Genetic Organization of Transposase Regions Surrounding blaKPC Carbapenemase Genes on Plasmids from Klebsiella Strains Isolated in a New York City Hospital
Genetic Organization of Transposase Regions Surrounding blaKPC Carbapenemase Genes on Plasmids from Klebsiella Strains Isolated in a New York City Hospital
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DOI：
10.1128/aac.01355-08
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发表时间：
2009-05-01
影响因子：
4.9
通讯作者：
Huard, Richard C.
中科院分区：
文献类型：
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作者：
Gootz, Thomas D.;Lescoe, Mary Kay;Huard, Richard C.
携带肺炎克雷伯菌碳青霉烯酶（KPC）的碳青霉烯类耐药克雷伯菌属菌株是纽约市的地方病，并正在美国和国际上传播。最近的研究表明，KPC结构基因位于一个10 kb的质粒携带元件命名为Tn 4401。对2005年在纽约市医院分离的14株携带bla（KPC-2）或bla（KPC-3）的肺炎克雷伯菌和1株产酸克雷伯菌进行Tn 4401亚型检查。10个克雷伯氏菌菌株在Tn 4401中含有100-bp缺失，对应于Tn 4401 a同种型。在Tn 4401 a中邻近bla（KPC）上游启动子区的这种缺失的存在导致TGGAGA的-35启动子序列不同于存在于同种型Tn 4401 b中的CTGATT的-35启动子序列。一个质粒携带bla（KPC）从三个非克隆分离株的完整测序表明存在编码其他类型的抗生素耐药决定簇的基因。从K.携带bla（KPC-2）的肺炎链球菌S9显示了以反向方式插入的Tn 4401 b的两个相同拷贝，但在这种情况下，其中一个元件破坏了II组自剪接内含子。在K. pneumoniae菌株S15中，携带bla（KPC-2）的Tn 4401 a元件存在于大的120-kb质粒和较小的24-kb质粒上。脉冲场凝胶电泳结果表明，研究的菌株代表了一个异质组，由无关以及密切相关的克雷伯氏菌菌株。我们的研究结果表明，地方性KPC阳性克雷伯菌菌株构成了一个一般的非克隆人口的bla（KPC）的几个不同的质粒遗传背景的各种等位基因。这项研究增加了我们对KPC生产，医疗保健相关，革兰氏阴性病原体的进化和扩展作用的遗传组成的理解。
Carbapenem-resistant Klebsiella strains carrying Klebsiella pneumoniae carbapenemases (KPC) are endemic to New York City and are spreading across the United States and internationally. Recent studies have indicated that the KPC structural gene is located on a 10-kb plasmid-borne element designated Tn4401. Fourteen Klebsiella pneumoniae strains and one Klebsiella oxytoca strain isolated at a New York City hospital in 2005 carrying either bla(KPC-2) or bla(KPC-3) were examined for isoforms of Tn4401. Ten of the Klebsiella strains contained a 100-bp deletion in Tn4401, corresponding to the Tn4401a isoform. The presence of this deletion adjacent to the upstream promoter region of bla(KPC) in Tn4401a resulted in a different -35 promoter sequence of TGGAGA than that of CTGATT present in isoform Tn4401b. Complete sequencing of one plasmid carrying bla(KPC) from each of three nonclonal isolates indicated the presence of genes encoding other types of antibiotic resistance determinants. The 70.6-kb plasmid from K. pneumoniae strain S9 carrying bla(KPC-2) revealed two identical copies of Tn4401b inserted in an inverse fashion, but in this case, one of the elements disrupted a group II self-splicing intron. In K. pneumoniae strain S15, the Tn4401a element carrying bla(KPC-2) was found on both a large 120-kb plasmid and a smaller 24-kb plasmid. Pulsed-field gel electrophoresis results indicate that the isolates studied represent a heterogeneous group composed of unrelated as well as closely related Klebsiella strains. Our results suggest that endemic KPC-positive Klebsiella strains constitute a generally nonclonal population comprised of various alleles of bla(KPC) on several distinct plasmid genetic backgrounds. This study increases our understanding of the genetic composition of the evolving and expanding role of KPC-producing, healthcare-associated, gram-negative pathogens.