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Responses of Pseudomonas aeruginosa to last resort antibiotics

ABSTRACT: Responses of Pseudomonas aeruginosa to last resort antibiotics monitored by transcriptome and translatome analyses

PROVIDER: PRJEB41029 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	ERR4777164.fastq.gz	Fastqsanger.gz
	ERR4777165.fastq.gz	Fastqsanger.gz
	ERR4777166.fastq.gz	Fastqsanger.gz
	ERR4777167.fastq.gz	Fastqsanger.gz
	ERR4777168.fastq.gz	Fastqsanger.gz

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Pseudomonas aeruginosa antibiotics

Project description:Responses of Pseudomonas aeruginosa to last resort antibiotics monitored by transcriptome and translatome analyses

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Genome-scale metabolic modelling of responses to polymyxins in Pseudomonas aeruginosa

Project description:Background: Pseudomonas aeruginosa often causes multidrug-resistant infections in immunocompromised patients and polymyxins are often used as the last-line therapy. Alarmingly, resistance to polymyxins has been increasingly reported worldwide recently. To rescue this last-resort class of antibiotics, it is necessary to systematically understand how P. aeruginosa alters its metabolism in response to polymyxin treatment, thereby facilitating the development of effective therapies. To this end, a genome-scale metabolic model (GSMM) was employed to analyse bacterial metabolic changes at the systems level. Findings: A high-quality GSMM iPAO1 was constructed for P. aeruginosa PAO1 for antimicrobial pharmacological research. Model iPAO1 encompasses an additional periplasmic compartment and contains 3,022 metabolites, 4,265 reactions and 1,458 genes in total. Growth prediction on 190 carbon and 95 nitrogen sources achieved an accuracy of 89.1%, outperforming all reported P. aeruginosa models. Notably, prediction of the essential genes for growth achieved a high accuracy of 87.9%. Metabolic simulation showed that lipid A modifications associated with polymyxin resistance exert a limited impact on bacterial growth and metabolism, but remarkably change the physiochemical properties of the outer membrane. Modelling with transcriptomics constraints revealed a broad range of metabolic responses to polymyxin treatment, including reduced biomass synthesis, upregulated amino acids catabolism, induced flux through the tricarboxylic acid cycle, and increased redox turnover. Conclusions: Overall, iPAO1 represents the most comprehensive GSMM constructed to date for Pseudomonas. It provides a powerful systems pharmacology platform for the elucidation of complex killing mechanisms of antibiotics.

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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.

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Project description:Antibiotics in low concentrations may have an array of effects. We have exposed growing P. aeruginosa cells to different classes of antibiotics in order to investigate this hypothesis. We have used DNA microarrays to investigate the effect of low concentrations of antibiotics (azithromycin, ceftazidime and ciprofloxacin) on the gene expression of P. aeruginosa aiming to elucidate general trends. Keywords: Treatment with antibiotics

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Elucidation of the substrate specificity of the ABC transporter Tba uncovers an unsuspected role in the biosynthesis of glycopeptide antibiotics

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