Spread of a Chromosomal Cefixime-Resistant penA Gene among Different Neisseria gonorrhoeae Lineages

Spread of a Chromosomal Cefixime-Resistant penA Gene among Different Neisseria gonorrhoeae Lineages
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DOI:
10.1128/aac.01010-09
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发表时间:
2010-03-01
影响因子:
4.9
通讯作者:
Watanabe, Haruo
Watanabe, Haruo
中科院分区:
医学2区
文献类型:
--
作者:
Ohnishi, Makoto;Watanabe, Yuko;Watanabe, Haruo

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在淋病奈瑟菌中,编码青霉素结合蛋白2(PBP 2)的嵌合型佩纳与口服头孢菌素敏感性降低相关。探讨N.对32株淋球菌临床分离株的佩纳基因进行了测序。PBP 2有5种不同的氨基酸序列类型,但似乎都是PBP 2模式X的衍生物(PBP 2-X)。然而,多位点序列分型的分离物显示,分离物属于6个不同的序列类型。由于在三种不同的序列类型中鉴定了PBP 2-X,因此建议编码PBP 2-X的佩纳等位基因的水平转移。我们证明了佩纳基因可以通过自然转化从易感性降低的分离物转移到敏感分离物。将12个转化体的penA侧翼区的序列与供体和受体的序列进行比较,表明至少转移了包括佩纳基因的4-kb DNA片段。在水平转移过程中,由于等位基因内的点突变和遗传交换,一些佩纳等位基因也获得了变异。我们的研究结果提供了证据,自然转化的能力,在N。淋病在染色体抗生素抗性基因的传播和这些基因的多样性的产生中起作用。
In Neisseria gonorrhoeae, the mosaic type of penA, which encodes penicillin-binding protein 2 (PBP 2), is associated with reduced susceptibility to oral cephalosporins. To investigate the relatedness of N. gonorrhoeae clinical isolates with reduced susceptibility, we sequenced the penA genes of 32 isolates. Five different amino acid sequence types of PBP 2 were identified, but all seemed to be derivatives of pattern X of PBP 2 (PBP 2-X). However, multilocus sequence typing of the isolates showed that the isolates belonged to six different sequence types. As PBP 2-X was identified in three different sequence types, horizontal transfer of the penA allele encoding PBP2-X was suggested. We demonstrated that the penA gene could be transferred from an isolate with reduced susceptibility to a sensitive isolate by natural transformation. Comparison of the sequence of the penA-flanking regions of 12 transformants with those of the donor and the recipient suggested that at least a 4-kb DNA segment, including the penA gene, was transferred. During horizontal transfer, some of the penA alleles also acquired variations due to point mutations and genetic exchange within the allele. Our results provide evidence that the capacity for natural transformation in N. gonorrhoeae plays a role in the spread of chromosomal antibiotic resistance genes and the generation of diversity in such genes.