Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain AJ218.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain KPC2.
Project description:With the global increase in the use of carbapenems, several gram-negative bacteria have acquired carbapenem resistance, thereby limiting treatment options. Klebsiella pneumoniae is one of such notorious pathogen that is being widely studied to find novel resistance mechanisms and drug targets. These antibiotic-resistant clinical isolates generally harbor many genetic alterations, and identification of causal mutations will provide insights into the molecular mechanisms of antibiotic resistance. We propose a method to prioritize mutated genes responsible for antibiotic resistance, in which mutated genes that also show significant expression changes among their functionally coupled genes become more likely candidates. For network-based analyses, we developed a genome-scale co-functional network of K. pneumoniae genes, KlebNet (www.inetbio.org/klebnet). Using KlebNet, we could reconstruct functional modules for antibiotic-resistance, and virulence, and retrieved functional association between them. With complementation assays with top candidate genes, we could validate a gene for negative regulation of meropenem resistance and four genes for positive regulation of virulence in Galleria mellonella larvae. Therefore, our study demonstrated the feasibility of network-based identification of genes required for antimicrobial resistance and virulence of human pathogenic bacteria with genomic and transcriptomic profiles from antibiotic-resistant clinical isolates.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to Klebsiella pneumoniae complex strains AJ055, AJ218, AJ292, KPC2, 03-311-0071 and 04153260899A.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pneumoniae and Streptococcus pyogenes, 5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. This submission contains the results from six Klebsiella strains (four Klebsiella variicola: AJ005, AJ292, 03-311-0071, 04153260899A and two Klebsiella pneumoniae: AJ218, KPC2) grown in either RPMI or pooled human sera. Six replicates of each condition were subjected to shotgun proteomics and label-free MS1-based quantitation.
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:The increasing antibiotic resistance of Klebsiella pneumoniae poses a serious threat to global public health. To investigate the antibiotic resistance mechanism of Klebsiella pneumonia, we performed gene expression profiling analysis using RNA-seq data for clinical isolates of Klebsiella pneumonia, KPN16 and ATCC13883. Our results showed that mutant strain KPN16 is likely to act against the antibiotics through increased increased butanoate metabolism and lipopolysaccharide biosynthesis, and decreased transmembrane transport activity.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain AJ055.
Project description:The Antibiotic Resistant Sepsis Pathogens Framework Initiative aims to develop a framework dataset of 5 sepsis pathogens (5 strains each) using an integrated application of genomic, transcriptomic, metabolomic and proteomic technologies. The pathogens included in this initiative are: Escherichia coli, Klebsiella pneumoniae complex, Staphylococcus aureus, Streptococcus pyogenes, and Streptococcus pneumoniae. This submission pertains to strain 04153260899A.
