Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fosfomycin uptake in Escherichia coli is mediated by the outer membrane porins OmpF, OmpC and LamB

ABSTRACT: The antibiotic fosfomycin is widely recognized for treatment of lower urinary tract infections caused by Escherichia coli and lately gained importance as a therapeutic option to combat multidrug resistant bacteria. Still, resistance to fosfomycin frequently develops through mutations reducing its uptake. Whereas the inner membrane transport of fosfomycin has been extensively studied in E. coli, its outer membrane (OM) transport remains insufficiently understood. While evaluating minimal inhibitory concentrations in OM porin-deficient mutants, we observed that the E. coli ΔompCΔompF strain is five times more resistant to fosfomycin than the wild type and the respective single mutants. Continuous monitoring of cell lysis of porin-deficient strains in response to fosfomycin additionally indicated the relevance of LamB. Furthermore, the physiological relevance of OmpF, OmpC and LamB for fosfomycin uptake was confirmed by electrophysiological and transcriptional analysis. This study expands the knowledge of how fosfomycin crosses the OM of E. coli.

ORGANISM(S): Escherichia coli BW25113

PROVIDER: GSE236554 | GEO | 2024/01/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Fosfomycin uptake in Escherichia coli is mediated by the outer membrane porins OmpF, OmpC and LamB

Project description:Fosfomycin uptake in Escherichia coli is mediated by the outer membrane porins OmpF, OmpC and LamB

| PRJNA991559 | ENA

Porin-mediated passage of negamycin across the outer membrane of Escherichia coli

Project description:The rise of antimicrobial resistant pathogens calls for new antibacterial treatments, but potent new compounds are scarce. Development of new antibiotics is difficult, especially against Gram-negative bacteria, as here uptake is strongly hindered by the additional outer membrane. Most antimicrobial agents against Gram-negatives use the porin mediated pathway to cross the outer membrane, which limits the choice of an antibiotic, as it has to fit by size, charge and hydrophilicity. In E. coli, the major porins OmpF and OmpC are associated with antibiotic translocation and therefore also with unspecific antibiotic cross-resistance. In this regard, alternative uptake routes are of interest. We were interested in the uptake opportunities of the small, natural product antibiotic negamycin and thereby found new uptake pathways across the outer membrane of E. coli. Besides OmpF and OmpC, we investigated the role of the minor porins OmpN and ChiP in negamycin translocation. We detected an effect of OmpN and ChiP on negamycin susceptibility and confirmed passage by electrophysiological assays. The structure of OmpN was resolved in order to analyze the negamycin translocation mechanism by computational simulations. As abundancy of these minor porins was low in E. coli, their transcript levels were analyzed by RNA-Seq. Increased transcripts levels of ompN and chiP were observed upon negamycin treatment, hinting at a role in antibiotic uptake. These new, additional uptake pathways across the outer membrane of E. coli highlight the antibiotic potential of negamycin, especially as resistance development is low due to availability of multiple uptake routes at both the outer and inner membranes

2023-10-01 | GSE183363 | GEO

Staphylococcus aureus treated with fosfomycin

Project description:Staphylococcus aureus is a highly adaptable human pathogen; therefore a constant search for new effective antibiotic compounds is being preformed. Gene expression profiling can be used to determine potential targets and mechanisms of action (MOA) of known or potential drugs. The goal of our study was a development of a focused transcriptome platform to be used for confirming the MOA of new chemical entities which are designed as inhibitors of Mur ligases. A model transcriptional profile was set up for well described inhibitor of MurA ligase, fosfomycin. Moreover, we wanted to identify the pathways and processes primarily affected by this compound. S. aureus ATCC 29213 cells were treated with low concentrations of fosfomycin (1 and 4 Âµg/ml, respectively) and harvested at 10, 20 and 40 minutes after treatment, respectively. RNA was isolated, transcribed, labeled and hybridized to S. aureus GeneChips, representing approximately 3000 S. aureus genes. Using meta-analysis of our results and the results in the S. aureus microarray database, we have confirmed that fosfomycin induces âcell wall stimulonâ genes and were able to identify genes and pathways specifically modulated by fosfomycin. Time course, different fosfomycin concentration

2010-05-20 | E-GEOD-15394 | biostudies-arrayexpress

Staphylococcus aureus treated with fosfomycin

Project description:Staphylococcus aureus is a highly adaptable human pathogen; therefore a constant search for new effective antibiotic compounds is being preformed. Gene expression profiling can be used to determine potential targets and mechanisms of action (MOA) of known or potential drugs. The goal of our study was a development of a focused transcriptome platform to be used for confirming the MOA of new chemical entities which are designed as inhibitors of Mur ligases. A model transcriptional profile was set up for well described inhibitor of MurA ligase, fosfomycin. Moreover, we wanted to identify the pathways and processes primarily affected by this compound. S. aureus ATCC 29213 cells were treated with low concentrations of fosfomycin (1 and 4 µg/ml, respectively) and harvested at 10, 20 and 40 minutes after treatment, respectively. RNA was isolated, transcribed, labeled and hybridized to S. aureus GeneChips, representing approximately 3000 S. aureus genes. Using meta-analysis of our results and the results in the S. aureus microarray database, we have confirmed that fosfomycin induces “cell wall stimulon” genes and were able to identify genes and pathways specifically modulated by fosfomycin.

