Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

AB569, A Nontoxic Chemical Tandem That Kills Major Human Pathogenic Bacteria

ABSTRACT: Antibiotic-resistant “super-bug” bacteria represent a global health problem with no imminent solutions. Here, we demonstrate that AB569 (acidified nitrite (A-NO2-) and Na2-EDTA) killed all Gram-negative and Gram-positive bacteria tested. AB569 was also efficacious at killing the model organism P. aeruginosa in biofilms and in a murine chronic lung infection model. AB569 was not toxic to human cell lines at bactericidal concentrations. RNA-Seq analyses upon treatment of P. aeruginosa with AB569 revealed a catastrophic loss of the ability to support core pathways encompassing DNA, RNA, protein, ATP biosynthesis, and iron metabolism. Electrochemical analyses elucidated that AB569 produced more stable SNO-proteins, potentially explaining one mechanism of bacterial killing. Our data implicate that AB569 is a safe and effective means to kill pathogenic bacteria, suggesting that simple strategies could be applied with highly advantageous therapeutic/toxicity index ratios to pathogens associated with a myriad of peri-epithelial infections and related disease scenarios.

ORGANISM(S): Pseudomonas aeruginosa PAO1

PROVIDER: GSE142611 | GEO | 2020/02/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

The natural product elegaphenone potentiates antibiotic effects against Pseudomonas aeruginosa

Project description:Natural products represent a rich source for antibiotics addressing versatile cellular targets. The deconvolution of their targets via chemical proteomics is often challenged by the introduction of large photocrosslinkers. Here we select elegaphenone, a largely uncharacterized natural product antibiotic bearing a native benzophenone core scaffold, for affinity-based protein profiling (AfBPP) in Gram-positive and Gram-negative bacteria. This study utilizes the alkynylated natural product scaffold as a probe to uncover intriguing biological interactions with the transcriptional regulator AlgP. Furthermore, proteome profiling of a Pseudomonas aeruginosa AlgP transposon mutant revealed unique insights into the mode of action. Elegaphenone enhanced the killing of intracellular P. aeruginosa in macrophages exposed to sub-inhibitory concentrations of the fluoroquinolone antibiotic norfloxacin.

2021-09-08 | PXD010476 | Pride

The anti-sigma factor MucA of Pseudomonas aeruginosa: dramatic differences of mucA22 vs. DmucA mutants in anaerobic acidified nitrite sensitivity of planktonic and biofilm bacteria in vitro and during chronic murine lung infection

Project description:In this study, the A-NO2- sensitivity of mucA22 mutant bacteria vs. a genome sequence-confirmed mucA deletion (∆mucA) mutant was determined. The ∆mucA is surprisingly more resistant to A-NO2- than mucA22 bacteria. The genes responsible for the disposal of nitric oxide (NO), a by-product of A-NO2-, were found to be near wild-type levels in the ∆mucA mutant yet were dramatically reduced in the mucA22 mutant.

2019-03-14 | GSE128220 | GEO

Do Copper enhance antibiotic resistance (AR) in resistant bacteria and/or induce AR in sensitive bacteria? [RNA-seq]

Project description:The aim of this experiment was to determine if the development of resistance to antibiotics can be driven by the concentration and speciation of Cu. Experimental setup was designed to investigate two hypotheses for which two strains of Gram- bacteria have been selected: - Do TE enhance AR in resistant bacteria? Resistant strain: Bioluminescent Pseudomonas aeruginosa PAO1 (Xen41, Tetracycline resistant) - Do TE induce AR in sensitive bacteria? Sensitive strain: Pseudomonas aeruginosa PAO1 (Wild Type)

2020-10-28 | GSE160187 | GEO

Do Copper enhance antibiotic resistance (AR) in resistant bacteria and/or induce AR in sensitive bacteria? [DNA-seq]

2020-10-28 | GSE160188 | GEO

Activation of immune pathways in common bed bugs, Cimex lectularius, in response to bacterial immune challenges - a transcriptomics analysis

Project description:The common bed bug, Cimex lectularius, is an urban pest of global health significance, severely affecting the physical and mental health of humans. In contrast to most other blood-feeding arthropods, bed bugs are not major vectors of pathogens, but the underlying mechanisms for this phenomenon are largely unexplored. Here, we present the first transcriptomics study of bed bugs in response to immune challenges. To study transcriptional variations in bed begs following ingestion of bacteria, we extracted and processed mRNA from immune-related tissues of adult male bed bugs after ingestion of sterile blood or blood laced with the Gram-positive (Gr+) bacterium Bacillus subtilis or the Gram-negative (Gr–) bacterium Escherichia coli. We analyzed mRNA from the bed bugs’ midgut (the primary tissue involved in blood ingestion) and from the rest of their bodies (RoB; body minus head and midgut tissues).

2024-03-18 | GSE256026 | GEO

Identification of constitutively-expressed immune effectors in the house fly (Musca domestica) and the transcription factors that regulate them

Project description:In this study we fed groups of female house flies one of two Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli) or control broth and used RNA-seq to determine differential gene expression at 4 hours post-feeding. Flies that ingested P. aeruginosa induced expression of genes encoding digestive proteins in the gut but did not induce AMPs. Flies in all treatment groups constitutively expressed some paralogs of lysozyme and AMP genes at the transcript level.

