Genome-scale identification method applied to find cryptic aminoglycoside resistance genes in Pseudomonas aeruginosa.
Genome-scale identification method applied to find cryptic aminoglycoside resistance genes in Pseudomonas aeruginosa.
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DOI：
10.1371/journal.pone.0006576
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发表时间：
2009-11-11
期刊：
影响因子：
3.7
通讯作者：
Gill RT
中科院分区：
文献类型：
--
作者：
Struble JM;Gill RT
细菌迅速进化出对抗生素的耐药性的能力是一个关键的公共卫生问题。耐药性导致疾病严重程度和死亡率增加，并对发现和开发新的抗生素疗法施加压力。提高对抗性的进化和遗传基础的理解是微生物学领域的一个基本目标。我们已经应用了一种新的基因组方法，标量分析库富集（SCALEs），以确定基因组区域，增加拷贝数，可能会导致氨基糖苷类耐药铜绿假单胞菌在基因组规模。我们报告的结果高度代表性的基因组文库选择三种不同的氨基糖苷类抗生素（阿米卡星，庆大霉素，妥布霉素）。在基因组尺度上，我们发现每种评价的氨基糖苷类药物的基因存在显著（p<0.05）重叠。在鉴定的基因组片段中，我们证实了与几个基因组区域拷贝数增加相关的耐药性增加，包括最近与MexXY外排泵相关的氨基糖苷类耐药性PA 4943-PA 4946的PA 5471的ORF（编码可能的GTP结合蛋白、预测的宿主因子I蛋白、δ 2-异戊烯焦磷酸转移酶和DNA错配修复蛋白mutL），PA0960-PA0963（编码假定蛋白、可能的冷休克蛋白、可能的DNA结合应激蛋白和乙酰基-tRNA合成酶）、PA 4967的片段（编码拓扑异构酶IV亚基B）以及含有两个插入片段的嵌合克隆，所述插入片段包括ORF PA 0547和PA 2326（分别编码可能的转录调节因子和可能的假定蛋白）。本文报道的研究证明了新的基因组方法SCALEs的应用，该方法可用于提高对铜绿假单胞菌抗生素耐药性演变的理解。在我们的示范研究中，我们确定了大量的基因组区域，增加了对多种氨基糖苷类抗生素的耐药性。我们确定了包括开放阅读框的遗传区域，这些区域编码来自许多功能类别的产物，包括与O-抗原合成、DNA修复以及转录和翻译过程相关的基因。
The ability of bacteria to rapidly evolve resistance to antibiotics is a critical public health problem. Resistance leads to increased disease severity and death rates, as well as imposes pressure towards the discovery and development of new antibiotic therapies. Improving understanding of the evolution and genetic basis of resistance is a fundamental goal in the field of microbiology. We have applied a new genomic method, Scalar Analysis of Library Enrichments (SCALEs), to identify genomic regions that, given increased copy number, may lead to aminoglycoside resistance in Pseudomonas aeruginosa at the genome scale. We report the result of selections on highly representative genomic libraries for three different aminoglycoside antibiotics (amikacin, gentamicin, and tobramycin). At the genome-scale, we show significant (p<0.05) overlap in genes identified for each aminoglycoside evaluated. Among the genomic segments identified, we confirmed increased resistance associated with an increased copy number of several genomic regions, including the ORF of PA5471, recently implicated in MexXY efflux pump related aminoglycoside resistance, PA4943-PA4946 (encoding a probable GTP-binding protein, a predicted host factor I protein, a δ 2-isopentenylpyrophosphate transferase, and DNA mismatch repair protein mutL), PA0960–PA0963 (encoding hypothetical proteins, a probable cold shock protein, a probable DNA-binding stress protein, and aspartyl-tRNA synthetase), a segment of PA4967 (encoding a topoisomerase IV subunit B), as well as a chimeric clone containing two inserts including the ORFs PA0547 and PA2326 (encoding a probable transcriptional regulator and a probable hypothetical protein, respectively). The studies reported here demonstrate the application of new a genomic method, SCALEs, which can be used to improve understanding of the evolution of antibiotic resistance in P. aeruginosa. In our demonstration studies, we identified a significant number of genomic regions that increased resistance to multiple aminoglycosides. We identified genetic regions that include open reading frames that encode for products from many functional categories, including genes related to O-antigen synthesis, DNA repair, and transcriptional and translational processes.
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Pfam：氏族、网络工具和服务。
影响因子：
14.9
作者：
Finn, Robert D.;Mistry, Jaina;Schuster-Bockler, Benjamin;Griffiths-Jones, Sam;Hollich, Volker;Lassmann, Timo;Moxon, Simon;Marshall, Mhairi;Khanna, Ajay;Durbin, Richard;Eddy, Sean R.;Sonnhammer, Erik L. L.;Bateman, Alex
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DOI：
10.1016/j.ijantimicag.2004.11.012
发表时间：
2005-04-01
影响因子：
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作者：
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