Brominated carbazole's antibiotic adjuvant effects in MRSA 43300
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA796022 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR17535772_1.fastq.gz | Fastqsanger.gz | |||
| SRR17535772_2.fastq.gz | Fastqsanger.gz | |||
| SRR17535773_1.fastq.gz | Fastqsanger.gz | |||
| SRR17535773_2.fastq.gz | Fastqsanger.gz | |||
| SRR17535774_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is a major threat to human health. Rather than depend on creating new antibiotics (to which bacteria will eventually become resistant), we are employing antibiotic adjuvants that potentiate existing antibiotics. Based on our previous work, loratadine, the FDA-approvide antihistamine, effectively potentiates cell-wall active antibiotics in multiple strains of MRSA. Furthermore, loratadine and oxacillin helped disrupt preformed biofilms and stop them from initially forming in vitro. To gain biological insight into how this potentiation and biofilm inhibition occurs, we used RNA-seq on treated MRSA 43300 cultures to examine antibiotic adjuvant affects transcritome-wide.
2023-03-23 | GSE227099 | GEO
Project description:Loratadine's antibiotic adjuvant effects in MRSA 43300
| PRJNA943228 | ENA
Project description:Methicillin-resistant Staphylococcus aureus (MRSA) is a major threat to human health, as the US mortality rate outweighs those from HIV, tuberculosis, and viral hepatitis combined. In the wake of the COVID-19 pandemic, antibiotic resistant bacterial infections acquired during hospital stays have increased. Instead of designing and deploying new antibiotics which MRSA would quickly develop resistance to, adjuvants are a key strategy to combatting these bacteria. We have evaluated several small molecule adjuvants that have strong potentiation with β-lactam antibiotics and have now investigated at the molecular level how the lead adjuvant exerts its effects. We hypothesized that the expression levels of key resistance genes would decrease once cotreated with a β-lactam antibiotic (oxacillin) and the adjuvant (compound 8). Furthermore, bioinformatic analyses would reveal biochemical pathways enriched in differentially expressed genes. RNA-seq analysis showed 176 and 233 genes significantly up and downregulated, respectively, upon cotreatment with oxacillin and compound 8. We identified four subclusters of genes that were regulated in similar patterns in response to drug treatment. Many of these genes displayed a similar pattern of expression where they were unaffected by compound 8 treatment alone, upregulated upon antibiotic challenge, and downregulated again upon cotreatment. GO categories that were significantly enriched among downregulated genes involved carbohydrate utilization and/or transport. Most of the biochemical pathways enriched with significantly downregulated genes involved carbohydrate utilization, such as the citric acid cycle (p=6.4x10-6) and the phosphotransferase system (p=1.8x10-5). The most populated pathway was S. aureus infection (p=3.0x10-3). Creating a network of affected gene products helped uncover potential master regulators for further investigation. This study revealed a dramatic impact of our lead adjuvant on the transcriptome that is consistent with a pleiotropic effect. These results point to this adjuvant as having potential broad therapeutic use in combatting MRSA infections.
2022-04-14 | GSE193395 | GEO
Project description:Hemolysins are lytic exotoxins expressed in most strains of S. aureus, but hemolytic activity varies between strains. We have previously reported several novel anti-virulence compounds that disrupt the S. aureus transcriptome, including hemolysin gene expression. This report delves further into our two lead compounds, loratadine and a structurally related brominated carbazole, and their effects on hemolysin production in methicillin-resistant S. aureus (MRSA). To gain understanding into how these compounds affect hemolysis, we analyzed these exotoxins at the DNA, RNA, and protein level after in vitro treatment. While lysis of red blood cells varied between strains, DNA sequence variation did not account for it. We hypothesized that our compounds would modulate gene expression of multiple hemolysins in two hospital-acquired strains of MRSA, both with staphylococcal cassette chromosome mec (SCCmec) type II. RNA-seq analysis of differential gene expression in untreated and compound-treated cultures revealed hundreds of differentially expressed genes, with a significant enrichment in genes involved in hemolysis. The brominated carbazole and loratadine both displayed the ability to reduce hemolysis in strain 43300 but displayed differential activity in strain USA100. These results corroborate gene expression studies as well as western blots of alpha hemolysin. Together, this work suggests that small molecules may alter exotoxin production in MRSA but that the directionality and/or magnitude of the difference are likely strain dependent.
