Antibiotics are powerful drugs used in the treatment of bacterial infections. The inappropriate use of these medicines has driven the emergence and dissemination of antibiotic resistance (AR) in most bacteria. Pseudomonas aeruginosa is an opportunistic pathogen commonly involved in environmental- and difficult-to-treat hospital-acquired infections. This species is frequently resistant to several antibiotics, being in the “critical” category of the WHO's priority pathogens list for research and development of new antibiotics. In addition to a remarkable intrinsic resistance to several antibiotics, P. aeruginosa can acquire resistance through chromosomal mutations and acquisition of AR genes. P. aeruginosa has one of the largest bacterial genomes and possesses a significant assortment of genes acquired by horizontal gene transfer (HGT), which are frequently localized within integrons and mobile genetic elements (MGEs), such as transposons, insertion sequences, genomic islands, phages, plasmids and integrative and conjugative elements (ICEs). This genomic diversity results in a non-clonal population structure, punctuated by specific clones that are associated with significant morbidity and mortality worldwide, the so-called “high-risk clones”. Acquisition of MGEs produces a fitness cost in the host, that can be eased over time by compensatory mutations during MGE-host coevolution. Even though plasmids and ICEs are important drivers of AR, the underlying evolutionary traits that promote this dissemination are poorly understood. In this review, we provide a comprehensive description of the main strategies involved in AR in P. aeruginosa and the leading drivers of HGT in this species. The most recently developed genomic tools that allowed a better understanding of the features contributing for the success of P. aeruginosa are discussed.

抗生素是用于治疗细菌感染的有力药物。这些药物的不当使用已导致大多数细菌中抗生素抗性（AR）的出现和传播。铜绿假单胞菌是机会病原体，通常与环境和难以治疗的医院获得性感染有关。该物种通常对几种抗生素具有抗药性，在世卫组织研究和开发新抗生素的优先病原体清单中属于“关键”类别。除了对几种抗生素的显着内在抗药性外，铜绿假单胞菌还可以通过染色体突变和获得AR基因获得抗药性。铜绿假单胞菌具有最大的细菌基因组之一，并具有通过水平基因转移（HGT）获得的大量基因，这些基因通常位于整合子和移动遗传元件（MGE）内，例如转座子，插入序列，基因组岛，噬菌体，质粒以及整合和共轭元素（ICE）。这种基因组多样性导致了一个非克隆的种群结构，被特定的克隆所打断，这些克隆与全世界的高发病率和死亡率相关，即所谓的“高风险克隆”。获得MGE会在宿主体内产生适应性成本，随着MGE-宿主协同进化过程中的补偿性突变，随着时间的流逝，其成本可以降低。即使质粒和ICEs是AR的重要驱动因素，促进这种传播的潜在进化特征仍知之甚少。在这篇评论中，铜绿假单胞菌和HGT在该物种中的主要驱动力。讨论了最近开发的基因组工具，可以更好地了解有助于铜绿假单胞菌成功的特征。