Voronina Olga L, Kunda Marina S, Ryzhova Natalia N, Ermolova Ekaterina I, Goncharova Elizaveta R, Koroleva Ekaterina A, Kapotina Lidia N, Morgunova Elena Yu, Amelina Elena L, Zigangirova Nailya A
N.F. Gamaleya National Research Center for Epidemiology and Microbiology, Ministry of Health of Russia, Gamaleya Str., 18, 123098 Moscow, Russia.
Pulmonology Research Institute Under FMBA of Russia, Orekhovy Boulevard, 28, Building 10, 115682 Moscow, Russia.
Int J Mol Sci. 2025 Sep 5;26(17):8650. doi: 10.3390/ijms26178650.
Extraintestinal pathogenic causes community-acquired and nosocomial pneumonia and poses a risk of infection, especially for patients with impaired lung function, such individuals with cystic fibrosis (CF). When chronic infection develops, eradication of the pathogen is difficult even with aggressive antibacterial therapy and targeted CF treatment. A new agent, Fluorthiazinone (CL-55), an inhibitor of bacterial virulence, was registered in Russia in 2024. The aim of our study was to characterize the genomes of ST648 isolated from long-term-infected CF patients, describe virulence factors, and investigate the effect of CL-55 on two CF isolates in vitro. Comparison of the genomes of hypermucoviscous isolates showed that, in the presence of a large number of core genes, the isolates have adaptive differences both in their chromosomes and the composition and genes of their plasmidomes. Both isolates formed mature biofilms on an abiotic surface and were able to survive and proliferate inside macrophages. CL-55 in in vitro experiments was effective in suppressing ST648 in both the aggregate and intracellular states, allowing us to propose the use of Fluorthiazinone as a combinative therapy to facilitate eradication of pathogenic microorganisms in the respiratory tract in patients with CF.
肠外致病性细菌可引起社区获得性肺炎和医院获得性肺炎，并带来感染风险，尤其是对于肺功能受损的患者，如囊性纤维化（CF）患者。当发生慢性感染时，即使采用积极的抗菌治疗和针对性的CF治疗，病原体的根除也很困难。一种新型药物氟噻嗪酮（CL-55），作为一种细菌毒力抑制剂，于2024年在俄罗斯注册。我们研究的目的是对从长期感染的CF患者中分离出的ST648菌株的基因组进行特征分析，描述其毒力因子，并研究CL-55在体外对两种CF分离株的影响。对高黏液性分离株的基因组比较表明，在存在大量核心基因的情况下，这些分离株在染色体以及质粒组的组成和基因方面都存在适应性差异。两种分离株都能在非生物表面形成成熟的生物膜，并且能够在巨噬细胞内存活和增殖。在体外实验中，CL-55在聚集态和细胞内状态下均能有效抑制ST648，这使我们建议将氟噻嗪酮用作联合治疗药物，以促进CF患者呼吸道中致病微生物的根除。
