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RNAseq transcriptome analysis of A. baumannnii MS14413 treated with PBT2, zinc and tetracycline

ABSTRACT: Acinetobacter baumannii causes high mortality in ventilator-associated pneumonia patients and antibiotic treatment is compromised in multi-drug resistant strains resistant to beta-lactams, carbapenems, cephalosporins, polymyxins and tetracyclines. Among COVID-19 patients receiving ventilator support, multi-drug resistant A. baumannii secondary infection is associated with a two-fold increase in mortality. Here we investigated the use of the 8-hydroxyquinoline ionophore PBT2 to break resistance of A. baumannii to tetracycline class antibiotics.

ORGANISM(S): Acinetobacter baumannii

PROVIDER: GSE175535 | GEO | 2021/12/17

REPOSITORIES: GEO

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The transcriptomic response of Acinetobacter baumannii to colistin and doripenem alone and in combination in an in vitro pharmacokinetics/pharmacodynamics model

Project description:Objectives: Colistin remains a last-line treatment for multidrug-resistant Acinetobacter baumannii and combined use of colistin and carbapenems has shown synergistic effects against multidrug-resistant strains. In order to understand the bacterial responses to these antibiotics we analysed the transcriptome of A. baumannii following exposure to each.

2014-11-30 | GSE62794 | GEO

RNAseq transcriptome analysis of K. pneumoniae MS6671 and E. coli MS8345 treated with PBT2

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

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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.

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2016-12-22 | PXD004236 | Pride

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2023-09-01 | E-MTAB-13272 | biostudies-arrayexpress

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