Genomic analysis of the emergence and evolution of multidrug resistance during a Klebsiella pneumoniae outbreak including carbapenem and colistin resistance
Genomic analysis of the emergence and evolution of multidrug resistance during a Klebsiella pneumoniae outbreak including carbapenem and colistin resistance
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DOI：
10.1093/jac/dkt419
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发表时间：
2014-03-01
影响因子：
5.2
通讯作者：
Mingorance, Jesus
中科院分区：
文献类型：
--
作者：
Lopez-Camacho, Elena;Gomez-Gil, Rosa;Mingorance, Jesus
目的：在基因组水平上描述烧伤重症监护病房肺炎克雷伯菌暴发期间多重耐药的演变。爆发涉及DHA-1 β-内酰胺酶生产菌株，后来获得碳青霉烯和磷霉素耐药，并在一个案例中粘菌素resistance.Methods：两个菌株的基因组测序和比较与先前测序的基因组。超变的作用进行了研究，通过测量的突变频率的菌株和比较与一组对照strain.Results：序列比较确定了四个单核苷酸变异体和两个转座子插入。对整个收集物中的变异体进行分析，这些变异体与碳青霉烯类和磷霉素对ompK 36孔蛋白基因中的无义突变的耐药性以及粘菌素对mgrB基因中IS 1插入的耐药性有关。携带bla（DHA-1）基因的质粒在没有抗生素的情况下是不稳定的，对丢失质粒的分离株的分析表明，单独的孔蛋白突变不足以产生碳青霉烯耐药性。所有菌株的突变频率相似analysed.Conclusions：碳青霉烯耐药需要生产的DHA-1 β-内酰胺酶和降低渗透性，但磷霉素耐药只依赖于渗透性。对粘菌素的耐药性可能与phoPQ系统调节的改变有关。超突变与孔蛋白突变体的选择无关。质粒的不稳定性可能是由于大量的移动的元件，并表明抗生素选择压力在这次疫情的出现和演变中发挥了重要作用。
Objectives: To characterize at the genomic level the evolution of multiresistance during an outbreak of Klebsiella pneumoniae in a burns intensive care unit. The outbreak involved a DHA-1 beta-lactamase-producing strain that later acquired carbapenem and fosfomycin resistance, and in one case colistin resistance.Methods: The genomes of two isolates were sequenced and compared with a previously sequenced genome. The role of hypermutability was investigated by measuring the mutation frequencies of the isolates and comparison with a collection of control strains.Results: Sequence comparison identified four single-nucleotide variants and two transposon insertions. Analysis of the variants in the whole collection related carbapenem and fosfomycin resistance to a nonsense mutation in the ompK36 porin gene and colistin resistance to an IS1 insertion in the mgrB gene. The plasmid carrying the bla(DHA-1) gene was unstable in the absence of antibiotics, and analysis of isolates that had lost the plasmid showed that the porin mutation alone was not sufficient to generate carbapenem resistance. The mutation frequencies were similar among all the strains analysed.Conclusions: Carbapenem resistance required production of the DHA-1 beta-lactamase and decreased permeability, but fosfomycin resistance depended only on permeability. Resistance to colistin might be related to an alteration in the regulation of the phoPQ system. Hypermutation is not related to the selection of porin mutants. Plasmid instability might be due to the high number of mobile elements and suggests a major role for antibiotic selection pressure in the emergence and evolution of this outbreak.