Transcriptome Profiling of Antimicrobial Resistance in Pseudomonas aeruginosa
Transcriptome Profiling of Antimicrobial Resistance in Pseudomonas aeruginosa
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DOI：
10.1128/aac.00075-16
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发表时间：
2016-08-01
影响因子：
4.9
通讯作者：
Haeussler, Susanne
中科院分区：
文献类型：
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作者：
Khaledi, Ariane;Schniederjans, Monika;Haeussler, Susanne
新出现的抗微生物药物耐药性和缺乏新的抗生素候选药物强调了优化当前诊断和治疗的必要性，以减少多药耐药性的演变和传播。由于细菌病原体的抗生素耐药性状态是由其基因组定义的，因此通过应用下一代测序（NGS）技术进行的耐药性分析可能在未来实现病原体鉴定，促进启动有针对性的个体化治疗，并实施优化的感染控制措施。在这项研究中，定性RNA测序被用来确定135个临床铜绿假单胞菌分离株的抗生素耐药性的关键遗传决定因素，从不同的地理和感染部位的起源。通过应用全转录组关联研究，鉴定了与对抗生素类氟喹诺酮类、氨基糖苷类和β-内酰胺类的耐药性相关的适应性变异。除了与抗性直接相关的潜在新型生物标志物外，还通过预测机器学习方法鉴定了表型相关基因表达和序列变异的全局模式。我们的研究有助于建立基于基因型的分子诊断工具，用于识别细菌病原体的当前耐药性，并为更快的诊断铺平道路，以实现更有效，更有针对性的治疗策略，从而减轻未来耐药性演变的可能性。
Emerging resistance to antimicrobials and the lack of new antibiotic drug candidates underscore the need for optimization of current diagnostics and therapies to diminish the evolution and spread of multidrug resistance. As the antibiotic resistance status of a bacterial pathogen is defined by its genome, resistance profiling by applying next-generation sequencing (NGS) technologies may in the future accomplish pathogen identification, prompt initiation of targeted individualized treatment, and the implementation of optimized infection control measures. In this study, qualitative RNA sequencing was used to identify key genetic determinants of antibiotic resistance in 135 clinical Pseudomonas aeruginosa isolates from diverse geographic and infection site origins. By applying transcriptome-wide association studies, adaptive variations associated with resistance to the antibiotic classes fluoroquinolones, aminoglycosides, and beta-lactams were identified. Besides potential novel biomarkers with a direct correlation to resistance, global patterns of phenotype-associated gene expression and sequence variations were identified by predictive machine learning approaches. Our research serves to establish genotype-based molecular diagnostic tools for the identification of the current resistance profiles of bacterial pathogens and paves the way for faster diagnostics for more efficient, targeted treatment strategies to also mitigate the future potential for resistance evolution.