Staphylococcus aureus
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PROVIDER: PRJNA309388 | ENA |
REPOSITORIES: ENA
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Project description:It is very important to understand the mechanisms how bacteria become tolerant towards antibiotics during clinical therapy. In a previous study we showed that increased daptomycin (DAP) tolerance of Staphylococcus aureus was due to a point mutation in pitA (inorganic phosphate transporter) that led to intracellular accumulation of both inorganic phosphate (Pi) and polyphosphate (polyP). DAP tolerance in that pitA6 mutant differs from classical resistance mechanisms as there was no increase in minimal inhibitory concentration (MIC). In this study we demonstrate that DAP tolerance in the pitA6 mutant is not triggered by the accumulation of polyP. Transcriptome analysis revealed that about 234 genes were at least 2.0-fold differently expressed in the mutant. Particularly, genes involved in protein biosynthesis, carbohydrate and lipid metabolism as well as in replication and maintenance of DNA were downregulated. However, the most important change was the upregulation of the dlt-operon, which is induced by the accumulation of intracellular Pi. The GraXRS system, known as activator of both dlt and mprF, as well as surface charge, cell wall thickness or the content of wall teichoic acids (WTA) are not involved in DAP tolerance in the pitA6 mutant. In conclusion the DAP tolerance in the pitA6 mutant is due to an upregulation of the dlt-operon triggered directly or indirectly by the accumulation of Pi. WT strain HG003 and its pitA mutant were used to compare transcriptomic changes after 6 or 8 hours of growth in suspension in TSB medium
2016-02-10 | E-GEOD-77069 | biostudies-arrayexpress
Project description:It is very important to understand the mechanisms how bacteria become tolerant towards antibiotics during clinical therapy. In a previous study we showed that increased daptomycin (DAP) tolerance of Staphylococcus aureus was due to a point mutation in pitA (inorganic phosphate transporter) that led to intracellular accumulation of both inorganic phosphate (Pi) and polyphosphate (polyP). DAP tolerance in that pitA6 mutant differs from classical resistance mechanisms as there was no increase in minimal inhibitory concentration (MIC). In this study we demonstrate that DAP tolerance in the pitA6 mutant is not triggered by the accumulation of polyP. Transcriptome analysis revealed that about 234 genes were at least 2.0-fold differently expressed in the mutant. Particularly, genes involved in protein biosynthesis, carbohydrate and lipid metabolism as well as in replication and maintenance of DNA were downregulated. However, the most important change was the upregulation of the dlt-operon, which is induced by the accumulation of intracellular Pi. The GraXRS system, known as activator of both dlt and mprF, as well as surface charge, cell wall thickness or the content of wall teichoic acids (WTA) are not involved in DAP tolerance in the pitA6 mutant. In conclusion the DAP tolerance in the pitA6 mutant is due to an upregulation of the dlt-operon triggered directly or indirectly by the accumulation of Pi.
2016-02-10 | GSE77069 | 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:Daptomycin is a lipopeptide antibiotic that has recently been approved for treatment of Gram-positive bacterial infections. The mode of action of daptomycin is not yet entirely clear. To further understand the mechanism transcriptomic analysis of changes in gene expression in daptomycin-treated Staphylococcus aureus was carried out. The expression profile indicated that cell wall stress stimulon member genes (B. J. Wilkinson, A. Muthaiyan, and R. K. Jayaswal. 2005. Curr. Med. Chem. Anti-Infective Agents 4: 259-276) were significantly induced by daptomycin, and by the cell wall-active antibiotics vancomycin and oxacillin. Comparison of the daptomycin response of a two-component cell wall stress stimulon regulator VraSR mutant, S. aureus KVR, to its parent N315 showed diminished expression of the cell wall stress stimulon in the mutant. Daptomycin has been proposed to cause membrane depolarization, and the transcriptional responses to carbonyl cyanide m-chlorophenylhydrazone (CCCP) and nisin were determined. Transcriptional profiles of the responses to these antimicrobial agents showed significantly different patterns compared to those of the cell wall-active antibiotics, including little or no induction of the cell wall stress stimulon. However, there were a significant number of genes induced by both CCCP and daptomycin that were not induced by oxacillin or vancomycin, such that the daptomycin transcriptome was probably reflecting a membrane depolarizing activity of this antimicrobial also. The results indicate that inhibition of peptidoglycan biosynthesis, either directly or indirectly, and membrane depolarization are parts of the mode of action of daptomycin. Keywords: mode of action, transcriptional profiling
2007-12-25 | GSE9494 | 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.
2012-08-03 | GSE39868 | GEO
Project description:To study the effect of Radix Paeoniae Rubra decoction on tolerance of Staphylococcus aureus.The effect of Radix Paeoniae Rubra on the resistance of Staphylococcus aureus to oxacillin sodium was studied by millipore dilution method in this experiment.At the same time ,conducted on transcriptome analysis of Staphylococcus aureus related genes in Radix Paeoniae Rubra.And to detect the expression level of related genes of Staphylococcus aureus under the action of Radix Paeoniae Rubra by PCR technology.The tolerance of Staphylococcus aureus was decreased obviously when the concentration of Radix Paeoniae Rubra decoction was above 1mg/ml.The effect of Radix Paeoniae Rubra decoction on the expression of tolerance genes femB,pvL and gluM when the concentration of Radix Paeoniae Rubra decoction was above 4mg/ml.When rhe concentration of Radix Paeoniae Rubra is more than 1mg/ml,it can effectively reduce the resistance of Staphylococcus aureus to oxacillin sodium.The reason may be due to the effect of Radix Paeoniae Rubra on the resistance gene of Staphylococcus aureus.
