Escherichia coli ST648 Chronically Infecting Patients with Cystic Fibrosis. An Approach to Eradication

Extraintestinal pathogenic Escherichia coli causes community-acquired and nosocomial pneumonia, and poses a risk of infection, especially for patients with impaired lung function, such as patients 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 compound, 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 E. coli ST648 isolated from long-term infected CF patients, describe AMR and virulence factors, and investigate the effect of CL-55 on 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 chromosome and in the composition and genes of the plasmidome. 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 E. coli ST648 in both the aggregate and intracellular states, which allows us to propose the use of Fluorothiazinone as a combinative therapy to facilitate eradication of pathogenic microorganisms in the respiratory tract of patients with CF.