ABSTRACT: Clinical samples from a genomic characterization of Carbapenem-non-susceptible Pseudomonas aeruginosa strains from two ICUs from the referral national hospital in Jakarta, Indonesia.
Project description:Clinical samples from a genomic characterization of Carbapenem-susceptible Pseudomonas aeruginosa strains from two ICUs from the referral national hospital in Jakarta, Indonesia.
Project description:Environmental samples from a genomic characterization of Carbapenem-non-susceptible Pseudomonas aeruginosa strains from two ICUs from the referral national hospital in Jakarta, Indonesia.
Project description:Unknown are the mechanisms of tolerance and persistence associated to several compounds in A.baumannii clinical isolates. Using transcriptomical and microbiological studies, we found a link between bacterial tolerance mechanisms to clorhexidine as well as the development of persistence in presence of imipenem in an A.baumannii strain belonging to ST-2 clinical clone (carbapenem-resistant with OXA-24 ß-lactamase and AbkAB TA system by plasmid). Interestingly, in A.baumannii ATCC17978 strain (carbapenem-susceptible isolate which carries AbkAB TA system by plasmid) showed persistence in presence of imipenem.
Project description:Sixteen paired matched samples from primary breast cancers and brain metastases diagnosed between April 1, 2001 and December 31, 2012 were collected from 8 institutions. Brain metastases were identified based on magnetic resonance imaging and/or computed tomography findings. The clinical characteristics of all the patients were obtained from their medical records. This study was approved by the institutional review board of each participating institute (Tokai University School of Medicine; National Hospital Organization Osaka National Hospital; Kinki University School of Medicine; Niigata Cancer Center Hospital; Shizuoka General Hospital; Hokkaido Cancer Center; National Hospital Organization, Tokyo Medical Center; and Gunma Prefectural Cancer Center). Matching primary breast cancers and brain metastases Formalin-Fixed Paraffin-Embedded (FFPE) specimens for gene expression analysis were collected into RNA. RNA from specimens was isolated, and quantity and quality of the each RNA was using an Agilent 2100 Bioanalyzer (Agilent Technologies). Genome-wide expression levels of transcripts were analyzed using the Affymetrix U133A gene chips (Affymetrix) according to the manufacture’s instructions.
Project description:In this study, we report the genome-wide expression profiles of hospital-acquired and community-acquired P. aeruignosa. The analysis of that provides crucial implications concerning the virulence determinants associated with the community-acquired diarrheagenic strain of P. aeruginosa
Project description:Pseudomonas aeruginosa is a leading cause of hospital acquired infections for which the development of new antibiotics is urgently needed. Unlike most enteric bacteria, P. aeruginosa lacks thymidine kinase and thymidine phosphorylase activity, and thus cannot scavenge exogenous thymine. An appealing strategy to selectively target P. aeruginosa while leaving the healthy microbiome largely intact would thus be to disrupt thymidine synthesis while providing exogenous thymine. However, this approach was previously intractable because known antibiotics that perturb thymidine synthesis are largely inactive against P. aeruginosa. Here, we characterize a novel dihydrofolate reductase inhibitor, fluorofolin, that exhibits significant activity against P. aeruginosa in culture and in a mouse thigh infection model. Fluorofolin is active against a wide range of clinical P. aeruginosa isolates resistant to known antibiotics, including critical antibiotic development priorities expressing the beta-lactamases KPC-5 and NDM-1. Importantly, in the presence of thymine supplementation, fluorofolin activity is selective for P. aeruginosa. Resistance to fluorofolin can emerge through overexpression of the efflux pumps MexCD-OprJ and MexEF-OprN. However, these mutants also decrease pathogenesis, in part due to increased export of quorum sensing precursors leading to decreased virulence factor production. Our findings thus demonstrate how understanding species-specific genetic differences and discovery of an antibiotic with a widely conserved target can enable selective targeting of important pathogens while revealing new tradeoffs between resistance and pathogenesis.
Project description:Pseudomonas aeruginosa is a predominant pathogen in chronic lung infections in individuals with cystic fibrosis (CF). Epidemic strains of P. aeruginosa, such as the Liverpool Epidemic Strain (LES), are capable of transferring between CF patients and have been associated with increased hospital visits and antibiotic treatments. We used label-free quantitative proteomics to compare the laboratory strain PAO1, beta-lactam resistant isolate LESB58, and beta-lactam susceptible isolate LESlike1 and their responses to three beta-lactams (aztreonam, carbenicillin, piperacillin), the aminoglycoside tobramycin, and hydrogen peroxide. Across all samples, we identified 3019 proteins with a minimum of two peptides. We found that LESB58 showed a large response to treatment with the beta-lactam carbenicillin, with 644 proteins significantly increased in abundance and 590 proteins significantly decreased in abundance (Students t-test, p≤0.05, FDR=0.05, S0=1). Proteomic characterization of an additional beta-lactam resistant isolate, LES431, exposed to carbenicillin showed that this response was shared by both isolates. Part of the response to carbenicillin in LESB58 included an increase in abundance in proteins involved in cell wall synthesis and division.