López-Causapé Carla, Cabot Gabriel, Del Barrio-Tofiño Ester, Oliver Antonio
Servicio de Microbiología y Unidad de Investigación, Hospital Universitari Son Espases, Institut d'Investigació Sanitaria Illes Balears, Palma de Mallorca, Spain.
Front Microbiol. 2018 Apr 6;9:685. doi: 10.3389/fmicb.2018.00685. eCollection 2018.
One of the most striking features of is its outstanding capacity for developing antimicrobial resistance to nearly all available antipseudomonal agents through the selection of chromosomal mutations, leading to the failure of the treatment of severe hospital-acquired or chronic infections. Recent whole-genome sequencing (WGS) data obtained from assays on the evolution of antibiotic resistance, monitoring of antimicrobial resistance development, analysis of sequential cystic fibrosis isolates, and characterization of widespread epidemic high-risk clones have provided new insights into the evolutionary dynamics and mechanisms of antibiotic resistance, thus motivating this review. Indeed, the analysis of the WGS mutational resistome has proven to be useful for understanding the evolutionary dynamics of classical resistance pathways and to describe new mechanisms for the majority of antipseudomonal classes, including β-lactams, aminoglycosides, fluoroquinolones, or polymixins. Beyond addressing a relevant scientific question, the analysis of the mutational resistome is expected to be useful, together with the analysis of the horizontally-acquired resistance determinants, for establishing the antibiotic resistance genotype, which should correlate with the antibiotic resistance phenotype and as such, it should be useful for the design of therapeutic strategies and for monitoring the efficacy of administered antibiotic treatments. However, further experimental research and new bioinformatics tools are still needed to overcome the interpretation limitations imposed by the complex interactions (including those leading to collateral resistance or susceptibility) between the 100s of genes involved in the mutational resistome, as well as the frequent difficulties for differentiating relevant mutations from simple natural polymorphisms.
（文本中“One of the most striking features of is...”部分缺失关键信息，无法准确翻译完整句子。以下是根据现有内容翻译的部分）通过选择染色体突变，对几乎所有可用的抗假单胞菌药物产生抗菌耐药性的能力是其最显著的特征之一，这导致严重医院获得性感染或慢性感染的治疗失败。最近从抗生素耐药性进化分析、抗菌耐药性发展监测、连续性囊性纤维化分离株分析以及广泛流行的高风险克隆特征分析的检测中获得的全基因组测序（WGS）数据，为[具体细菌名称]抗生素耐药性的进化动态和机制提供了新见解，从而促成了本综述。确实，对WGS突变耐药组的分析已被证明有助于理解经典耐药途径的进化动态，并描述大多数抗假单胞菌类药物（包括β-内酰胺类、氨基糖苷类、氟喹诺酮类或多粘菌素类）的新机制。除了解决一个相关的科学问题外，对[具体细菌名称]突变耐药组的分析预计将与水平获得的耐药决定因素分析一起，用于确定抗生素耐药基因型，该基因型应与抗生素耐药表型相关，因此，它应有助于治疗策略的设计和监测所给予抗生素治疗的疗效。然而，仍需要进一步的实验研究和新的生物信息学工具来克服由突变耐药组中涉及的数百个基因之间的复杂相互作用（包括那些导致附带耐药性或易感性的相互作用）所带来的解释限制，以及区分相关突变与简单自然多态性的频繁困难。
