Che Meiyao, Fresno Ana Herrero, Calvo-Fernandez Cristina, Hasman Henrik, Kurittu Paula E, Heikinheimo Annamari, Hansen Lisbeth Truelstrup
National Food Institute, Technical University of Denmark, 2800 Lyngby, Denmark.
Department of Biochemistry and Molecular Biology, Faculty of Sciences, Campus Terra, Universidade da Santiago de Compostela (USC), 27002 Lugo, Spain.
Antibiotics (Basel). 2024 Apr 10;13(4):349. doi: 10.3390/antibiotics13040349.
carrying IncK- plasmids mediating resistance to extended-spectrum cephalosporins (ESC) has been frequently described in food-producing animals and in humans. This study aimed to characterize IncK--positive ESC-resistant isolates from poultry production systems in Denmark, Finland, and Germany, as well as from Danish human blood infections, and further compare their plasmids. Whole-genome sequencing (Illumina) of all isolates ( = 46) confirmed the presence of the gene. Minimum inhibitory concentration (MIC) testing revealed a resistant phenotype to cefotaxime as well as resistance to ≥3 antibiotic classes. Conjugative transfer of the gene confirmed the resistance being on mobile plasmids. Pangenome analysis showed only one-third of the genes being in the core with the remainder being in the large accessory gene pool. Single nucleotide polymorphism (SNP) analysis on sequence type (ST) 429 and 1286 isolates showed between 0-60 and 13-90 SNP differences, respectively, indicating vertical transmission of closely related clones in the poultry production, including among Danish, Finnish, and German ST429 isolates. A comparison of 22 ST429 isolates from this study with 80 ST429 isolates in Enterobase revealed the widespread geographical occurrence of related isolates associated with poultry production. Long-read sequencing of a representative subset of isolates ( = 28) allowed further characterization and comparison of the IncK- plasmids with publicly available plasmid sequences. This analysis revealed the presence of highly similar plasmids in ESC-resistant from Denmark, Finland, and Germany pointing to the existence of common sources. Moreover, the analysis presented evidence of global plasmid transmission and evolution. Lastly, our results indicate that IncK- plasmids and their carriers had been circulating in the Danish production chain with an associated risk of spreading to humans, as exemplified by the similarity of the clinical ST429 isolate to poultry isolates. Its persistence may be driven by co-selection since most IncK- plasmids harbor resistance factors to drugs used in veterinary medicine.
携带介导对超广谱头孢菌素(ESC)耐药的IncK - 质粒的情况在食用动物和人类中已有频繁报道。本研究旨在对来自丹麦、芬兰和德国家禽生产系统以及丹麦人类血液感染中的IncK - 阳性ESC耐药菌株进行特征分析,并进一步比较它们的质粒。对所有分离株(n = 46)进行全基因组测序(Illumina)证实了blaCTX-M基因的存在。最低抑菌浓度(MIC)测试显示对头孢噻肟耐药表型以及对≥3类抗生素耐药。blaCTX-M基因的接合转移证实耐药性存在于可移动质粒上。泛基因组分析表明只有三分之一的基因位于核心区域,其余基因存在于大型辅助基因库中。对序列型(ST)429和1286分离株的单核苷酸多态性(SNP)分析分别显示0 - 60和13 - 90个SNP差异,表明在家禽生产中密切相关克隆的垂直传播,包括丹麦、芬兰和德国的ST429分离株之间。将本研究中的22株ST429分离株与Enterobase中的80株ST429分离株进行比较,发现与家禽生产相关的相关分离株在地理上广泛存在。对一部分代表性分离株(n = 28)进行长读长测序,能够进一步对IncK - 质粒与公开可用的质粒序列进行特征分析和比较。该分析揭示在来自丹麦、芬兰和德国的ESC耐药菌株中存在高度相似的质粒,表明存在共同来源。此外,该分析提供了全球质粒传播和进化的证据。最后,我们的结果表明IncK - 质粒及其携带菌株在丹麦生产链中传播,存在传播给人类的相关风险,临床ST429分离株与家禽分离株的相似性就是例证。其持续存在可能是由共选择驱动的,因为大多数IncK - 质粒携带对兽用药物的耐药因子。
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