Virulence comparison and pathological impacts of three clinical Klebsiella pneumoniae isolates in a zebrafish larval model

Klebsiella pneumoniae (Kp) can cause infections in communities and hospitals. After a report of a first highly virulent strain, it has now become the important pathogens that threatens human health and can often infect patients in intensive care units (ICUs). Kp is invasive and causes damage to the liver, pancreas, blood, intestines, and even the central nervous system. Zebrafish is a model organism with many advantages in biomedicine, and it has been used as a host to evaluate the virulence of Kp. However, there are no reports using zebrafish as a host to study the pathological characteristics of Kp. In this study, three Kp strains (KP1053, KP1196, and KP1195) were isolated from two clinical patients. The genetic and drug-susceptibility properties of the strains were first studied, and then zebrafish was used as a host to evaluate their virulence and pathogenicity. The three clinical Kp strains led to a marked decrease in the zebrafish survival rate, heart rate, and swimming distance; they also impeded the development of the swim bladder and resulted in a notable increase in the number of inflammatory cells. The virulence of these three strains followed the sequence KP1196 > KP1053 > KP1195. The transcriptome analysis found that lung, liver, nerve, and other developmental processes were significantly enriched in differentially expressed genes (DEGs), indicating that Kp may affect organ pathology through these genes. Our research offers a valuable reference for comprehending the pathological mechanisms underlying Kp clinical isolates.