Exposure to ceftazidime-avibactam induced antimicrobial resistance and enhanced virulence in a Klebsiella pneumoniae strain.

To prevent and control the emergence of ceftazidime-avibactam (CZA) resistance, unraveling its underlying mechanisms is critical. Accordingly, in this study, MDR Klebsiella pneumoniae (KP) strain (C357) was subjected to repeated in vitro exposure to CZA until resistance emerged. C357 acquired CZA resistance by the 15th generation (C357-15). On further assessing the fitness cost and potential mechanisms of resistance, C357-15 demonstrated significantly enhanced biofilm-forming capacity and elevated virulence. Moreover, the genes encoding type 3 fimbriae (i.e., mrkA, mrkB, mrkC, and mrkD) and quorum-sensing (QS) system-associated genes (i.e., lsrR) in C357-15 were upregulated. Notably, QS inhibitors significantly decreased the expression of type 3 fimbriae genes of C357-15. Thus, prolonged exposure to CZA induced both biofilm-forming ability and enhanced virulence in MDR-KP. Moreover, QS may promote the expression of type 3 fimbriae-related genes. In conclusion, QS may promote biofilm formation and enhance virulence either directly or by influencing type 3 fimbriae-related gene expression.