Streptomycin Resistance and Lineage-Specific Polymorphisms in Mycobacterium tuberculosis gidB Gene

Streptomycin Resistance and Lineage-Specific Polymorphisms in Mycobacterium tuberculosis gidB Gene
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DOI:
10.1128/jcm.00168-11
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发表时间:
2011-07-01
影响因子:
9.4
通讯作者:
Zaha, Arnaldo
Zaha, Arnaldo
中科院分区:
医学2区
文献类型:
--
作者:
Spies, Fernanda S.;Ribeiro, Andrezza W.;Zaha, Arnaldo

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与rpsL和rrs基因中的链霉素抗性相关的突变是众所周知的,并且可以解释约70%的这种表型抗性。最近,gidB基因被发现与结核分枝杆菌的低水平链霉素耐药性有关。gidB突变已被报道的频率很高,这个基因似乎是非常多态性的,与移码和点突变发生在链霉素敏感和链霉素耐药菌株。在这项研究中,gidB突变出现在27%的链霉素耐药菌株中,这些菌株在rpsL或rrs基因中不含突变,并且它们与低水平的链霉素耐药性相关。然而,gidB的某些突变与链霉素耐药性的相关性需要进一步研究,因为我们也在链霉素敏感菌株中发现了gidB突变。这种情况仅发生在菌株对利福平和异烟肼耐药时。在本研究和其他链霉素敏感和耐药菌株的研究中,两种特定的突变非常频繁地出现;这些突变被认为与链霉素耐药无关,而是作为多态性。我们根据不同的系统发育谱系对菌株进行了分层,结果表明,gidB(16)多态性(16 G等位基因)仅存在于拉丁美洲-地中海(LAM)基因型中,而gidB(92)多态性(92 C等位基因)与另一人群中的北京谱系相关。在所研究的样本中,这两个特征性的单核苷酸多态性可以将LAM和北京血统与其他血统区分开来。
Mutations related to streptomycin resistance in the rpsL and rrs genes are well known and can explain about 70% of this phenotypic resistance. Recently, the gidB gene was found to be associated with low-level streptomycin resistance in Mycobacterium tuberculosis. Mutations in gidB have been reported with high frequency, and this gene appears to be very polymorphic, with frameshift and point mutations occurring in streptomycin-susceptible and streptomycin-resistant strains. In this study, mutations in gidB appeared in 27% of streptomycin-resistant strains that contained no mutations in the rpsL or rrs genes, and they were associated with low-level streptomycin resistance. However, the association of certain mutations in gidB with streptomycin resistance needs to be further investigated, as we also found mutations in gidB in streptomycin-susceptible strains. This occurred only when the strain was resistant to rifampin and isoniazid. Two specific mutations appeared very frequently in this and other studies of streptomycin-susceptible and -resistant strains; these mutations were not considered related to streptomycin resistance, but as a polymorphism. We stratified the strains according to the different phylogenetic lineages and showed that the gidB(16) polymorphism (16G allele) was exclusively present in the Latin American-Mediterranean (LAM) genotype, while the gidB(92) polymorphism (92C allele) was associated with the Beijing lineage in another population. In the sample studied, the two characterized single-nucleotide polymorphisms could distinguish LAM and Beijing lineages from the other lineages.