2009-03-26 | GSE15394 | GEO

Phenotypic convergent evolution towards fosfomycin collateral sensitivity of Pseudomonas aeruginosa antibiotic resistant mutants

Project description:In this work we describe a robust fosfomycin collateral sensitivity phenotype of Pseudomonas aeruginosa resistant mutants selected by antibiotics from different structural families. The underlying mechanism was the reduced expression of the genes encoding the peptidoglycan-recycling pathway, which preserves the peptidoglycan synthesis in situations where the de novo synthesis is blocked, and of fosA, encoding a fosfomycin-inactivating enzyme.

2022-03-02 | GSE153006 | GEO

Effects of fosfomycin on biofilm of a clinical Staphylococcus aureus isolated from osteoarticular infection by transcriptomal approach

Project description:The aim of the present study was to investigate the mechanisms by which fosfomycin restrains biofilm formation and affects a 24h-old biofilm of S. aureus. RNA sequencing (RNA-Seq) technology was used to compare the transcriptomes of S. aureus biofilms formed or treated with sublethal concentrations of fosfomycin.

2018-01-31 | GSE83269 | GEO

Fosfomycin and the intermediate metabolites PEP and GA-3P effect on Stenotrophomonas maltophilia transcriptome

Project description:Transcriptomic analysis of S. maltophilia D457 after one-hour induction with the antibiotic fosfomycin, the intermediate metabolites phosphoenolpyruvate or glyceraldehyde-3-phosphate

2022-01-19 | GSE181918 | GEO

Phenotypic and transcriptional analysis of the osmotic regulator OmpR in Yersinia pestis

Project description:Background The osmotic regulator OmpR in Escherichia coli regulates differentially the expression of major porin proteins OmpF and OmpC. In Yersinia enterocolitica and Y. pseudotuberculosis, OmpR is required for both virulence and survival within macrophages. However, the phenotypic and regulatory roles of OmpR in Y. pestis are not yet fully understood. Results Y. pestis OmpR is involved in building resistance against phagocytosis and controls the adaptation to various stressful conditions met in macrophages. The ompR mutation likely did not affect the virulence of Y. pestis strain 201 that was a human-avirulent enzootic strain. The microarray-based comparative transcriptome analysis disclosed a set of 224 genes whose expressions were affected by the ompR mutation, indicating the global regulatory role of OmpR in Y. pestis. Real-time RT-PCR or lacZ fusion reporter assay further validated 16 OmpR-dependent genes, for which OmpR consensus-like sequences were found within their upstream DNA regions. ompC, F, X, and R were up-regulated dramatically with the increase of medium osmolarity, which was mediated by OmpR occupying the target promoter regions in a tandem manner. Conclusion OmpR contributes to the resistance against phagocytosis or survival within macrophages, which is conserved in the pathogenic yersiniae. Y. pestis OmpR regulates ompC, F, X, and R directly through OmpR-promoter DNA association. There is an inducible expressions of the pore-forming proteins OmpF, C, and X at high osmolarity in Y. pestis, in contrast to the reciprocal regulation of them in E. coli. The main difference is that ompF expression is not repressed at high osmolarity in Y. pestis, which is likely due to the absence of a promoter-distal OmpR-binding site for ompF.

2011-10-24 | GSE26601 | GEO

Transcriptional response of P. aeruginosa to fosfomycin tobramycin and FT under aerobic and anaerobic conditions

Project description:The experiment aimed to characterise the transcriptional response of a clinical CF P. aeruginosa isolate to sub-inhibitory concentrations of fosfomycin, tobramycin and a novel 4/1 (w/w) combination of the two (FT) under both aerobic and anaerobic conditions

2013-08-28 | E-MEXP-3764 | biostudies-arrayexpress

Determinants of heat resistance in Escherichia coli AW1.7

Project description:Microarray hybridization of cDNA libraries obtained from exponentially growing or heat-shocked AW1.7 or GGG10 cultures was performed to compare gene expression of these two strains. Expression of selected genes from different functional groups was quantified by quantitative PCR (q-PCR). DnaK, 30S and 50S risobomal subunits were overexpressed in E. coli GGG10 relative to E. coli AW1.7 upon heat shock at 50°C, indicating improved ribosome stability. The outer membrane porin NmpC and several transport proteins were overexpressed in exponentially growing E. coli AW1.7.

2011-03-02 | GSE27607 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data