Complete Sequence of a Novel 178-Kilobase Plasmid Carrying blaNDM-1 in a Providencia stuartii Strain Isolated in Afghanistan
Complete Sequence of a Novel 178-Kilobase Plasmid Carrying blaNDM-1 in a Providencia stuartii Strain Isolated in Afghanistan
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DOI：
10.1128/aac.05604-11
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发表时间：
2012-04-01
影响因子：
4.9
通讯作者：
Waterman, Paige E.
中科院分区：
文献类型：
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作者：
Mc Gann, Patrick;Hang, Jun;Waterman, Paige E.
为了回应全球对新德里金属-β-内酰胺酶基因 1 (bla(NDM-1)) 传播的担忧，我们于 2010 年 9 月启动了每月监测计划。所有转送到我们工厂的碳青霉烯类耐药革兰氏阴性菌株均经过该基因筛查。迄今为止，已测试了 321 种耐碳青霉烯类菌株，涵盖 11 种细菌。 2011年2月，从阿富汗一家军事医院提交的两株斯氏普罗维登斯菌，检测结果呈bla(NDM-1)阳性。脉冲场凝胶电泳（PFGE）显示这两种菌株是相同的。 bla(NDM-1) 携带在大质粒 pMR0211 上，通过乳液 PCR 和焦磷酸测序对其进行测序。 pMR0211 大小为 178,277 bp，属于不相容组 A/C。该质粒由与大肠杆菌的 pAR060302 具有相当大同源性的主链组成，并且保留了许多与其相关的抗生素抗性基因。该质粒还与 pNDM-HK 质粒共享相同的元件，包括 bla(NDM-1)、armA 和 sull。然而，基因方向相反，pMR0211 中不存在该区域的 3 kb 片段。 pMR0211 还包含其他基因，包括氨基糖苷修饰酶位点 aadA 和 aac(6')、喹诺酮抗性基因 qnrA（与亚马逊希瓦氏菌 U32 家族肽酶同源性最高的基因）以及 bla(OXA-10) 基因。在本质上对粘菌素具有抗性的物种（例如普罗维登斯氏菌）中发现该基因尤其令人担忧，因为它使该生物体对几乎所有可用的抗生素都具有抗药性。含有 bla(NDM-1) 基因的区域侧翼存在多个插入序列和转座子，进一步凸显了与该基因相关的潜在移动性。
In response to global concerns over the spread of the New Delhi metallo-beta-lactamase gene 1, bla(NDM-1), a monthly surveillance program was initiated in September 2010. All carbapenem-resistant Gram-negative strains forwarded to our facility are screened for this gene. To date, 321 carbapenem-resistant isolates, encompassing 11 bacterial species, have been tested. In February 2011, two strains of Providencia stuartii, submitted from a military hospital in Afghanistan, tested positive for bla(NDM-1). Both strains were identical by pulsed-field gel electrophoresis (PFGE). bla(NDM-1) was carried on a large plasmid, pMR0211, which was sequenced by emulsion PCR and pyrosequencing. pMR0211 is 178,277 bp in size and belongs to incompatibility group A/C. The plasmid consists of a backbone with considerable homology to pAR060302 from Escherichia coli, and it retains many of the antibiotic resistance genes associated with it. The plasmid also shares common elements with the pNDM-HK plasmid, including bla(NDM-1), armA, and sull. However, gene orientation is reversed, and a 3-kb fragment from this region is absent from pMR0211. pMR0211 also contains additional genes, including the aminoglycoside-modifying enzyme loci aadA and aac(6'), the quinolone resistance gene qnrA, a gene with highest homology to a U32 family peptidase from Shewanella amazonensis, and the bla(OXA-10) gene. The finding of this gene in an intrinsically colistin-resistant species such as Providencia stuartii is especially worrisome, as it renders the organism resistant to nearly every available antibiotic. The presence of multiple insertion sequences and transposons flanking the region containing the bla(NDM-1) gene further highlights the potential mobility associated with this gene.