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Drug resistance of Klebsiella pneumoniae severely threatens human health. Overcoming the mechanisms of K. pneumoniae resistance to develop novel vaccines against drug-resistant K. pneumoniae is highly desired. Here, we report a technology platform that uses high pressure to drive drug-resistant K. pneumoniae to pass through a gap, inducing the formation of stable artificial bacterial biomimetic vesicles (BBVs). These BBVs had little to no bacterial intracellular protein or nucleic acid and had high yields. BBVs were efficiently taken up by dendritic cells to stimulate their maturation. BBVs as K. pneumoniae vaccines had the dual functions of inducing bacteria-specific humoral and cellular immune responses to increase animals' survival rate and reduce pulmonary inflammation and bacterial loads. We believe that BBVs are new-generation technology for bacterial vesicle preparation. Establishment of this BBV vaccine platform can maximally expand preparation technology for vaccines against drug-resistant K. pneumoniae.

Summary The inappropriate use of antibiotics is a severe public health problem worldwide, contributing to the emergence of multidrug-resistant (MDR) bacteria. To explore the possible impacts of the inappropriate use of antibiotics on the immune system, we use Klebsiella pneumoniae (K. pneumoniae) infection as an example and show that imipenem increases the mortality of mice infected by MDR K. pneumoniae. Further studies demonstrate that imipenem enhances the secretion of outer membrane vesicles (OMVs) with significantly elevated presentation of GroEL, which promotes the phagocytosis of OMVs by macrophages that depends on the interaction between GroEL and its receptor, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). OMVs cause the pyroptosis of macrophages and the release of proinflammatory cytokines, which contribute to exacerbated inflammatory responses. We propose that the inappropriate use of antibiotics in the cases of infection by MDR bacteria such as K. pneumoniae might cause damaging inflammatory responses, which underlines the pernicious effects of inappropriate use of antibiotics.

The abuse of antibiotics is a severe public health problem worldwide, contributing to the emergence of multidrug-resistant (MDR) bacteria. To explore the possible impacts of antibiotic abuse on the immune system, here, using Klebsiella pneumoniae (K. pneumoniae) infection as an example, we showed that imipenem, a carbapenem antibiotic, increased the mortality of mice infected by MDR K. pneumoniae. Further studies demonstrated that imipenem enhanced the secretion of outer membrane vesicles (OMVs) with significantly elevated presentation of GroEL, which promoted the phagocytosis of OMVs by macrophages depending on the interaction between GroEL and its receptor LOX-1. OMVs cause the pyroptosis of macrophages and release of proinflammatory cytokines, which contribute to exacerbated inflammatory responses. We proposed that antibiotic abuse in cases of infection by MDR bacteria might cause severe inflammatory damage, which underlines the perniciousness of antibiotic abuse on the immune system.