Ontology highlight
ABSTRACT:
PROVIDER: PRJNA558684 | ENA |
REPOSITORIES: ENA
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Project description:Caerin 1 is a family of host-defense peptides with antimicrobial property originally isolated from Australia tree frog. Caerin 1.1+1.9 has been shown to inhibit multiple antibiotic resistant bacteria infection both in vitro and in vivo. In current study, we compare the MICs of caerin 1.1/1.9 with commonly used antibiotics against S. aureus, Copper-Green Pseudomonas aeruginosa, Acinetobacter baumannii, and Streptococcus haemolyticus. We demonstrate that caerin 1.1/1.9 not only prevent the formation of biofilm by A. Baumann, but also have therapeutic effect on established biofilm. In addition, we find that caerin1.1/1.9 significantly inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA) strain in a murine skin infection model. The quantitative proteomic analysis suggested that caerin1.1/1.9 largely activate oxidative phosphorylation, as well as several pathways associated with tissue repair and growth, with respect to the untreated tissues infected with MRSA in mice. In summary, our results suggest that caerin 1.1/1.9 have the potential to be used as a drug candidate treating complicated antibiotic resistant bacterial infection in human.
2023-10-11 | PXD044425 | Pride
Project description:Methicillin-resistant Staph. Aureus (MRSA) is a common cause of severe pneumonia and sepsis that can lead to Acute Respiratory Distress Syndrome (ARDS). MRSA causes lung endothelial cell (EC) dysfunction, a critical step in the pathogenesis and progression of lung injury. Our previous studies have demonstrated that FTY720 S-phosphonate (Tysiponate, Tys), an analog of sphingosine-1-phosphate, ameliorates MRSA-induced lung EC activation and barrier disruption (PMID: 35015568). To advance our mechanistic understanding of MRSA and Tys effects on lung EC, we investigated associated epigenetic changes. Specifically, we studied histone lysine acetylation, which is a central epigenetic alteration that has been linked to gene transcription and functional regulation of endothelial responses to inflammatory stimuli. We therefore determined the effects of MRSA exposure in the presence or absence of Tys on lung EC acetylation at the 9th lysine residue of the histone H3 protein (H3K9ac), which is an important chromatin modification associated with active promoters and gene activation. ChIP-seq analysis was employed to perform an unbiased genome-wide profiling of H3K9ac epigenetic patterns in human lung EC. This analysis identified multiple genes that are differentially targeted by acetylation when EC are exposed to MRSA±Tys.
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Project description:Previous studies have documented the diversity of genetic background of methicillin-resistant S. aureus (MRSA) strains associated with healthcare (HA-MRSA), community (CA-MRSA) and livestock (LA-MRSA). The accessory and core-variable genome content of those strains remain largely unknown. To compare the composition of accessory and core-variable genome of Belgian MRSA strains according to host, population setting and genetic background, representative strains of HA- (n=21), CA- (n = 13) and ST398 LA-MRSA (n = 18) were characterized by a DNA-microarray (StaphVar Array) composed of oligonucleotide probes targeting ~400 resistance, adhesion and virulence associated genes.ST398 strains displayed very homogenous hybridization profiles (>94% gene content homology) irrespective of their host origin. This “ST398-specific” genomic profile was not distantly demarked from those of certain human-associated lineages but lacked several virulence- and colonization-associated genes harbored by strains of human origin, such as genes encoding proteases, haemolysins or adhesins. No enterotoxin gene was found among ST398 strains. In conclusion, our findings are consistent with a non-human origin of this ST398 lineage but suggest that it might have the potential to adapt further to the human host.
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