U01 UCSD MRSA Vancomycin Treatment BCP Data
Ontology highlight
ABSTRACT:
INSTRUMENT(S): maXis
ORGANISM(S): Staphylococcus Aureus (ncbitaxon:1280)
SUBMITTER: 
Bernhard Palsson
PROVIDER: MSV000082801 | MassIVE | Wed Aug 08 10:05:00 BST 2018
REPOSITORIES: MassIVE
Similar Datasets
Project description:Background: Telavancin is a novel semi-synthetic lipoglycopeptide derivative of vancomycin with a decylaminoethyl side chain that is active against Gram-positive bacteria including Staphylococcus aureus strains resistant to methicillin or vancomycin. This study describes transcriptome alterations in S. aureus strain ATCC29213 treated with telavancin for 15 min and 60 min in comparing with other agents treatment, including vancomycin, enduracidin, m-chlorophenylhydrazone.
2012-04-14 | GSE37272 | GEO
Project description:The precise mechanism and effects of antibiotics in host gene expression and immunomodulation in MRSA infection is unknown. Using a well characterized Methicillin Resistant Staphylococcus aureus (MRSA) isolate USA300 in a murine model of infection, we determined that linezolid and vancomycin induced differential production of bacterial toxins and host cytokines, differences in host gene expression, and differences in immunomodulators during MRSA bloodstream infection. A total of 35 A/J mice, categorized into seven groups (no infection; no infection with linezolid; no infection with vancomycin; 2 hour post-infection (hpi) S. aureus; 24 hpi S. aureus; 24 hpi S. aureus with linezolid; and 24 hpi S. aureus with vancomycin), were used in this study. Mice were injected with USA300 (6 x 106 CFU/g via i.p. route), then intravenously treated with linezolid (25 mg/kg) or vancomycin (25 mg/kg) at 2 hpi. Control and S. aureus infected mice were euthanized at each time point (2 h or 24h) following injection. Whole blood RNA was used for microarray; three cytokines and two S. aureus toxins [PantonValentine Leukocidin (PVL) and alpha hemolysin] were quantified in mouse serum by ELISA. S. aureus CFUs were significantly reduced in blood and kidney after linezolid or vancomycin treatment in S. aureus-infected mice. In vivo IL-1M-NM-2 in mouse serum was significantly reduced in both linezolid (p=0.001) and vancomycin (p=0.006) treated mice compared to untreated ones. IL-6 was significantly reduced only in linezolid treated (p<0.001) but not in vancomycin treated mice. However, another proinflammatory cytokine, TNF-M-NM-1, did not exhibit altered levels in either linezolid or vancomycin treated mice (p=0.3 and p=0.51 respectively). In vivo level of bacterial toxin, Panton-Valentine leukocidin, in mouse serum was significantly reduced only in linezolid treated mice (p=0.02) but not in vancomycin treated mice. There was no significant effect of either treatment in in vivo level of alpha hemolysin production. Unsupervised hierarchical clustering using the gene expression data from 35 microarrays revealed distinct clustering based on infection status and treatment group. Study of the antibiotic-specific difference in gene expression identified the number of genes uniquely expressed in response to S. aureus infection, infection with linezolid treatment, and infection with vancomycin treatment. Pathway associations study for the differentially expressed genes in each comparison group (Control vs. 24 h S. aureus infection, 24 h S. aureus infection vs. 24 h S. aureus linezolid, and 24 h S. aureus infection vs. 24 h S. aureus vancomycin) in mice using Kyoto Encyclopedia of Genes and Genomes (KEGG) identified toll-like receptor signaling pathway to be common to every comparison groups studied. Glycerolipid metabolism pathway was uniquely associated only with linezolid treatment comparison group. The findings of this study provide the evidence that protein synthesis inhibitor like linezolid does a better job in treating MRSA sepsis compared to cell wall acting antibiotics like vancomycin. To identify differences in host gene expression in a murine sepsis model treated with a) linezolid and b) vancomycin, we used whole blood gene expression (RNA) signatures from A/J inbred mice infected with USA 300 MRSA to evaluate differences in host gene expression among mice treated with linezolid and vancomycin. We used 5 RNA samples from MRSA-infected, linezolid- or vancomycin-treated mice. A total of 7 experimental groups have been employed: 1) Uninfected control group: (negative controls). 2) Uninfected, linezolid-treated group: Uninfected, linezolid-treated mice. 3) Uninfected vancomycin-treated group: Uninfected, vancomycin-treated mice. 4) Infected control group (positive control 2 h) MRSA-infected, untreated mice. 5) Infected control group (positive control 24 h): MRSA-infected, untreated mice. 6) Infected linezolid group: MRSA-infected, linezolid-treated mice. 7) Infected vancomycin group: MRSA-infected, vancomycin-treated mice.
