摘要
      据报道，铜绿假单胞菌ST308克隆携带碳青霉烯酶基因，如blaIMP和blaVIM，但很少与blaNDM-1相关。使用全基因组测序对2019年4月至2020年11月期间从新加坡一家三级护理医院获得的199株铜绿假单胞菌ST308临床和环境分离株进行了表征。此外，还纳入了来自新加坡另外两家地方三级护理医院的71个blaNDM-1阳性ST308全基因组序列和公共数据库中的83个全球blaNDM-1-阴性ST308全基因序列，以评估系统发育关系并进行基因组分析。系统发育分析和差异时间估计显示，blaNDM-1阳性铜绿假单胞菌ST308于2005年被引入新加坡（95 % 最高后密度：2001年至2008年）。所有局部blaNDM-1阳性ST308分离株的核心基因组、抗性组和分析显示，多个抗生素抗性基因（ARGs）[aac（3）-Id、aac（6′）-Il、aadA6、aadA11、dfrB5、msr（E）、floR、sul2和qnrVC1]的染色体整合，而这些基因在全局blaNDM-1-阴性ST308序列中不存在。大多数ARGs和毒力基因在来自三个不同的地方医院的分离株中是保守的。blaNDM-1阳性ST308临床和环境分离株的密切遗传相关性表明，医院环境和人类宿主之间存在共循环，医院环境是潜在的宿主。核心基因组单核苷酸多态性分析显示，blaNDM-1阳性ST308分离株可能在三家医院之间7岁以上的克隆传播 年。在95个临床分离株中，有6个（6.3%）为血流分离株。这项研究报告了十多年前在新加坡引入的致病性blaNDM-1阳性铜绿假单胞菌ST308，并有必要进行监测以更广泛地传播。
ABSTRACT
Pseudomonas aeruginosa ST308 clone has been reported to carry carbapenemase genes such as blaIMP and blaVIM but has been rarely associated with blaNDM-1. A total of 199 P. aeruginosa ST308 clinical and environmental isolates obtained between April 2019 and November 2020 from a tertiary-care hospital in Singapore were characterized using whole-genome sequencing. In addition, 71 blaNDM-1-positive ST308 whole-genome sequences from two other local tertiary-care hospitals in Singapore and 83 global blaNDM-1-negative ST308 whole-genome sequences in public databases were included to assess phylogenetic relationships and perform genome analyses. Phylogenetic analysis and divergent time estimation revealed that blaNDM-1-positive P. aeruginosa ST308 was introduced into Singapore in 2005 (95 % highest posterior density: 2001 to 2008). Core genome, resistome, and analyses of all local blaNDM-1-positive ST308 isolates showed chromosomal integration of multiple antibiotic resistance genes (ARGs) [aac(3)-Id, aac(6′)-Il, aadA6, aadA11, dfrB5, msr(E), floR, sul2, and qnrVC1], which was absent in global blaNDM-1-negative ST308 sequences. Most ARGs and virulence genes were conserved across isolates originating from the three different local hospitals. Close genetic relatedness of the blaNDM-1-positive ST308 clinical and environmental isolates suggests cocirculation between the hospital environment and human hosts with the hospital environment as a potential reservoir. Core genome single nucleotide polymorphism analyses revealed possible clonal transmission of blaNDM-1-positive ST308 isolates between the three hospitals over 7 years. Bloodstream isolates accounted for six of 95 (6.3%) clinical isolates. This study reports the introduction of a pathogenic blaNDM-1-positive P. aeruginosa ST308 more than a decade ago in Singapore and warrants surveillance for wider dissemination.

https://journals.asm.org/doi/full/10.1128/spectrum.04033-22