Genetic analysis of new 16S rRNA mutations conferring aminoglycoside resistance in Mycobacterium abscessus
Genetic analysis of new 16S rRNA mutations conferring aminoglycoside resistance in Mycobacterium abscessus
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DOI：
10.1093/jac/dkr209
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发表时间：
2011-08-01
影响因子：
5.2
通讯作者：
Gicquel, Brigitte
中科院分区：
文献类型：
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作者：
Nessar, Rachid;Reyrat, Jean Marc;Gicquel, Brigitte
目的：我们研究的发展和健身成本的2-脱氧链霉胺氨基糖苷类耐药的Mycobacteriumsessus.Methods：自发的2-脱氧链霉胺氨基糖苷类耐药突变株进行了选择，并确定其出现的频率。对rrs基因的3'部分进行测序以表征突变。此外，我们还测定了氨基糖苷类药物对不同突变体的MIC。显性/隐性性状的不同的突变进行了检查，我们探讨了潜在的成本所赋予的突变在体外选择的健身这些菌株与野生型strain.Results：2-脱氧链霉胺氨基糖苷类耐药的体外突变率是相似的10（-7）突变/细胞分裂。除了在1408位（大肠杆菌编号）的已知rrs A -> G取代（其赋予卡那霉素抗性（Kan（R））之外，在M中鉴定了rrs中的三个新取代。突变体，即1406处的T -> A，1409处的C -> T和1491处的G -> T。携带基因组突变T -> A在1406和A -> G在1408与野生型rrs基因由pNBV 1载体携带的异源二倍体显示抗性表型。相反，携带基因组突变C -> T在1409和G -> T在1491与野生型rrs基因携带的pNBV 1载体具有易感表型。结论：rrs基因突变可使耐2-脱氧链霉胺氨基糖苷类抗生素的支原体产生高水平耐药性。在我们的实验条件下，它们的显性/隐性性状不同，没有生物学成本。
Objectives: We studied the development and fitness cost of 2-deoxystreptamine aminoglycoside resistance of Mycobacterium abscessus.Methods: Spontaneous 2-deoxystreptamine aminoglycoside-resistant mutants were selected and the frequency of their appearance was determined. The 3' part of the rrs gene was sequenced to characterize mutations. Additionally, we determined the MICs of aminoglycoside drugs for the different mutants obtained. The dominance/recessivity traits of the different mutations were examined and we explored the potential cost conferred by the mutations selected in vitro on the fitness of these isolates compared with the wild-type strain.Results: The in vitro mutation rate for 2-deoxystreptamine aminoglycoside resistance was similar to 10(-7) mutations/cell division. In addition to the known rrs A -> G substitution at position 1408 (Escherichia coli numbering), which confers kanamycin resistance (Kan(R)), three new substitutions in rrs were identified in M. abscessus Kan(R) mutants, i.e. T -> A at 1406, C -> T at 1409 and G -> T at 1491. Heterodiploids carrying genomic mutations T -> A at 1406 and A -> G at 1408 with the wild-type rrs gene carried by the pNBV1 vector showed a resistant phenotype. In contrast, heterodiploids carrying genomic mutations C -> T at 1409 and G -> T at 1491 with the wild-type rrs gene carried by the pNBV1 vector had a susceptible phenotype. No burden on fitness was observed for the different mutations.Conclusion: Mutations in the rrs gene that confer high-level 2-deoxystreptamine aminoglycoside resistance on M. abscessus differ in their dominance/recessivity traits and have no biological cost under our experimental conditions.