Ontology highlight
ABSTRACT:
PROVIDER: PRJEB18727 | ENA |
REPOSITORIES: ENA
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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 potentiation 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. A structurally related brominated carbazole, compound 8, showed similar antibiotic potentiation. To gain biological insight into these transcriptome disruptors in a more clinically relevant strain of MRSA, we used RNA-seq on treated MRSA USA100 cultures.
2024-05-15 | GSE267020 | GEO
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:Methicillin-resistant Staphylococcus aureus (MRSA) remains a global health threat with an over 14% fatality rate, in case of invasive infection, in 2011. Multi-drug resistance is the main reason for the failure of therapy. Use of antimicrobial drug combinations with synergistic effect is increasingly seen as a critical strategy to combat multi-drug resistant pathogens such as MRSA. However, the mechanism of synergistic effect has yet been systematically studied. In this work, we investigated a new erythromycin derivative, SIPI-8294, which has been demonstrated to have synergistic effect with oxacillin against MRSA, unlike its parent compound erythromycin. To obtain insights into the mechanism for the synergistic effect, label-free quantitative proteomics was employed. Cultured MRSA was exposed to sub-inhibitory doses of oxacillin, SIPI-8294, erythromycin, and combinations of SIPI-8294/oxacillin and erythromycin/oxacillin to reveal the global proteome responses to drug treatment. Results showed that 200 proteins were differentially expressed in SIPI-8294/oxacillin-treated cells. Among these proteins, the expression levels of penicillin binding protein 2a and β-lactamase, two proteins mainly responsible for oxacillin resistance, were four times lower in the SIPI-8294/oxacillin treatment group than in the erythromycin/oxacillin treatment group. Quantitative real-time PCR analysis also revealed similar trends at the transcription level. These results suggest that the synergistic mechanism may be related to interference with the known oxacillin resistance mechanism. The data also provided some evidence that the combination of SIPI-8294 and oxacillin appears to impact oxidation-reduction homeostasis and cell wall biosynthesis.
2022-03-01 | PXD001494 | Pride
Project description:Panton-valentine leukocidin (PVL) has been linked to worldwide emergence of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) -- its role in virulence in unclear. Here we show that PVL had no effect on global gene expression of prominent CA-MRSA strains nor did it affect bacterial clearance from lungs, spleen and kidneys in a highly discriminatory rabbit bacteremia model. These findings negate a large body of epidemiological research that implicated PVL in CA-MRSA virulence. Keywords: mutant vs wild type in 2 different growth phases grown in 2 different medias
2008-09-12 | GSE8677 | GEO
Project description:To determine the role of the second gene in the vra operon (vraT) in the stress response to oxacillin, we compared the oxacillin induction profiles in a vraT deletion strain to that of a vraSR mutant in a USA300 MRSA strain background. Nonpolar deletion of vraT and insertional inactivation of vraS was constructed in MRSA strain USA300.
2012-11-30 | E-GEOD-39627 | biostudies-arrayexpress
Project description:Panton-valentine leukocidin (PVL) has been linked to worldwide emergence of community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) -- its role in virulence in unclear. Here we show that PVL had no effect on global gene expression of prominent CA-MRSA strains nor did it affect bacterial clearance from lungs, spleen and kidneys in a highly discriminatory rabbit bacteremia model. These findings negate a large body of epidemiological research that implicated PVL in CA-MRSA virulence. Keywords: mutant vs wild type in 2 different growth phases grown in 2 different medias Wild type USA 300 (strain SF8300), wild type USA 400 (strain MW2) were compared against their respective PVL isogenic knock out strains. Strains were compared at both mid-exponential and stationary phase and grown in both TSB and CCY to determine if PVL plays a role in gene regulation under these conditions.
2010-06-19 | E-GEOD-8677 | biostudies-arrayexpress
Project description:To determine the role of the second gene in the vra operon (vraT) in the stress response to oxacillin, we compared the oxacillin induction profiles in a vraT deletion strain to that of a vraSR mutant in a USA300 MRSA strain background.
2012-11-30 | GSE39627 | GEO
Project description:Staphylococcus aureus is a gram-positive cocci and an important human commensal bacteria and pathogen. S. aureus infections are increasingly difficult to treat because of the emergence of highly resistant MRSA (Methicillin-resistant S. aureus) strains. Here we present a method to study differential gene expression in S. aureus using high-throughput RNA-sequencing (RNA-seq). We use RNA-seq to examine the differential gene expression in S. aureus RN4220 cells containing an exogenously expressed transcription factor and between two S. aureus strains (RN4220 and NCTC8325-4). The information provided by RNA-seq was a significant advance over previously described microarray based techniques. We investigated the sequence and gene expression differences between RN4220 and NCTC8325-4 and used the RNA-seq data to identify S. aureus promoters suitable for in vitro analysis. We used RNA-seq to describe, on a genome wide scale, genes positively and negatively regulated by a phage encoded transcription factor, gp67. RNA-seq offers the ability to study differential gene expression with single-nucleotide resolution, and is a considerable improvement over the predominant genome-wide transcriptome technologies used in S. aureus. RNA-seq analysis of Staphylococcus aureus RN4220 (electrocompetent strain) carrying either empty pRMC2 (inducible expression vector) or pRMC2 carrying the ORF67 gene (encodes gp67). Both strains were grown to OD 0.2 and transgene expression was induced with 100ng/ml anhydrotetracycline. As a control, Staphylococcus aureus strain NCTC8325-4 (non-electrocompetent strain) was grown under identical conditions except without the addition of anhydrotetracycline.
2013-11-07 | E-GEOD-48896 | biostudies-arrayexpress
Project description:Staphylococcus aureus can cause serious skin, respiratory, and other life-threatening invasive infections in humans, and methicillin-resistant S. aureus (MRSA) strains have been acquiring increasing antibiotic resistance. While MRSA was once mainly considered a hospital-acquired infection, the emergence of new strains, some of which are pandemic, has resulted in community-acquired MRSA infections that often present as serious skin infections in otherwise healthy individuals. Accordingly, defining the mechanisms that govern the activation and regulation of the immune response to MRSA is clinically important and could lead to the discovery of much needed rational targets for therapeutic intervention. Because the cytokine thymic stromal lymphopoetin (TSLP) is highly expressed by keratinocytes of the skin3, we investigated its role in host-defense against MRSA. Here we demonstrate that TSLP acts on neutrophils to increase their killing of MRSA. In particular, we show that both mouse and human neutrophils express functional TSLP receptors. Strikingly, TSLP enhances mouse neutrophil killing of MRSA in both an in vitro whole blood killing assay and an in vivo skin infection model. Similarly, TSLP acts directly on purified human blood neutrophils to reduce MRSA burden. Unexpectedly, we demonstrate that TSLP mediates these effects both in vivo and in vitro by engaging the complement C5 system. Thus, TSLP increases MRSA killing in a neutrophil- and complement-dependent manner, revealing a key connection between TSLP and the innate complement system, with potentially important therapeutic implications for control of MRSA infection.
2016-11-18 | GSE73313 | GEO
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.
2010-11-15 | GSE20541 | GEO