Influence of Staphylococcus aureus biofilm infection phase on functional composition of host neutrophils
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE264548 | GEO | 2024/07/03
REPOSITORIES: GEO
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Project description:S. epidermidis ability to form biofilms on indwelling medical devices and its association with the emergence of chronic infections is its main virulence factor. Nevertheless, it has been shown that the cells released from these biofilms are associated with the advent of serious acute infections with bacteraemia as one of the major clinical manifestations. Despite their clinical relevance, very little is known about the impact of biofilm-released cells in pathogenesis. Hence, herein, we characterized the murine immune response to the presence of cells released from S. epidermidis biofilms analysing spleen cells transcriptome by microarrays. These findings may help to explain the recurrent inflammatory symptoms presented by patients with colonization of indwelling medical devices.
2017-02-22 | GSE60992 | GEO
Project description:Staphylococcus aureus is a notorious biofilm-producing pathogen that is frequently isolated from implantable medical device infections. As biofilm ages, it becomes more tolerant to antimicrobial treatment leading to treatment failure and necessitating the costly removal of infected devices. In this study, we investigated what changes occur in the proteome of S. aureus biofilm grown for 3-days and 12-days in comparison with 24 h planktonic showed that proteins associated with bi-osynthetic processes, ABC transporter pathway, virulence proteins, and shikimate kinase pathway were significantly upregulated in 3-day biofilm, while proteins associated with sugar transporter, degradation, and stress response were downregulated. In 12-day biofilms, proteins associated with peptidoglycan biosynthesis, sugar transporters, and stress responses were upregulated, whereas proteins associated with ABC transporters, DNA replication, and adhesion proteins were down-regulated. Furthermore, we observed significant variations in the formation of biofilms result from changes in the level of metabolic activity in the different growth mode of biofilms that could be a significant factor of S. aureus biofilm maturation and persistence. Collectively, potential marker proteins were identified and further characterized to understand their exact role in S. aureus biofilm development which may shed light on possible new therapeutic regimes in the treatment of biofilm-related implant-associated infections.
2022-08-12 | PXD033499 | Pride
Project description:Biofilms are sessile microbial communities that are often resistant to conventional antimicrobial therapeutics and the host immune system. Candida albicans is an opportunistic pathogenic yeast and responsible for candidiasis. It readily colonizes host tissues and implant devices, and forms biofilms, which play an important role in pathogenesis and drug resistance. Its morphological transition from budding yeast to hyphal form and subsequent biofilm formation is regarded as the crucial factor for drug tolerance and virulence of Candida infections. In this study, nepodin (also called musizin) from Rumex japonicus root was investigated for antibiofilm, antihyphae, and antivirulence activities against fluconazole-resistant C. albicans strain. Nepodin at 2 µg/ml from Rumex plant effectively inhibited C. albicans biofilm formation by more than 90% but had no effect on planktonic cell growth. Also, Rumex root extract and nepodin inhibited hyphal growth and cell aggregation of C. albicans. Interestingly, nepodin also showed antibiofilm activity against Staphylococcus aureus or A. baumannii strains and two systems of dual biofilms of C. albicans and S. aureus or A. baumannii, respectively. Transcriptomic analysis using RNA-seq and qRT-PCR showed nepodin repressed the expressions of several hypha/biofilm related genes (ECE1, HWP1, and UME6) and overexpressed several transport genes (CDR4, CDR11, IFD6, and TPO2), which supported observed phenotypic changes.
