Ontology highlight
ABSTRACT:
PROVIDER: PRJNA591264 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The emergence of colistin resistance in carbapenem-resistant and extended-spectrum ß-lactamase (ESBL)-producing bacteria is a significant threat to human health, and new treatment strategies are urgently required. Here we investigated the ability of the safe-for-human use ionophore PBT2 to restore antibiotic sensitivity in several polymyxin-resistant, ESBL-producing, carbapenem resistant Gram-negative human pathogens. PBT2 was observed to resensitize Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa to last-resort polymyxin class antibiotics, including a ‘next generation’ polymyxin derivative, FADDI-287. To gain additional insight into the potential mechanism of action of PBT2, we analyzed the transcriptome of K. pneumoniae and E. coli in the presence of sub-inhibitory concentrations of PBT2. Treatment with PBT2 was associated with multiple stress responses in both K. pneumoniae and E. coli. Significant changes in the transcription of transition metal ion homeostasis genes were observed in both strains.
2019-06-13 | GSE132637 | GEO
Project description:Multiple infection sources for enterohemorrhagic Escherichia coli O157:H7 are known, including food of animal origin and produce. The ecology of this pathogen outside its human host is largely unknown. One third of its annotated genes still are hypothetical. To identify genetic determinants expressed under environmental factors, we applied strand-specific RNA-sequencing of strain E. coli EDL933 under 11 different biotic and abiotic conditions: LB medium at pH4, pH7, pH9, or at 15°C; LB with nitrite or trimethoprim-sulfamethoxazole; LB-agar surface, M9 minimal medium, spinach leaf juice, surface of living radish sprouts, and cattle feces. Of 5379 annotated genes, only 144 are transcriptionally completely inactive under all conditions. Of 1,771 hypothetical genes, 1,672 exhibit significant transcriptional signals under at least one condition. The pathogenicity island LEE showed highest transcriptional activity in LB medium, minimal medium, and after treatment with antibiotics. Unique sets of genes, including many hypothetical genes, are highly up regulated on radish sprouts, cattle feces, or in the presence of antibiotics. For instance, azoR is biotechnologically important, but its environmental function has been elusive. This gene is highly active on radish sprouts. Further, we observed induction of the shiga-toxin carrying phages by antibiotics and confirmed active biofilm related genes on radish sprouts, in cattle feces, and on agar plates. Thus, environmental transcriptomics uncovers hitherto unknown gene functions and regulatory patterns of Escherichia coli O157:H7.
2014-07-20 | GSE48199 | GEO
Project description:Multiple infection sources for enterohemorrhagic Escherichia coli O157:H7 are known, including food of animal origin and produce. The ecology of this pathogen outside its human host is largely unknown. One third of its annotated genes still are hypothetical. To identify genetic determinants expressed under environmental factors, we applied strand-specific RNA-sequencing of strain E. coli EDL933 under 11 different biotic and abiotic conditions: LB medium at pH4, pH7, pH9, or at 15°C; LB with nitrite or trimethoprim-sulfamethoxazole; LB-agar surface, M9 minimal medium, spinach leaf juice, surface of living radish sprouts, and cattle feces. Of 5379 annotated genes, only 144 are transcriptionally completely inactive under all conditions. Of 1,771 hypothetical genes, 1,672 exhibit significant transcriptional signals under at least one condition. The pathogenicity island LEE showed highest transcriptional activity in LB medium, minimal medium, and after treatment with antibiotics. Unique sets of genes, including many hypothetical genes, are highly up regulated on radish sprouts, cattle feces, or in the presence of antibiotics. For instance, azoR is biotechnologically important, but its environmental function has been elusive. This gene is highly active on radish sprouts. Further, we observed induction of the shiga-toxin carrying phages by antibiotics and confirmed active biofilm related genes on radish sprouts, in cattle feces, and on agar plates. Thus, environmental transcriptomics uncovers hitherto unknown gene functions and regulatory patterns of Escherichia coli O157:H7. Eleven different conditions were sequenced on the SOLiD system. Of two of the condtions, spinach medium and LB-nitrite, technical replicates were sequenced. Of LB medium and radish sprouts, biological replicates were sequenced on an Illumina MiSeq.
2014-07-20 | E-GEOD-48199 | biostudies-arrayexpress
Project description:The emergence of polymyxin resistance in carbapenem-resistant and extended-spectrum -lactamase (ESBL)-producing bacteria is a critical threat to human health, and new treatment strategies are urgently required. Here, we investigated the ability of the safe-for-human use ionophore PBT2 to restore antibiotic sensitivity in polymyxin-resistant, ESBL-producing, carbapenem-resistant Gram-negative human pathogens. PBT2 was observed to resensitize Klebsiella pneumoniae, Escherichia coli, Acinetobacter baumannii and Pseudomonas aeruginosa to last-resort polymyxin class antibiotics, including the less-toxic next-generation polymyxin derivative, FADDI-287. We were unable to select for mutants resistant to PBT2 + FADDI-287 in polymyxin resistant E. coli containing a plasmid-borne mcr-1 gene or K. pneumoniae carrying a chromosomal mgrB mutation. Using a highly invasive K. pneumoniae strain engineered for polymyxin resistance through mgrB mutation, we successfully demonstrated the efficacy of PBT2 + FADDI-287 in vivo for the treatment of Gram-negative sepsis. These data present a new treatment modality to break antibiotic resistance in high priority polymyxin-resistant Gram-negative pathogens.
2020-07-01 | GSE153553 | GEO
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