2024-05-15 | GSE267020 | GEO
Project description:Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is life-threatening and occurs in up to 30% of MRSA bacteremia cases despite appropriate antimicrobial therapy. Isolates of MRSA that cause antibiotic-persistent MRSA bacteremia (APMB) typically have in vitro antibiotic susceptibilities equivalent to those causing antibiotic-resolving MRSA bacteremia (ARMB). Thus, persistence reflects host-pathogen interactions occurring uniquely in context of antibiotic therapy in vivo. However, host factors and mechanisms involved in APMB remain unclear. We compared DNA methylomes in circulating immune cells from patients experiencing APMB vs. ARMB. Overall, methylation signatures diverged in the distinct patient cohorts. Differentially methylated sites intensified proximate to transcription factor binding sites, primarily in enhancer regions. In APMB patients, significant hypo-methylation was observed in binding sites for CCAAT enhancer binding protein (C/EBP) and signal transducer / activator of transcription 1 (STAT1). In contrast, hypo-methylation in ARMB patients localized to glucocorticoid receptor and histone acetyltransferase p300 binding sites. These distinct methylation signatures were enriched in neutrophils and achieved a mean area under the curve of 0.85 when used to predict APMB using a classification model. These findings differentiate epigenotypes in patients experiencing APMB vs. ARMB, and suggest a risk stratification strategy for antibiotic persistence in patients treated for MRSA bacteremia.
2021-03-01 | GSE150144 | GEO
Project description:A leading cause of morbidity and mortality during influenza infection is the development of a secondary bacterial pneumonia, which is appropriately treated with antibiotics. In the absence of a bacterial superinfection, prescribing antibiotics is not indicated but has nevertheless become a common clinical practice for those presenting with a respiratory viral illness. We found that antibiotic use during an antecedent influenza infection impaired the lung innate immunologic defenses toward a secondary challenge with methicillin-resistantStaphylococcus aureus(MRSA). The antibiotics perturbed the gut microbiome causing a fungal dysbiosis that drives an increase in lung eosinophils. We also demonstrate eosinophils, through the release of major basic protein, impair macrophage ability to clear MRSA. Moreover, we provide clinical evidence that eosinophils positively correlate with antibiotic use and worsened outcomes in patients hospitalized for viral infections. Altogether, our work establishes a counterproductive effect of antibiotic treatment during influenza infection that have negative immunologic consequences in the lungs thereby increasing the risk of developing a secondary bacterial infection.
2024-08-21 | GSE243542 | GEO
Project description:The success of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) as pathogens is due to a combination of antibiotic resistance with high virulence. However, evolution of the exceptional virulence potential of CA-MRSA is not understood. Our previous study indicated that differential gene expression contributes substantially to this process. Thus, we here investigated the role of the pivotal virulence gene regulatory system agr in the most prevalent CA-MRSA strain USA300. Using a mouse subcutaneous infection model, we show that agr is essential for the development of CA-MRSA skin infections, the most frequent manifestation of disease caused by CA-MRSA. Furthermore, genome-wide analysis of gene expression revealed significant differences in agr-dependent virulence gene regulation between CA-MRSA, HA-MRSA, and laboratory strains. Our findings demonstrate that agr functionality is critical for CA-MRSA disease and indicate that an adaptation of the agr regulon to optimize expression of a broad set of virulence determinants may have contributed to the evolution of exceptionally pronounced virulence of CA-MRSA strains. Keywords: wild type vs mutant
2011-03-29 | GSE18793 | GEO
Project description:Micronanoparticled risedronate exhibits potent vaccine adjuvant effects
| PRJNA1000475 | ENA
Project description:The success of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) as pathogens is due to a combination of antibiotic resistance with high virulence. However, evolution of the exceptional virulence potential of CA-MRSA is not understood. Our previous study indicated that differential gene expression contributes substantially to this process. Thus, we here investigated the role of the pivotal virulence gene regulatory system agr in the most prevalent CA-MRSA strain USA300. Using a mouse subcutaneous infection model, we show that agr is essential for the development of CA-MRSA skin infections, the most frequent manifestation of disease caused by CA-MRSA. Furthermore, genome-wide analysis of gene expression revealed significant differences in agr-dependent virulence gene regulation between CA-MRSA, HA-MRSA, and laboratory strains. Our findings demonstrate that agr functionality is critical for CA-MRSA disease and indicate that an adaptation of the agr regulon to optimize expression of a broad set of virulence determinants may have contributed to the evolution of exceptionally pronounced virulence of CA-MRSA strains. Keywords: wild type vs mutant Wild type vs mutant agr strains.
2011-03-29 | E-GEOD-18793 | biostudies-arrayexpress
Project description:S. aureus ATCC 25923 is performance standard for antimicrobial susceptibility testing. S. aureus ATCC 33591 showed resistance against erytrhromycin, penicillin, and streptomycin. We used microarray to compare RNA expression between sensitive and resistant strain of S. aureus as a preliminary research for MRSA inhibition.
2010-09-15 | GSE18289 | GEO