Genomic epidemiology of Ukraine conflict-associated Klebsiella pneumoniae reveals the emergence of a high-risk clone with a hybrid virulence-resistance plasmid vulnerable to lytic phages

Abstract

As antimicrobial resistance continues to rise and the development of new antimicrobials lags, we face an urgent threat where routine infections could become life-threatening. Armed conflicts, like Russias war on Ukraine, intensify this crisis by accelerating the emergence and spread of resistant organisms across regions and borders. Phage Support Ukraine (Phage Sp UKR) is a collaborative effort to provide phages targeting circulating pathogens in Ukraine for delivery of personalized phage therapies. Within this context, we received multidrug-resistant bacterial isolates belonging to a number of different species. We here focus on Klebsiella pneumoniae, the most concerning pathogen with regard to prevalence, virulence and antibiotic resistance. Among the K. pneumoniae isolates, we identified sequence types (ST) 39, 101, 147, 307 and 395, as well as a predominating clonal group--CG10146 (ST23 KL57), first detected in Moscow--carrying a hybrid virulence-resistance plasmid encoding NDM-1 and aerobactin. Over two years (2023-2025), this clonal group expanded and acquired pan-resistance. When tested in virulence assays, only one isolate (ST395) displayed hypervirulence in a Galleria mellonella though not in a mouse infection model. Several phages isolated from Ukrainian sewage were able to lyse these K. pneumoniae strains, including strains obtained from soldiers displaced in Belgium, Germany, and Latvia. Bacterial resistance was observed during in vitro testing. However, some phage-resistant isolates had mutations in virulence factors, including one that completely lost its hybrid plasmid, resulting in restored antibiotic susceptibility. Strategies like Phage Sp UKR are essential to prevent the selection, persistence, and global spread of these MDR clones.