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Staphylococcus aureus strain:USA300_FPR3757 | isolate:JE2

ABSTRACT: Staphylococcus aureus USA300 Lac JE2 derivatives with increased resistant to alkylguanidinium compound L15 shotgun genomics raw reads

PROVIDER: PRJNA1103407 | ENA |

REPOSITORIES: ENA

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Dataset's files

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			Action	DRS
	SRR28781444_1.fastq.gz	Fastqsanger.gz
	SRR28781444_2.fastq.gz	Fastqsanger.gz
	SRR28781445_1.fastq.gz	Fastqsanger.gz
	SRR28781445_2.fastq.gz	Fastqsanger.gz
	SRR28781446_1.fastq.gz	Fastqsanger.gz

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Screening privileged alkylguanidinium motifs under host-mimicking conditions reveals a novel antibiotic with an unconventional mode of action

Project description:Screening large molecule libraries against pathogenic bacteria is often challenged by a low hit rate due to limited uptake, underrepresentation of antibiotic structural motifs and assays which do not resemble the infection conditions. To address these limitations, we here screen a library focused on alkylguanidinium compounds, a structural motif associated with antibiotic activity and enhanced uptake, under host-mimicking infection conditions against a panel of disease-associated bacteria. Several hit molecules were obtained with activities against Gram-positive as well as Gram-negative bacteria highlighting the fidelity of the general concept. Based on the best antibiotic activity, we selected one compound (L15) for in-depth mode of action studies. L15 exhibited bactericidal activity against Staphylococcus aureus USA300 Lac (JE2) with a minimum inhibitory concentration of 1.5 µM whereby a structure-activity relationship study with 18 derivatives proved the necessity of the guanidinium motif for antibiotic activity. Electron microscopy studies and depolarization assays at high L15 concentrations showed an impact on the cell membrane and integrity which was absent at the MIC concentration. Sequencing of L15-resistant strains revealed a mutation in an efflux pump but did not provide hints for direct targets. We thus performed affinity-based protein profiling with a L15 probe and identified signal peptidase IB (SpsB) as the most promising hit. Validation by activity assays, binding site identification and molecular docking demonstrated SpsB overactivation by L15, similar to a previously reported activator molecule that dysregulates protein secretion of this essential enzyme. Overall, this study highlights the need for unconventional screening strategies to identify novel antibiotics.

2024-07-17 | PXD051986 | Pride

Determination of Transcriptional start sites in S. aureus USA300 (JE2) during exponential phase

Project description:Transcriptional start sites determination of USA300 (JE2) by using dRNA-Seq

2016-05-04 | GSE67424 | GEO

RNA-Seq based comparison of Staphylococcus aureus strains resistent and sensitive to MT02

Project description:A MT02 sensitive and resistant strain of Staphylococcus LAC USA300 JE2 were exposed to MT02. From those cell RNA was extracted and anylsed by RNA-Seq

2017-11-05 | GSE87572 | GEO

LC-MS of extracellular vesicles from Staphylococcus aureus USA300 JE2 and its agrspa double mutant strain

Project description:This project aims to identify the extracellular vesicles (EVs) from Staphylococcus aureus USA300 JE2 strain. In addition, we also detoxified the EVs by mutation of agr ad spa genes in JE2 and evaluated the immunogenicity and protection of the detoxified EVs. These proteins from these detoxified EVs were also identified by MS.

2018-10-23 | PXD007953 | Pride

Protein compositions of extracellular vesicles released from Staphylococcus aurues JE2 and its lgt mutant

Project description:This project detected the protein composition of extracellular vesicles (EV) produced by S. aureus WT JE2 strain and its lgt mutant (lipoprotein deficient mutant). Our recent study found that mutation of lgt in S. aureus USA300 JE2 strain significantly increased EV production in S. aureus and decreased the pore-forming toxin content of vesicles, indicatiung that lipoproteins modulate the EV biogenesis of S. aureus. To gain a better understanding of this process, we detected the protein compositions associated with EVs purified from both WT and lgt mutant EVs by LC-MS/MS. Compared to WT EVs, more cytosoli proteins and less extracellular proteins were identified in lgt mutant EVs. A total of 180 and 198 proteins were identified from WT and lgt mutant EVs, respectively.In addition 27.2% and 33.8% of identified proteins were unique to WT or lgt mutant EVs respectively.

2021-09-08 | PXD014888 | Pride

bacterium JE2

Project description:bacterium JE2 Raw sequence reads

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Expression analysis of Staphylococcus aureus USA300 LAC in response to vehicle and benzbromarone.

Project description:Compilation fo whole genome gene expression changes in Staphylococcus aureus USA300 LAC cultures grown in the presence of vehicle or the anti-gout drug benzbromarone. The drug was intially screened as effective against the agr quorum sensing system in Staphylococcus aureus AH1677. A microarray study using total RNA harvested from three cultures of Staphylococcus aureus USA300 LAC plus vehicle control and three cultures of Staphylococcus aureus USA300 LAC plus 12 uM benzbromarone.

2014-03-19 | E-GEOD-55980 | biostudies-arrayexpress

Prophage-encoded methyltransferase upregulates virulence to drive adaptation in an outbreak of community-acquired methicillin-resistant Staphylococcus aureus [Harm analysis]

Project description:To determine the effects of phage m⏀11 on gene expression in USA300 (LAC*)

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Prophage-encoded methyltransferase upregulates virulence to drive adaptation in an outbreak of community-acquired methicillin-resistant Staphylococcus aureus

Project description:To determine the effects of phage adenine methyltransferase (pamA) on gene expression in WT USA300 (LAC*)

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