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 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:Expression array data was used to compare parental FGFR3-TACC3 fusion-driven urothelial cell lines with their FGFR inhibitor-resistant derivatives. In this dataset, we include RT112 and RT4 parental cells, RT112 cells acutely treated with PD173074 (24 h), RT112 and RT4 resistant derivatives cultured with drug and their resistant derivatives cultured for four to six passages out of drug.