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 <i>Klebsiella pneumoniae</i> (KP) strain (C357) was subjected to repeated <i>in vitro</i> exposure to CZA until resistance emerged. C357 acquired CZA resistance by the 15^th 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., <i>mrkA</i>, <i>mrkB</i>, <i>mrkC</i>, and <i>mrkD</i>) and quorum-sensing (QS) system-associated genes (i.e., <i>lsrR</i>) 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.