Fang Jianhua, Liu Qiong, Chen Huade, Lai Hongyi, Huang Jingyi, Li Jiayue, Xu Yilin, Cheng Na, Xiang Tianxin
Jiangxi Provincial Key Laboratory of Prevention and Treatment of Infectious Diseases, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330052, People's Republic of China.
Infectious Disease Department, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330052, People's Republic of China.
Infect Drug Resist. 2025 Aug 29;18:4499-4511. doi: 10.2147/IDR.S534712. eCollection 2025.
(KP) is a common Gram-negative bacterium in clinical practice and can cause various infectious diseases, including pneumonia, liver abscess and bloodstream infection. Carbapenem-resistant (CRKP) has become a major threat to global health due to its high incidence and mortality rates, especially the ST11-CRKP strain prevalent in China.
The age, main clinical diagnosis, previous health and immune status of the two patients with ST11-CRKP-related infections during the same period reported in this study were similar.
The antibiotic treatment regimens for the two patients were the same in terms of the type and dosage of antibiotics, except for omadacycline. Meanwhile, PFGE, multilocus sequence typing (MLST), and K typing confirmed that the two strains had the same genetic background. Through experiments on serum resistance, biofilm formation, the infection model and the hypermucus phenotype, it was found that CRKP1 showed a hypervirulent phenotype, while CRKP15 showed a hopervirulent phenotype. Whole-genome sequencing further revealed the differences in virulence genes between the two strains and further confirmed the virulence phenotypes of the two strains. Single nucleotide polymorphism (SNP) analysis showed that the gene was one of the key genes for the virulence difference of the two strains with the same genetic background under the therapeutic difference of omadacycline. In addition, the effect of omadacycline on the expression of the gene was evaluated by qRT-PCR technology. The interaction between the gene and omadacycline was confirmed through molecular docking.
To sum up, these findings suggest that under the therapeutic stress of omadacycline, CRKP may adjust virulence through adaptive evolution, and the gene may be the key factor for the differences in virulence within this bacterial population.
肺炎克雷伯菌（KP）是临床实践中常见的革兰氏阴性菌，可引起多种感染性疾病，包括肺炎、肝脓肿和血流感染。耐碳青霉烯类肺炎克雷伯菌（CRKP）因其高发病率和死亡率，已成为全球健康的重大威胁，尤其是在中国流行的ST11-CRKP菌株。
本研究报告的同期两名ST11-CRKP相关感染患者的年龄、主要临床诊断、既往健康和免疫状态相似。
两名患者的抗生素治疗方案在抗生素类型和剂量方面相同，除了奥玛环素。同时，脉冲场凝胶电泳（PFGE）、多位点序列分型（MLST）和K分型证实这两个菌株具有相同的遗传背景。通过血清抗性、生物膜形成、感染模型和高黏液表型实验，发现CRKP1表现出高毒力表型，而CRKP15表现出低毒力表型。全基因组测序进一步揭示了两个菌株之间毒力基因的差异，并进一步证实了两个菌株的毒力表型。单核苷酸多态性（SNP）分析表明，在奥玛环素治疗差异下，该基因是具有相同遗传背景的两个菌株毒力差异的关键基因之一。此外，通过qRT-PCR技术评估了奥玛环素对该基因表达的影响。通过分子对接证实了该基因与奥玛环素之间的相互作用。
综上所述，这些发现表明，在奥玛环素的治疗压力下，CRKP可能通过适应性进化来调节毒力，并且该基因可能是该细菌群体中毒力差异的关键因素。
