Characterization of Extensively Drug-Resistant Mycobacterium tuberculosis Isolates from Pakistan

Whole Genome Sequencing Based Characterization of Extensively Drug-Resistant Mycobacterium tuberculosis Isolates from Pakistan

Genomic signatures of experimental adaptation to antimicrobial peptides inStaphylococcus aureus

RNA modification enzymes encoded by the gid operon: Implications in biology and virulence of bacteria

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