2021-01-30 | GSE165791 | GEO
Project description:Daptomycin is an extensively used anti-staphylococcal agent due to the rise in methicillin-resistant Staphylococcus aureus. However, both laboratory-derived and clinical decreased susceptibility isolates have been described, but the mechanism(s) of resistance is poorly understood. To further understand daptomycin resistance, comparative genome sequencing, transcriptomics, ultrastructure ,and cell envelope studies were carried out on two relatively higher level (4 and 8 ug/ml-1) laboratory-derived daptomycin-resistant strains (strains CB1541 and CB1540 respectively) compared to their methicillin-resistant parent strain (CB1118;MW2). Genes altered in their expression common to both transcriptomes included some involved in glycine betaine accumulation, mscL, ure genes, femH, spa and smpB. However, the CB1541 transcriptome was further characterized by upregulation of various heat shock chaperone and protease genes, consistent with a mutation in clpP, and lytM and sceD. Both strains showed slow growth, and strongly decreased autolytic activity that appeared to be mainly due to decreased autolysin production. In contrast to previous common findings, we did not find any mutations in phospholipid biosynthesis genes, and it appears there are multiple pathways to and factors in daptomycin resistance.
2012-10-01 | GSE40753 | GEO
Project description:Objectives: Development of daptomycin resistance (DAPR) in Staphylococcus aureus is associated with clinical treatment failures. Mechanism(s) of such resistance has not been clearly defined. Methods: We studied an isogenic daptomycin-susceptible (DAPS) and daptomycin-resistant (DAPR) S. aureus strain pair (616; 701) from a patient with relapsing endocarditis during daptomycin treatment, using comparative transcriptomic and proteomic techniques. Results. Minor differences in genome content were found between strains by DNA hybridization. Transcriptomic analyses identified a number of genes differentially expressed in important functional categories: cell division, metabolism of bacterial envelopes and global regulation. Of note, the DAPR isolate exhibited reduced expression of the major cell wall autolysis gene coincident with upregulation of genes involved in wall teichoic acid production. Using quantitative (q)RT-PCR on gene cadre putatively involved in cationic peptide resistance, we formulated a putative regulatory network compatible with microarray data-sets, mainly implicating bacterial envelopes. Of interest, qRT-PCR of this same gene cadre from two distinct isogenic DAPS/DAPR clinical strain pairs revealed evidence of other strain dependent networks operative in the DAPR phenotype. Comparative proteomics of 616 vs 701 revealed differential abundance of proteins in various functional categories including: cell-wall associated targets and biofilm-formation proteins. Phenotypically, strains 616 and 701 showed major differences in ability to develop bacterial biofilms in presence of the antibacterial lipid, oleic acid. Conclusions: Compatible with previous in vitro observations, in vivo acquired DAPR in S. aureus is a complex, multistep phenomenon allowing for: i) strain dependent phenotypes; ii) transcriptome adaptation; and iii) modification of lipid and protein content of cellular envelopes. Daptomycin suceptible strain vs daptomycin non suceptible strain after daptomycin treatment
2011-12-02 | E-GEOD-28632 | biostudies-arrayexpress
Project description:Staphylococcus aureus is responsible for a substantial number of invasive infections globally each year. These infections are problematic because they are frequently recalcitrant to antibiotic treatment. Antibiotic tolerance, the ability of bacteria to persist despite normally lethal doses of antibiotics, contributes to antibiotic treatment failure in S. aureus infections. To understand how antibiotic tolerance is induced, S. aureus biofilms exposed to multiple anti-staphylococcal antibiotics were examined using both quantitative proteomics and transposon sequencing. These screens indicated that arginine metabolism is involved in antibiotic tolerance within a biofilm and led to the hypothesis that depletion of arginine within S. aureus communities can induce antibiotic tolerance. Consistent with this hypothesis, inactivation of argH, the final gene in the arginine synthesis pathway, induces antibiotic tolerance. Arginine restriction was found to induce antibiotic tolerance via inhibition of protein synthesis. In a mouse skin infection model, an argH mutant has enhanced ability to survive antibiotic treatment with vancomycin, highlighting the relationship between arginine metabolism and antibiotic tolerance during S. aureus infection. Uncovering this link between arginine metabolism and antibiotic tolerance has the potential to open new therapeutic avenues targeting previously recalcitrant S. aureus infections.
2024-07-10 | GSE267626 | GEO
Project description:Treatment of stationary growth phase Staphylococcus aureus SA113 with 100-fold of the MIC of the lipopeptide antibiotic daptomycin leaves alive a small fraction of drug tolerant albeit genetically susceptible bacteria. This study shows that cells of this subpopulation exhibit active metabolism even hours after the onset of the drug challenge. Isotopologue profiling using fully 13C-labeled glucose revealed de novo biosynthesis of the amino acids Ala, Asp, Glu, Ser, Gly and His. The isotopologue composition in Asp and Glu suggested an increased activity of the TCA cycle under daptomycin treatment compared to unaffected stationary growth phase cells. Microarray analysis showed differential expression of specific genes 10 minutes and 3 hours after addition of the drug. Besides factors involved in drug response, a number of metabolic genes appear to shape the signature of daptomycin-tolerant S. aureus cells. These observations will be useful towards the development of new strategies against persisters and related forms of bacterial cells with downshifted physiology.
2014-06-06 | GSE57908 | GEO