2021-09-01 | GSE119822 | GEO
Project description:Acinetobacter baumannii is a Gram-negative ESKAPE pathogen, accountable for lethal nosocomial infections, owing to its high pathogenicity and multi-drug resistance (MDR). Hence, the World Health Organization (WHO) has prioritized this bacterium against which new pharmacophores are required urgently. Therefore, this study evaluates the antimicrobial potential of lithium complex based on salicylic acid, and 1,10-phenanthroline ([Li(phen)2sal]) against MDR A. baumannii (MDRAB) through growth inhibition, time-kill assay, biofilm inhibition, and eradication alongside microscopy. The mechanism of action was proposed by flow cytometry and proteomic analysis. Moreover, its in-vivo efficacy was assessed using A. baumannii-induced pneumonia model in mice. Results showed that lithium complex significantly inhibited the bacterial growth at 16-32 µg/ml. Time kill analysis revealed that the compound retarded the bacterial growth after 2-3 h of treatment. Lithium complex significantly inhibited and eradicated >70% of biofilms at the MIC level which is a key problem of indwelling and prosthetic devices. Light and atomic force microscopy further indicated disarticulated biofilm and ruptured cellular membrane post-lithium complex treatment. Proteomic analysis revealed that lithium complex exerted oxidative stress on A. baumannii which may contribute to cell rupturing. Flow cytometry confirmed the role of lithium complex in cytoplasmic membrane disintegration. The compound ameliorated the pneumonia symptoms at non-toxic doses of 20 and 40 mg/kg in the pre-clinical A. baumannii-induced pneumonia model as evident by the significant reduction in bacterial burden and parenchymal inflammation. Taken together, these findings suggest that the lithium complex can be a potential drug candidate against MDR A. baumannii.
2023-09-22 | PXD044293 | Pride
Project description:Staphylococcus epidermidis is a common causative of nosocomial infections associated with indwelling medical devices. To date, the mechanisms of the pathogenicity and drug resistance of S. epidermidis have not been clearly elucidated. AbfR has been previously identified as an oxidation-sensing regulator that regulates bacterial aggregation and biofilm formation by responding to oxidative stress in S. epidermidis; however, the regulatory pathways of AbfR are underexplored. In this study, we investigated the oxidation-sensing regulatory mechanism of AbfR using TMT10-plex labelling quantitative proteomic and untargeted metabolomic approaches. Integrated analysis of two omics datasets indicated that abfR depletion influenced nucleic acid metabolism and activated the DNA mismatch repair pathway. In addition, several energy-related metabolic pathways, including tricarboxylic acid (TCA) cycle, glycolysis, and arginine metabolism, were remarkably impacted by the deletion of abfR. This study revealed the regulatory networks of the transcription factor AbfR from a multi-omics view and demonstrated that AbfR played a broad role in not only mismatch repair but also energy metabolism, enabling S. epidermidis to constantly sense and adapt to environmental stress.
2020-07-29 | PXD020096 | Pride
Project description:Biofilm formation on medically implanted devices by Candida albicans poses a significant clinical challenge. Here we compared biofilm-associated gene expression in two clinical C. albicans isolates, SC5314 and WO-1, to identify shared gene regulatory responses that may be functionally relevant. Among the 50 genes most highly expressed in biofilms relative to planktonic (suspension-grown) cells, we were able to recover insertion mutations in 25 genes. We observed that 20 of the 25 mutants have altered biofilm-related properties, including cell-substrate adherence, cell-cell signaling, and azole susceptibility. We focused on the most highly up-regulated gene in biofilms, RHR2, which specifies the glycerol biosynthetic enzyme glycerol-3-phosphate phosphatase. Glycerol is 5-fold more abundant in biofilm cells than planktonic cells, and an rhr2D/D strain accumulates 2-fold less biofilm glycerol than the wild type. Under in vitro growth conditions, the rhr2D/D mutant has reduced biofilm biomass and reduced adherence to silicone. The rhr2D/D mutant is severely defective in biofilm formation in vivo, in a rat catheter infection model. Expression profiling of the rhr2D/D mutant indicates that it has reduced expression of cell surface adhesin genes ALS1, ALS3, and HWP1, as well as a large fraction of all other biofilm up-regulated genes. Reduced adhesin expression is the cause of the rhr2D/D mutant biofilm defect, because overexpression of ALS1, ALS3, or HWP1 restores biofilm formation ability to the mutant in vitro and in vivo. Our findings indicate that internal glycerol has a regulatory role in biofilm gene expression, and that adhesin genes are among the main functional Rhr2-regulated genes.