2024-07-22 | GSE182611 | GEO

Dual effect: High NADH levels contribute to efflux-mediated antibiotic resistance but drive ROS lethality

Project description:In light of the antibiotic crisis, emerging strategies to sensitize bacteria to available antibiotics should be explored. Several studies on the mechanisms of killing suggest that bactericidal antibiotic activity is enforced through the generation of reactive oxygen species (ROS lethality hypothesis). Here, we artificially manipulated the redox homeostasis of the model opportunistic pathogen Pseudomonas aeruginosa using specific enzymes that catalyze either the formation or oxidation of NADH. Increased NADH levels led to the activation of antibiotic efflux pumps and high levels of antibiotic resistance. However, higher NADH levels also resulted in increased intracellular ROS and amplified antibiotic killing. Our results demonstrate that growth inhibition and killing activity are mediated via different mechanisms. Furthermore, the profound changes in bioenergetics produced low virulence phenotypes characterized by reduced inter-bacterial signaling controlled pathogenicity traits. Our results pave the way for a more effective infection resolution and add an anti-virulence strategy to maximize chances to combat devastating P. aeruginosa infections while reducing the overall use of antibiotics.

2021-11-17 | GSE188801 | GEO

Galectin-3 Marks Protection from Lethal Bacterial Infection in Mice and Acute Respiratory Failure in Humans

Project description:Infection by the Gram-negative bacterium Pseudomonas aeruginosa is common in hospitalized immunocompromised as well as immunocompetent ventilated patients and is often life-threatening because of resistance of the bacteria to antibiotics. This prompts the question whether the host’s immune system can be educated to combat this bacterium. Bacterial lipopolysaccharide (LPS) is known to promote host resistance to bacterial infections although an understanding of the underlying mechanism is lacking. Here we show that prior exposure to a single low dose of LPS protects mice from a lethal infection by P. aeruginosa. These mice displayed expansion of a neutrophil and an interstitial macrophage population that were barely detectable in mice that did not receive LPS prior to infection. Both cell populations were distinguishable from other immune cell populations by being enriched in gene sets that included phagocytosis- and cell-killing-associated genes. The cell killing gene set in the neutrophil population uniquely expressed Lgals3, which encodes the multifunctional antibacterial protein, galectin-3. Intravital imaging of neutrophils for bacterial phagocytosis, assessment of bacterial killing and neutrophil-associated galectin-3 protein levels together with use of galectin-3-deficient mice collectively highlight neutrophils and galectin-3 as central players in LPS-mediated protection. Interrogating the relevance of these findings in hospitalized patients with acute respiratory failure revealed significantly higher galectin-3 levels in endotracheal aspirates (ETAs) of survivors compared to non-survivors, galectin-3 levels strongly correlating with a neutrophil signature in the ETAs. Taken together, our study provides impetus to harnessing the potential of galectin-3-expressing neutrophils to protect the lung from lethal infections and respiratory failure.

2024-04-15 | GSE237646 | GEO

Characterization of five novel Pseudomonas aeruginosa cell-surface signaling systems

Project description:Cell-surface signaling is a sophisticated regulatory mechanism used by gram-negative bacteria to sense signals from outside the cell and transmit them into the cytoplasm. This regulatory system consists of an outer membrane-localized TonB-dependent receptor (TonB-dependent transducer), a cytoplasmic membrane-localized anti-sigma factor and an extracytoplasmic function (ECF) sigma factor. By microarray analysis we have identified the regulons of four novel P. aeruginosa signaling systems. For that, the ECF sigmas PA0149, PA2050, PA2093 and PA4896 have been overexpressed in P. aeruginosa and their target gene candidates have been identified using DNA microarray. Keywords: Overexpression of ECF sigma factors

2007-11-24 | GSE9657 | GEO

Antibacterial activities of the algal bromophenol methylrhodomelol against Pseudomonas aeruginosa

Project description:Methylrhodomelol (1) is a bromophenol from the red alga Vertebrata lanosa (L.) T.A.Christensen that has been associated with antimicrobial properties. Aim of the current study was therefore, to assess the antimicrobial potential of this compound in more detail against the gram-negative pathogen Pseudomonas aeruginosa. 1 exerted weak bacteriostatic activity against different strains when grown in minimal medium, whereas other phenolics were inactive. In addition, 1 (35 and 10 µg/mL) markedly enhanced the susceptibility of multidrug resistant P. aeruginosa towards the aminoglycoside gentamicin, while it did not affect the viability of Vero kidney cells up to 100 µM. Finally, pyoverdine release was reduced in bacteria treated at sub-inhibitory concentration, but no effect on other virulence factors was observed. Transcriptome analysis of treated versus untreated P. aeruginosa indicated an interference of 1 with bacterial carbon and energy metabolism, which was corroborated by RT-qPCR and decreased ATP-levels in treated bacteria.

2024-04-07 | GSE249483 | 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