Genomewide Identification of Genetic Determinants of Antimicrobial Drug Resistance in Pseudomonas aeruginosa
Genomewide Identification of Genetic Determinants of Antimicrobial Drug Resistance in Pseudomonas aeruginosa
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DOI：
10.1128/aac.00035-09
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发表时间：
2009-06-01
影响因子：
4.9
通讯作者：
Haeussler, Susanne
中科院分区：
文献类型：
--
作者：
Doetsch, Andreas;Becker, Tanja;Haeussler, Susanne
由于感染延迟治疗的风险增加、住院时间延长、护理成本大幅增加以及致命结局的高风险，抗菌药物耐药性的出现引起了公众的极大关注。开发有效的治疗替代方案的先决条件是详细了解耐药性背后的细菌机制的多样性，特别是对于有问题的革兰氏阴性细菌，如铜绿假单胞菌。这种病原体具有令人印象深刻的染色体编码的内在抗性机制，以及突变的潜力，从而获得对当前抗生素的抗性。在这项研究中，我们筛选了全面的非冗余哈佛PA 14库的铜绿假单胞菌突变体，表现出增加或减少对19种抗生素的耐药性在临床上常用。这种方法确定了几个基因，这些基因的失活使细菌对广谱不同的抗菌剂敏感，并发现了对各种抗生素耐药性的新遗传决定因素。增强细菌对现有抗生素的敏感性和新的耐药标志物或耐药表达修饰剂的知识可能为有效的治疗方案奠定基础，并将成为开发控制多重耐药革兰氏阴性菌的新策略的基础。
The emergence of antimicrobial drug resistance is of enormous public concern due to the increased risk of delayed treatment of infections, the increased length of hospital stays, the substantial increase in the cost of care, and the high risk of fatal outcomes. A prerequisite for the development of effective therapy alternatives is a detailed understanding of the diversity of bacterial mechanisms that underlie drug resistance, especially for problematic gram-negative bacteria such as Pseudomonas aeruginosa. This pathogen has impressive chromosomally encoded mechanisms of intrinsic resistance, as well as the potential to mutate, gaining resistance to current antibiotics. In this study we have screened the comprehensive nonredundant Harvard PA14 library for P. aeruginosa mutants that exhibited either increased or decreased resistance against 19 antibiotics commonly used in the clinic. This approach identified several genes whose inactivation sensitized the bacteria to a broad spectrum of different antimicrobials and uncovered novel genetic determinants of resistance to various classes of antibiotics. Knowledge of the enhancement of bacterial susceptibility to existing antibiotics and of novel resistance markers or modifiers of resistance expression may lay the foundation for effective therapy alternatives and will be the basis for the development of new strategies in the control of problematic multiresistant gram-negative bacteria.