2014-06-05 | E-GEOD-38531 | biostudies-arrayexpress
Project description:The precise mechanism and effects of antibiotics in host gene expression and immunomodulation in MRSA infection is unknown. Using a well characterized Methicillin Resistant Staphylococcus aureus (MRSA) isolate USA300 in a murine model of infection, we determined that linezolid and vancomycin induced differential production of bacterial toxins and host cytokines, differences in host gene expression, and differences in immunomodulators during MRSA bloodstream infection. A total of 35 A/J mice, categorized into seven groups (no infection; no infection with linezolid; no infection with vancomycin; 2 hour post-infection (hpi) S. aureus; 24 hpi S. aureus; 24 hpi S. aureus with linezolid; and 24 hpi S. aureus with vancomycin), were used in this study. Mice were injected with USA300 (6 x 106 CFU/g via i.p. route), then intravenously treated with linezolid (25 mg/kg) or vancomycin (25 mg/kg) at 2 hpi. Control and S. aureus infected mice were euthanized at each time point (2 h or 24h) following injection. Whole blood RNA was used for microarray; three cytokines and two S. aureus toxins [PantonValentine Leukocidin (PVL) and alpha hemolysin] were quantified in mouse serum by ELISA. S. aureus CFUs were significantly reduced in blood and kidney after linezolid or vancomycin treatment in S. aureus-infected mice. In vivo IL-1β in mouse serum was significantly reduced in both linezolid (p=0.001) and vancomycin (p=0.006) treated mice compared to untreated ones. IL-6 was significantly reduced only in linezolid treated (p<0.001) but not in vancomycin treated mice. However, another proinflammatory cytokine, TNF-α, did not exhibit altered levels in either linezolid or vancomycin treated mice (p=0.3 and p=0.51 respectively). In vivo level of bacterial toxin, Panton-Valentine leukocidin, in mouse serum was significantly reduced only in linezolid treated mice (p=0.02) but not in vancomycin treated mice. There was no significant effect of either treatment in in vivo level of alpha hemolysin production. Unsupervised hierarchical clustering using the gene expression data from 35 microarrays revealed distinct clustering based on infection status and treatment group. Study of the antibiotic-specific difference in gene expression identified the number of genes uniquely expressed in response to S. aureus infection, infection with linezolid treatment, and infection with vancomycin treatment. Pathway associations study for the differentially expressed genes in each comparison group (Control vs. 24 h S. aureus infection, 24 h S. aureus infection vs. 24 h S. aureus linezolid, and 24 h S. aureus infection vs. 24 h S. aureus vancomycin) in mice using Kyoto Encyclopedia of Genes and Genomes (KEGG) identified toll-like receptor signaling pathway to be common to every comparison groups studied. Glycerolipid metabolism pathway was uniquely associated only with linezolid treatment comparison group. The findings of this study provide the evidence that protein synthesis inhibitor like linezolid does a better job in treating MRSA sepsis compared to cell wall acting antibiotics like vancomycin.
2014-06-05 | GSE38531 | GEO
Project description:Investigation of baseline transcription activity of two different clinical isolates of Staphylococcus aureus with two different susceptibility levels to the antibiotics Vancomycin and Daptomycin. Two different strains of Staphylococcus aureus, one that is fully Vancomycin and Daptomycin Sensitive and one with decreased Vancomycin and Daptomycin Sensitivity - grown to mid-log phase in rich broth.
2012-08-03 | E-GEOD-39868 | biostudies-arrayexpress
Project description:To determine if significant genomic changes are associated with the development of vancomycin intermediate Staphylococcus aureus, genomic DNA microarrays were performed to compare the initial vancomycin susceptible Staphylococcus aureus (VSSA) and a related vancomycin intermediate Staphylococcus aureus (VISA) isolate from five unique patients (five isolate pairs). Keywords: comparative genomic hybridization
2006-11-03 | GSE5047 | GEO
Project description:Vancomycin Intermediate Staphylococcus aureus (VISA) strain originated during the prolonged hospitalization, chronic infection and vancomycin treatment. The hospital acquired D712 VISA strain were subjected to various sub-inhibitory concentration of nafcillin in Cation Adjusted Mueller Hinton Broth (CA-MHB) and Roswell Park Memorial Institute (RPMI) medium. The MIC of has dropped from 256 ug/ml to 1ug/ml in CA-MHB and RPMI media respectively. The cells were harvested and expression profiling were measured using RNA sequencing at time point of 03 hours.
2019-10-22 | GSE139141 | GEO
Project description:Background: Telavancin is a novel semi-synthetic lipoglycopeptide derivative of vancomycin with a decylaminoethyl side chain that is active against Gram-positive bacteria including Staphylococcus aureus strains resistant to methicillin or vancomycin. This study describes transcriptome alterations in S. aureus strain ATCC29213 treated with telavancin for 15 min and 60 min in comparing with other agents treatment, including vancomycin, enduracidin, m-chlorophenylhydrazone. MHB cultures (biological replicates: N=3) were then grown to exponential phase (OD580=0.35) before the addition of telavancin(8 M-BM-5g/ml final concentration), or vancomycin (10 /M-BM-5g ml) or CCCP (2 M-BM-5g/ ml ); or enduracidin (1 M-BM-5g ml) and incubated for an additional 15 min , and 60 min before sampling. Dye-swapping was performed between samples.
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Project description:Novel anti-infective agents targeting Staphylococcus aureus and capable of increasing S. aureus susceptibility towards antibiotics are needed. One alternative approach is targeting the bacterial quorum sensing (QS) system. QS is a process by which bacteria produce and detect signal molecules and thereby coordinate their behaviour, virulence and biofilm formation in a cell-density-dependent manner. Hamamelitannin (HAM) was previously suggested to target the S. aureus QS system, thereby increasing the susceptibility of S. aureus biofilms towards vancomycin. However, mechanistic insights are still lacking. For this reason, we evaluated the effect of Hamamelitannin, vancomycin and combination treatment of Hamamelitannin and vancomycin on gene expression in S. aureus Mu50 biofilms.
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2013-06-10 | E-GEOD-40864 | biostudies-arrayexpress
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