Project description:Klebsiella pneumoniae is an arising threat to human health. However, host immune responses in response to this bacterium remain to be elucidated. The goal of this study was to identify the dominant host immune responses associated with Klebsiella pneumoniae pulmonary infection. Pulmonary mRNA profiles of 6-8-weeks-old BALB/c mice infected with/without Klebsiella pneumoniae were generated by deep sequencing using Illumina Novaseq 6000. qRT–PCR validation was performed using SYBR Green assays. Using KEGG (Kyoto Encyclopedia of Genes and Genomes) analysis, we identified several immune associated pathways, including complement and coagulation cascades, Toll-like receptor signaling pathway, Rap1 signaling pathway, chemokine signaling pathway, TNF signaling pathway, phagosome and NOD-like receptor signaling pathway, were involved in Klebsiella pneumoniae pulmonary infection. Using ICEPOP (Immune CEll POPulation) analysis, we found that several cell types were involved in the host immune response to Klebsiella pneumoniae pulmonary infection, including dendritic cells, macrophages, monocytes, NK (natural killer) cells, stromal cells. Further, IL-17 chemokines were significantly increased during Klebsiella pneumoniae infection. This study provided evidence for further studying the pathogenic mechanism of Klebsiella pneumoniae pneumonia infection.
Project description:To investigate the molecular mechanisms mediating activation of human circulating MAIT cells during infection with Klebsiella pneumoniae and compare the transcriptomics with cells activated by type-I interferons or influenza virus
Project description:The interactions between Gram-negative respiratory pathogens and the host environment at the site of infection largely unknown. Pulmonary surfactant serves as an initial point of contact for inhaled bacteria entering the lung and is thought to contain molecular cues that aid colonization and pathogenesis. To gain insight into this ecological transition, we characterized the transcriptional responses of Pseudomonas aeruginosa PA14, Burkholderia thailandensis E264, Klebsiella pneumoniae MGH 78578, and Stenotrophomonas maltophilia K279A exposed to purified pulmonary surfactant (Survanta) through microarrays. This study provides novel insight into the interactions occurring between Gram-negative opportunistic pathogens and the host at an important infection site, and demonstrates the utility of purified lung surfactant preparations for dissecting host-lung pathogen interactions in vitro. The goal of this study was to compare the transcriptional responses of Pseudomonas aeruginosa PA14, Burkholderia thailandensis E264, Klebsiella pneumoniae MGH 78578, and Stenotrophomonas maltophilia K279A exposed to pulmonary surfactant using a custom affymetrix chip designed for their genomes. The goal of this study was to compare the transcriptional responses of Pseudomonas aeruginosa PA14, Burkholderia thailandensis E264, Klebsiella pneumoniae MGH 78578, and Stenotrophomonas maltophilia K279A exposed to pulmonary surfactant using a custom affymetrix chip designed for their genomes.
Project description:Klebsiella pneumoniae belongs to the group of bacterial pathogens causing the majority of antibiotic-resistant nosocomial infections worldwide; however, the molecular mechanisms underlying post-translational regulation of its physiology are poorly understood. Here we perform a comprehensive analysis of Klebsiella phosphoproteome, focusing on HipA, a Ser/Thr kinase involved in antibiotic tolerance in Escherichia coli. We show that overproduced K. pneumoniae HipA (HipAkp) is toxic to both E. coli and K. pneumoniae and its toxicity can be rescued by overproduction of the antitoxin HipBkp. Importantly, HipAkp overproduction leads to increased tolerance against ciprofloxacin, a commonly used antibiotic in the treatment of K. pneumoniae infections. Proteome and phosphoproteome analyses in the absence and presence of ciprofloxacin confirm that HipAkp has Ser/Thr kinase activity, auto-phosphorylates at S150, and shares multiple substrates with HipAec, thereby providing a valuable resource to clarify the molecular basis of tolerance and the role of Ser/Thr phosphorylation in this human pathogen.
Project description:This file comprises RNA-Seq data from the livers of mice challenged with acute intrapulmonary Klebsiella pneumoniae infection followed 1 h later with either storage-damaged RBC (stressed RBC) or young RBC. The livers were harvested from mice in both groups 24 h post-infection.
Project description:Antibiotic use can lead to expansion of multi-drug resistant pathobionts within the gut microbiome that can cause life-threatening infections. Selective alternatives to conventional antibiotics are in dire need. Here, we describe a Klebsiella PhageBank that enables the rapid design of antimicrobial bacteriophage cocktails to treat multi-drug resistant Klebsiella pneumoniae. Using a transposon library in carbapenem-resistant K. pneumoniae, we identified host factors required for phage infection in major Klebsiella phage families. Leveraging the diversity of the PhageBank and experimental evolution strategies, we formulated combinations of phages that minimize the occurrence of phage resistance in vitro. Optimized bacteriophage cocktails selectively suppressed the burden of multi-drug resistant K. pneumoniae in the mouse gut microbiome and drove bacterial populations to lose key virulence factors that act as phage receptors. Further, phage-mediated diversification of bacterial populations in the gut enabled co-evolution of phage variants with higher virulence and a broader host range. Altogether, the Klebsiella PhageBank represents a roadmap for both phage researchers and clinicians to enable phage therapy against a critical multidrug-resistant human pathogen.
Project description:This SuperSeries is composed of the following subset Series: GSE35746: Comparative analysis of regulatory elements between Escherichia coli and Klebsiella pneumoniae by genome-wide transcription start site profiling [tiling arrays] GSE35821: Comparative analysis of regulatory elements between Escherichia coli and Klebsiella pneumoniae by genome-wide transcription start site profiling [TSS-Seq] Refer to individual Series
Project description:To investigate the whole-genome gene expression difference between the wild-type and capsule deletion mutant in Klebsiella pneumoniae MGH 78578. The mutants analyzed in this study are further described in Huang T.W., Stapleton J.C., Chang H.Y., Tsai S.F., Palsson B.O., Charusanti P. Capsule removal via lambda-Red knockout system perturbs biofilm formation and fimbriae extression in Klesiella pneumoniae MGH 78578 (manuscript submission) A six chip study using total RNA recovered from three separate wild-type cultures and three separate cultures of a capsule deltion mutant of Klebsiella pneumoniae MGH 78578. The capsule gene cluster (KPN_02493 to KPN_02515) was entirely removed in the capsule deletion mutant. Each chip measures the expression level of 5,305 genes from Klebsiella pneumoniae MGH 78578 and the associated five plasmids (pKPN3, pKPN4, pKPN5, pKPN6 and pKPN7) with 50-mer oligo tiling array with 30-mer spacer.
Project description:Gene expression comparison between human colonic epithelial cells cultured with Klebsiella pneumoniae (KP) derived from PSC patients versus KP JCM1662.