Antibiotics Abuse Exacerbates Inflammation Through Outer Membrane Vesicles-Induced Pyroptosis in Multidrug-Resistant Klebsiella Pneumoniae Infection

Abstract

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.