Enterobacterales strain:Escherichia coli
Ontology highlight
ABSTRACT:
PROVIDER: PRJDB17717 | ENA |
REPOSITORIES: ENA
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Project description:Colistin is a crucial last-line drug used for the treatment of life-threatening infections caused by multi-drug resistant strains of the Gram-negative bacteria, Acinetobacter baumannii. However, colistin resistant A. baumannii isolates can be isolated following failed colistin therapy. Resistance is most often mediated by the addition of phosphoethanolamine (pEtN) to lipid A by PmrC, following missense mutations in the pmrCAB operon encoding PmrC and the two-component signal transduction system PmrA/PmrB. We recovered an isogenic pair of A. baumannii isolates from a single patient before (6009-1) and after (6009-2) failed colistin treatment that displayed low/intermediate and high levels of colistin resistance, respectively. To understand how increased colistin-resistance arose, we genome sequenced each isolate which revealed that 6009-2 had an extra copy of the insertion sequence element ISAba125 within a gene encoding an H-NS-family transcriptional regulator. Consequently, transcriptomic analysis of the clinical isolates identified was performed and more than 150 genes as differentially expressed in the colistin-resistant, hns mutant, 6009-2. Importantly, the expression of eptA, encoding a second lipid A-specific pEtN transferase, but not pmrC, was significantly increased in the hns mutant. This is the first time an H-NS-family transcriptional regulator has been associated with a pEtN transferase and colistin resistance.
2018-02-19 | GSE107964 | GEO
Project description:There is an urgent need for novel antibiotics against carbapenem and 3rd generation cephalosporin-resistant Gram-negative pathogens, for which the last-resort antibiotics have lost most of their efficacy. We describe here a novel class of synthetic antibiotics that was inspired from natural product-derived scaffolds. The antibiotics have an unprecedented mechanism of action, which targets the main component (BamA) of the Bam folding machinery required for folding and insertion of ß-barrel proteins into the outer membrane of Gram-negative bacteria. This OMPTA (outer membrane protein-targeting antibiotic) class shows potent activity against multidrug-resistant Gram-negative ESKAPE pathogens and overcomes colistin-resistance both in vitro and in vivo. A clinical candidate has the potential to address life threatening Gram-negative infections with high unmet medical need.
2019-10-22 | PXD010174 | Pride
Project description:There is an urgent need for novel antibiotics against carbapenem and 3rd generation cephalosporin-resistant Gram-negative pathogens, for which the last-resort antibiotics have lost most of their efficacy. We describe here a novel class of synthetic antibiotics that was inspired from natural product-derived scaffolds. The antibiotics have an unprecedented mechanism of action, which targets the main component (BamA) of the Bam folding machinery required for folding and insertion of ß-barrel proteins into the outer membrane of Gram-negative bacteria. This OMPTA (outer membrane protein-targeting antibiotic) class shows potent activity against multidrug-resistant Gram-negative ESKAPE pathogens and overcomes colistin-resistance both in vitro and in vivo. A clinical candidate has the potential to address life threatening Gram-negative infections with high unmet medical need.
2020-02-04 | MSV000084899 | MassIVE
Project description:To explore how multiple drug-resistant A. baumannii response to colistin resistance, we compared the genomic, transcriptional and proteomic profile of A. baumannii MDR-ZJ06 to that of induced colistin resistant strain ZJ06-200P5-1.
2017-03-15 | PXD005265 | Pride
Project description:Drug resistance and tolerance eliminate the therapeutic potential of antibiotics against pathogens. Antibiotic tolerance by bacterial biofilms often leads to persistent infections, but its mechanisms are unclear. To uncover antibiotic tolerance mechanisms in biofilms, we applied stable isotope labeling with amino acids (SILAC) proteomics to selectively label and compare proteomes of sensitive and tolerant subpopulations of biofilms formed by Pseudomonas aeruginosa towards colistin, a 'last-resort' antibiotic against multidrug-resistant Gram-negative pathogens. Migration was essential in forming colistin-tolerant biofilm subpopulations, as colistin-tolerant cell-aggregates migrated with type IV pili, onto the top of killed biofilm. The colistin-tolerant cell-aggregates employed quorum sensing (QS) to initiate the formation of fresh colistin-tolerant subpopulations, highlighting multicellular behavior in antibiotic tolerance development. Erythromycin treatment which inhibits motility and QS, boosted biofilm eradication by colistin. This novel ‘-omics’ strategy to study antibiotic tolerant cells provides key insights for designing novel treatments against infections unsuppressed by conventional antimicrobials.
2016-02-16 | PXD002369 | Pride
Project description:Polymyxins are increasingly used as the critical last-resort therapeutic options for multidrug-resistant gram-negative bacteria. Unfortunately, polymyxin resistance has increased gradually for the last few years. Although studies on mechanisms of polymyxin are expanding, system-wide analyses of the underlying mechanism for polymyxin resistance and stress response are still lacking. To understand how Klebsiella pneumoniae adapt to colistin (polymyxin E) pressure, we carried out proteomic analysis of Klebsiella pneumoniae strain cultured with different concentrations of colistin. Our results showed that the proteomic responses to colistin treatment in Klebsiella pneumoniae involving several pathways, including (i) gluconeogenesis and TCA cycle; (ii) arginine biosynthesis; (iii) porphyrin and chlorophyll metabolism; and (iv) enterobactin biosynthesis. Interestingly, decreased abundance of class A β-lactamases including TEM, SHV-11, SHV-4 were observed in cells treated with colistin. Moreover, we also present comprehensive proteome atlases of paired polymyxin-susceptible and -resistant Klebsiella pneumoniae strains. The polymyxin-resistant strain Ci, a mutant of Klebsiella pneumoniae ATCC BAA 2146, showed missense mutation in crrB. The crrB mutant Ci, which displayed lipid A modification with 4-amino-4-deoxy-L-arabinose (L-Ara4N) and palmitoylation, showed striking increases of CrrAB, PmrAB, PhoPQ, ArnBCADT and PagP. We hypothesize that crrB mutations induce elevated expression of the arnBCADTEF operon and pagP via PmrAB and PhoPQ. Moreover, multidrug efflux pump KexD, which was induced by crrB mutation, also contributed to colistin resistance. Overall, our results demonstrated proteomic responses to colistin treatment and the mechanism of CrrB-mediate colistin resistance, which may further offer valuable information to manage polymyxin resistance.
2022-04-11 | PXD018528 | Pride
Project description:Colistin resistance in Enterobacterales
| PRJEB47075 | ENA
Project description:Use of MePS2-modified siRNAs to target GRAM Domain Containing 1B (GRAMD1B), a novel protein in taxane resistance. Two groups of samples are included: 1. siControl treated HeyA8-MDR and 2. siGRAMD1B treated HeyA8-MDR. Gene expression profiles of siGRAMD1B-HeyA8-MDR cells were compared to that of siControl-HeyA8MDR cells.
2014-03-10 | E-GEOD-54459 | biostudies-arrayexpress