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ABSTRACT: Colistin-resistant Gram-negative bacteria isolated from the hospital water environment

PROVIDER: PRJNA756469 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15534433_1.fastq.gz	Fastqsanger.gz
	SRR15534433_2.fastq.gz	Fastqsanger.gz
	SRR15534434_1.fastq.gz	Fastqsanger.gz
	SRR15534434_2.fastq.gz	Fastqsanger.gz
	SRR15534435_1.fastq.gz	Fastqsanger.gz

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Colistin-resistant Gram-negative bacteria

Project description:Colistin-resistant Gram-negative bacteria isolated from the water environment of high-risk hospital units. Raw sequence reads

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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:Colistin-Resistant Gram-negative Bacteria Recovered from the Clinical Setting

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An Outer Membrane Protein-Targeting Antibiotic Against Resistant Gram-Negative Bacterial Pathogens

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

An Outer Membrane Protein-Targeting Antibiotic Against Resistant Gram-Negative Bacterial Pathogens

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Differential gene expression in mouse kidney following 72 hours of colistin exposure by Illumina WG-6_V2 array

Project description:Colistin sulfate (polymixin E) is an antibiotic prescribed with resurging frequency for multidrug resistant gram negative bacterial infections. It is associated with nephrotoxicity in humans in up to 33% of cases. Little is known regarding genes involved in colistin nephrotoxicity. A murine model of colistin-mediated kidney injury was developed. C57/BL6 mice were administered saline or colistin at a dose of 16mg/kg/day in 2 divided doses. An Illumina gene expression array was performed on kidney RNA harvested 72 hours after first colistin dose to identify differentially expressed genes early in drug treatment. Array platform was MouseWG-6, 48,000 probes. Drug given intraperitoneal. Total RNA was isolated from mouse kidneys which were harvested upon sacrifice. 12 total 10 week old C57 bl6 mice were analyzed. Six mice were administered 0.1% saline twice daily, six mice were given colistin at 16 mg/kg/day in 2 divided doses. The 2 groups were randomized to 2 different MouseWG-6_V2_0_R2_11278593 and groups were compared.

2013-11-05 | E-GEOD-46410 | biostudies-arrayexpress

Differential gene expression in mouse kidney following 72 hours of colistin exposure by Illumina WG-6_V2 array

2013-11-05 | GSE46410 | GEO

Project description:Multidrug-resistant Gram-negative bacteria

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Molecular Epidemiology of Enterobacterales Resistant to Antibiotics of Last Resort in Pregnant Women in Labour at a Tertiary Hospital

Project description:This study aims to determine the epidemiology of Enterobacteriaceae resistant to antibiotics of last resort in pregnant women in labour at a tertiary hospital, Pretoria, South Africa. Rectal swabs shall be used to screen for colonisation with CRE and colistin-resistant Enterobacteriales in pregnant women during labour. Carbapenem and colistin-resistant Enterobacterales can cause the following infections: bacteraemia; nosocomial pneumonia; urinary tract infections, and intra-abdominal infections. Due to limited treatment options, infections caused by these multidrug-resistant organisms are associated with a mortality rate of 40-50%. Screening for colonisation of carbapenem-resistant Enterobacteriaceae (CRE) and colistin-resistant Enterobacteriaceae will help implement infection and prevention measures to limit the spread of these multidrug-resistant organisms.

2022-07-20 | GSE208573 | GEO

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