Emergence and Expansion of a Carbapenem-Resistant Pseudomonas aeruginosa Clone Are Associated with Plasmid-Borne bla (KPC-2) and Virulence-Related Genes.
Emergence and Expansion of a Carbapenem-Resistant Pseudomonas aeruginosa Clone Are Associated with Plasmid-Borne bla (KPC-2) and Virulence-Related Genes.
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DOI：
10.1128/msystems.00154-21
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发表时间：
2021-05-18
期刊：
影响因子：
6.4
通讯作者：
Wu Z
中科院分区：
文献类型：
--
作者：
Hu Y;Liu C;Wang Q;Zeng Y;Sun Q;Shu L;Lu J;Cai J;Wang S;Zhang R;Wu Z
铜绿假单胞菌是一种主要的机会性病原体，也是引起卫生保健相关感染的主要细菌之一。碳青霉烯类药物是治疗由铜绿假单胞菌引起的严重感染最有效的抗菌药物。然而，我们最近的监测显示，耐碳青霉烯P. aeruginosa （CRPA）在中国浙江的患病率达到38.67%。通过分析2006年至2018年从患者身上收集的CRPA分离株，我们发现33%的CRPA分离株携带blaKPC-2基因，该基因对碳青霉烯类和其他β-内酰胺类具有高度耐药性。特别是，出现了一个CRPA克隆ST463（序列型463），并已成为群体中的优势CRPA克隆。基因组测序显示ST463扩增与质粒携带的blaKPC-2有关。blaKPC-2侧翼的移动元件、IV型分泌系统以及ST463克隆的成功扩增可能进一步促进了blaKPC-2在铜绿假单胞菌中的传播。分子钟分析表明，克隆ST463的出现时间约为2007年。全基因组关联分析显示，567个基因与ST463克隆相关，包括几个已知的与低脂寡糖（LOS） o抗原和外毒素生物合成相关的毒力基因。这些发现表明，ST463正在通过质粒传播的blaKPC-2和毒力相关基因在医院感染中扩大，未来应进行密切监测。卫生保健相关感染，也称为医院感染，是全世界卫生保健服务中最常见的不良事件，造成高发病率和死亡率以及高卫生保健费用。铜绿假单胞菌是导致卫生保健相关感染的主要细菌之一。碳青霉烯类是治疗其严重感染最有效的抗菌剂。然而，近年来耐碳青霉烯P. aeruginosa （CRPA）的患病率呈快速上升趋势，我们的监测显示，中国浙江省CRPA的患病率达到38.67%。近十年来对CRPA分离株的基因组测序表明，最近出现了一个CRPA克隆（ST463）。该克隆对β-内酰胺类，包括碳青霉烯类和氟喹诺酮类药物具有高度耐药性。全基因组关联分析显示，该克隆扩增出毒力相关基因和质粒携带的碳青霉烯耐药基因blaKPC-2。这些发现具有重要的公共卫生意义，因为这些信息将有助于控制和尽量减少CRPA医院感染。
Pseudomonas aeruginosa is a major opportunistic pathogen and one of the leading bacterial species causing health care-associated infections. Carbapenems are the most effective antimicrobial agents for the treatment of severe infections caused by P. aeruginosa. However, our recent surveillance demonstrated that the prevalence of carbapenem-resistant P. aeruginosa (CRPA) reached 38.67% in Zhejiang, China. By analyzing CRPA isolates collected from patients from 2006 to 2018, we found that 33% of CRPA isolates carried the gene blaKPC-2, which conferred high-level resistance to carbapenems and other β-lactams. In particular, a CRPA clone, ST463 (sequence type 463), emerged and has become the predominant CRPA clone among the population. Genome sequencing demonstrated that ST463 expansion was associated with plasmid-borne blaKPC-2. The mobile element flanking blaKPC-2, the type IV secretion system, and the successful expansion of clone ST463 might have further favored blaKPC-2 spread in P. aeruginosa. Molecular clock analysis dated the emergence of clone ST463 to around 2007. Genome-wide association analysis showed that 567 genes were associated with clone ST463, including several known virulence genes related to the biosynthesis of lipooligosaccharide (LOS) O-antigens and exotoxin. These findings indicate that ST463 is expanding with plasmid-borne blaKPC-2 and virulence-related genes in nosocomial infections, and close surveillance should be undertaken in the future. IMPORTANCE Health care-associated infections, also known as nosocomial infections, are the most frequent adverse events in health care delivery worldwide, causing high rates of morbidity and mortality and high health care costs. Pseudomonas aeruginosa is one of the leading bacterial species causing health care-associated infections. Carbapenems are the most effective antimicrobial agents for the treatment of its severe infections. However, the prevalence of carbapenem-resistant P. aeruginosa (CRPA) has been increasing rapidly in recent years, and our surveillance demonstrated that the prevalence of CRPA reached 38.67% in Zhejiang, China. Genome sequencing of CRPA isolates over a decade showed that a CRPA clone (ST463) emerged recently. The clone is highly resistant to β-lactams, including carbapenems, and fluoroquinolones. Genome-wide association analysis showed that the clone expanded with virulence-related genes and the plasmid-borne carbapenem-resistant gene blaKPC-2. These findings are of significant public health importance, as the information will facilitate the control and minimization of CRPA nosocomial infections.