2013-04-12 | GSE45141 | GEO
Project description:Human gingival epithelial cells (HGEp) and fibroblasts (HGF) are the main cell types of the peri-implant soft-tissue, with HGEp constantly being exposed to bacteria and HGF residing protected in the connective tissue as long as an intact mucosa-implant seal is preserved. Streptococcus oralis belongs to the commensal bacteria, is highly abundant at healthy implant sites, and might exert host modulatory effects on soft-tissue cells as described for other streptococci. Thus, we aimed to investigate the effects of S. oralis biofilm on HGEp as well as HGF. HGEp or HGF were grown on titanium separately and responded to S. oralis biofilm challenge. The cell condition of HGF was dramatically impaired after 4 hours showing a transcriptional inflammatory and stress response. In contrast, S. oralis challenge induced only transcriptional inflammatory response in HGEp with their cell condition remaining unaffected. Subsequently, HGF were susceptible compared to HGEp. The proinflammatory IL-6 was attenuated in HGF and CXCL8 in HGEp indicating a general tissue-protective role of S. oralis, forasmuch as the HGF are not exposed. In conclusion, an intact implant-mucosa interface is a prerequisite so that commensal biofilms can promote homeostasis for tissue protection.
2020-06-17 | GSE134481 | GEO
Project description:The formation of biofilms is closely associated with persistent and chronic infections, and physiological heterogeneity such as pH and oxygen gradients renders biofilms highly resistant to conventional antibiotics. To date, effectively treating biofilm infections remains a significant challenge. Herein, we report the fabrication of micellar nanoparticles adapted to heterogeneous biofilm microenvironments, enabling nitric oxide (NO) release through two distinct photoredox catalysis mechanisms. The key design feature involves the use of tertiary amine (TA) moieties, which function as sacrificial agents to avoid the quenching of photocatalysts under normoxic and neutral pH conditions and proton acceptors at acidic pH to allow deep biofilm penetration. This biofilm-adaptive NO-releasing platform shows excellent antibiofilm activity against ciprofloxacin-resistant Pseudomonas aeruginosa (CRPA) biofilms both in vitro and in a mouse skin infection model, providing a strategy for combating biofilm heterogeneity and biofilm-related infections.
2023-11-22 | GSE246965 | GEO
Project description:The opportunistic bacterium Pseudomonas aeruginosa is a major nosocomial pathogen causing both devastating acute and chronic persistent infections. During the course of an infection, P. aeruginosa rapidly adapts to the specific conditions within the host. In the present study, we aimed at the identification of genes that are highly expressed during biofilm infections such as in chronically infected lungs of patients with cystic fibrosis (CF), burn wounds and subcutaneous mouse tumours. We found a common subset of differentially regulated genes in all three in vivo habitats and evaluated whether their inactivation impacts on the bacterial capability to form biofilms in vitro and to establish biofilm-associated infections in a murine model. Additive effects on biofilm formation and host colonization were discovered by the combined inactivation of several highly expressed genes. However, even combined inactivation was not sufficient to abolish the establishment of an infection completely. These findings can be interpreted as evidence that either redundant traits encode functions that are essential for in vivo survival and chronic biofilm infections and/or bacterial adaptation is considerably achieved independently of transcription levels. Supplemental screens, will have to be applied in order to identify the minimal set of key genes essential for the establishment of chronic infectious diseases.
2012-11-14 | GSE25945 | GEO
Project description:The opportunistic bacterium Pseudomonas aeruginosa is a major nosocomial pathogen causing both devastating acute and chronic persistent infections. During the course of an infection, P. aeruginosa rapidly adapts to the specific conditions within the host. In the present study, we aimed at the identification of genes that are highly expressed during biofilm infections such as in chronically infected lungs of patients with cystic fibrosis (CF), burn wounds and subcutaneous mouse tumours. We found a common subset of differentially regulated genes in all three in vivo habitats and evaluated whether their inactivation impacts on the bacterial capability to form biofilms in vitro and to establish biofilm-associated infections in a murine model. Additive effects on biofilm formation and host colonization were discovered by the combined inactivation of several highly expressed genes. However, even combined inactivation was not sufficient to abolish the establishment of an infection completely. These findings can be interpreted as evidence that either redundant traits encode functions that are essential for in vivo survival and chronic biofilm infections and/or bacterial adaptation is considerably achieved independently of transcription levels. Supplemental screens, will have to be applied in order to identify the minimal set of key genes essential for the establishment of chronic infectious diseases. Ex-vivo samples were collected from burn wound, cystic fibrosis patients mucous and mice tumor and stabilized for the RNA extraction. Recovered clinical strains were cultivated in rich medium control conditions untill the early stationary phase and RNA was extracted. The murine tumors were infected with burn wound isolated strains
2012-11-14 | E-GEOD-25945 | biostudies-arrayexpress