Development of a bacterial infection model in zebrafish embryos with special focus on colistin-resistant Klebsiella pneumoniae

Sammanfattning: Zebrafish (Danio rerio) is a promising model organism for immunological studies. A time window between the development of the innate and adaptive immune system makes it possible to investigate the mechanisms originating exclusively from the innate immune system. Moreover, zebrafish shows many similarities with the mammalian immune system and has counterparts for most of the human immune cells. Here we aim to develop a model system to study host-pathogen interaction between Klebsiella pneumoniae and zebrafish embryos. According to our results, zebrafish develops reliable systematic infection as a result of microinjection in the yolk sac. Moreover, the expression of immune and inflammation related genes are similar to the mammalian immune response. Klebsiella pneumoniae is an important pathogen, especially because of its ability to possess a wide repertoir of carbapenemases, conferring resistance against numerous antibiotics, including colistin, a last-resort drug. Colistin resistance is based on the modification of lipid A, as a result of inactivation of the mgrB gene. Since colistin and our own antimicrobial peptides show the same mechanism of action, development of cross-resistance is a serious threat. A previous study suggested that colistin resistance may cause increase in virulence. However, recent data from our group showed that even though cross-resistance was detectable between colistin and LL-37 in bacterial cultures, the inactivation of mgrB gene did not cause any differences in virulence and bacterial survival in human blood or serum. The zebrafish model supported this finding with showing that there is no significant difference between colistin-resistant and colistin-susceptible Klebsiella pneumoniae strains with regard to bacterial growth and survival of zebrafish embryos.