Project description:We investigated a paradoxical re-growth of E. coli upon treatment of a novel siderophore-conjugate, LP-600, at concentrations 16-32 times above the minimum inhibitory concentration (MIC).Transcriptome analysis revealed that LP-600 induced the expression of genes involved in SOS response and e14 prophage upon regrowth conditions.
Project description:The gene expression profiles of Mtb after treatment at the minimal inhibitory concentration (MIC) or 4 X MIC at an early stage (up to 6 hours) was compared to untreated Mtb.
Project description:The gene expression profiles of Mtb after treatment at the minimal inhibitory concentration (MIC) or 4 X MIC at an early stage (up to 6 hours) was compared to untreated Mtb. Our experiment is designed to in order to ensure that the primary effects (0-6h) of the drugs and any dose (1X MIC and 4X MIC) responses would be captured.
Project description:The ability of Mycobacterium tuberculosis (Mtb) to adopt heterogeneous physiological states, underlies it’s success in evading the immune system and tolerating antibiotic killing. Drug tolerant phenotypes are a major reason why the tuberculosis (TB) mortality rate is so high, with over 1.8 million deaths annually. To develop new TB therapeutics that better treat the infection (faster and more completely), a systems-level approach is needed to reveal the complexity of network-based adaptations of Mtb. Here, we report the transcriptional response of Mtb to the drug pretomanid. We performed transcriptomic sequencing (RNA-seq) on Mtb bacilli at 4, 24, 72 h following exposure to the drug.
Project description:We obtained a strain of oxytetracycline-resistant Edwardsiella tarda named LTB4-ROTC through artificial passaging in the TSB medium,the minimum inhibitory concentration (MIC) of LTB4-ROTC was 12.5 μg/mL, which was 32 folds increase contrast to LTB4-S strain. Proteomic analysis was conducted to profile the different protein expression.
Project description:We applied RNAseq (Nextseq) technology to study mechanism of action of nitro-containing heterocycle antitubercular JSF-2019, with des-nitro JSF-2026 as control. Briefly, mid-log phase (OD = 0.3) M. tuberculosis culture was treated by 10x MIC of each compound in biological quadruplicates followed by mRNA extraction and RNAseq analysis. We find that JSF-2019 and pretomanid as intracellular NO• donors exhibited distinct transcriptional patterns comparing to extracellular iNOS inducer such as DETA/NO, therefore it suggests distinguished mechanisms of action between intracellular vs. extracellular NO• donors. We also observed that JSF-2019 upregulated a subset of FAS-II genes similar to isoniazid, indicating JSF-2019 inhibits intracellular mycolic acid biosynthesis.
Project description:We studied the effects of three classes of antibiotics (amoxicillin, chlortetracycline and enrofloxacin ) on P. multocida transcriptome using custom oligonucleotide microarrays from Nimblegen systems. All the 2015 genes of Pm70 were spotted on the array and hybridizations were carried out with RNA isolated from three independent cultures of Pm70 grown in the presence or absence of sub-minimum inhibitory (sub-MIC) doses of antibiotics. Differentially expressed genes were identified by ANOVA and Dunnett’s test. Biological modeling of the differentially expressed genes (DE) was carried out based on Clusters of Orthologous (COG) groups and network analysis in Pathway Studio. Keywords: Response to sub-MIC antibiotics
Project description:Rifampicin plays an important role during tuberculosis treatment, which historically contributed for shortening therapy; however, rifampicin resistance has been the intersection for the definition of multi (MDR-TB) and extensively (XDR-TB) resistant outcomes. A key aspect which has contributed for investigations of drug action/resistance is the understanding of the dynamic genome expression, as that analyzed by Proteomics. Proteins from the reference strain, Mycobacterium tuberculosis H37Rv were extracted after 12, 24 and 48 hours over rifampicin challenge at the minimal inhibitory concentration (0.03 μg•mL-1) and identified by LC-MS.