Project description: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 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 antibiotic.
Project description:Efflux of antimicrobial compounds from bacterial cells is one of the important mechanisms responsible for multi-drug resistance (MDR). Inhibiting the activity of efflux pumps using chemosensitizers like 1-(1-naphthylmethyl)-piperazine (NMP) is currently considered as a promising strategy to overcome MDR. However, additional effects of NMP other than inhibition are rarely if ever considered. Here, using phenotypic, phenotypic microarray and transcriptomic assays we show that NMP plays a role in membrane destabilization in MDR Klebsiella pneumoniae MGH 78578 strain. The observation of membrane destabilization was supported by RNA-seq data which showed that many up-regulated genes were either directly involved in responses to envelope stress or bacterial repair systems which are essential to maintain viability in an environment containing NMP. Membrane destabilization happens as early as 15 minutes post-NMP treatment. We postulate that the early membrane disruption leads to destabilization of inner membrane potential, impairing ATP production and consequently resulting in efflux pump inhibition.
Project description:Transcriptional profiling of K. pneumoniae comparing the wild type strain (S5) with a hfq deletion mutant (H0201). Goal was to determine the effects of Hfq absence on global K. pneumoniae gene expression.
Project description:Transcriptional profiling of K. pneumoniae comparing the wild type strain (S5) with a hfq deletion mutant (H0201). Goal was to determine the effects of Hfq absence on global K. pneumoniae gene expression. WT vs. Hfq mutant. Eight replicates for each ORF presented in the 44K array.
Project description:The transcriptional, epigenomic, and genomic profiles of K. pneumoniae isolates were characterised to identify novel colistin and carbapenem resistance mechanisms. The genomic DNA and total RNA of the isolates were isolated and sequenced on PacBio.
