Giuliano Simone, Fox Valeria, Ferin Sara, Martini Luca, Angelini Jacopo, Bulfoni Michela, Krpan Beatrice, Gualandi Nicolò, Moreal Chiara, Perno Carlo Federico, Bernaschi Paola, Di Gennaro Ciro, Arcamone Celeste, Turco Sara, Stanziola Maria Cristina, Manzi Rosa, Curcio Francesco, Pipan Corrado, Tascini Carlo
Infectious Diseases Clinic, Azienda Sanitaria Universitaria Friuli Centrale, 33100, Udine, Italy.
Multimodal Laboratory Medicine, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Sci Rep. 2025 Jul 1;15(1):21161. doi: 10.1038/s41598-025-07624-z.
The emergence of carbapenemase-producing represents a significant clinical challenge. Resistance mechanisms involve carbapenemase production, porin and efflux pump alterations, penicillin-binding protein (PBP) modifications, and biofilm formation. This study characterizes a KPC- and a concurrent isolate harboring the same resistance genes, with also exhibiting PBP3 mutations. Whole-genome sequencing and plasmid analysis identified an IncFII(K) plasmid carrying the gene. Both strains shared two resistance genes (, ). contained a single copy of on Tn, whereas carried two copies on separate Tn transposons. Plasmid reconstruction revealed high homology (99.85%) with plasmid pECAZ147_KPC and plasmid pKPC. This suggests that transposon-mediated transfer between the two strains may have occurred via the same plasmid. Moreover, harbored PBP3 mutations (A233T, I332V), which have been previously linked to increased ceftazidime MICs and two missense mutations in . Despite carrying two copies of the gene, along with and PBP3 mutations, our isolate did not exhibit a significant increase in ceftazidime/avibactam MIC. This phenomenon could be explained by avibactam’s ability to bind to PBP2, potentially compensating for the reduced binding of ceftazidime to the mutated PBP3.
The online version contains supplementary material available at 10.1038/s41598-025-07624-z.
产碳青霉烯酶菌株的出现是一个重大的临床挑战。耐药机制包括碳青霉烯酶的产生、孔蛋白和外排泵的改变、青霉素结合蛋白（PBP）的修饰以及生物膜的形成。本研究对一株携带相同耐药基因的KPC菌株和一株同时存在的菌株进行了表征，该菌株还表现出PBP3突变。全基因组测序和质粒分析鉴定出一个携带该基因的IncFII(K)质粒。两株菌株共有两个耐药基因（，）。菌株在Tn上含有一个单拷贝的，而菌株在不同的Tn转座子上携带两个拷贝。质粒重建显示与质粒pECAZ147_KPC和质粒pKPC具有高度同源性（99.85%）。这表明两株菌株之间转座子介导的转移可能是通过同一质粒发生的。此外，菌株存在PBP3突变（A233T，I332V），此前已发现这些突变与头孢他啶最低抑菌浓度（MIC）升高有关，并且在中存在两个错义突变。尽管携带两个拷贝的基因，以及和PBP3突变，但我们的菌株头孢他啶/阿维巴坦MIC并未显著升高。这种现象可以通过阿维巴坦与PBP2结合的能力来解释，这可能补偿了头孢他啶与突变的PBP3结合减少的情况。
在线版本包含可在10.1038/s41598-025-07624-z获取的补充材料。
