Project description:Epidermal growth factor receptor (EGFR) mutations are an oncogenic driver in non-small cell lung cancer (NSCLC), but resistance to EGFR tyrosine kinase inhibitors (TKIs) remains a major challenge. Here, we show that mycoplasma infection sustains ERK, AKT, and NF-κB signaling, impairs receptor internalization, and reduces osimertinib sensitivity in EGFR-mutant NSCLC cells. Antibiotic-mediated clearance of Mycoplasma partially restored drug sensitivity, establishing a causal infection-resistance link. Transcriptomic analysis identified converging pathways related to mycoplasma infection and drug resistance, including gene sets enriched for inhibition of receptor internalization and clathrin downregulation at the protein level. Combined inhibition of mTOR and LDHA improved growth suppression in mycoplasma-positive cells. Clinically, mycoplasma infection and higher LDHA expression were associated with poor overall survival of EGFR-TKI-treated patients. These findings establish mycoplasma infection as a causal, non-genetic contributor to EGFR-TKI resistance and support a hierarchical therapeutic strategy combining antibiotic eradication with mTOR and LDHA inhibition.
Project description:The immune response associated with mastitis caused by Mycoplasma bovis is a very complicated biological process in several type of cells, including immune cells, mammary epithelial cells and, endothelial cells. Thus, revealing of the microRNAs in the Mycoplasma bovis infected mammary gland tissues is particularly important for the immune response mechanism to Mycoplasma bovis. Firstly, mammary gland tissue samples were collected from Holstein cows and screened for Mycoplasma bovis. Then, total RNA was isolated from mycoplasma bovis infected tissues and RNA sequencing was performed. After bioinformatics analysis, GO and KEGG analysis of target genes of identified microRNAs were conducted. Our results revaled that 24 of the known microRNAs were expressed differently and 13 of the novel microRNAs were expressed differently in Mycoplasma bovis positive tissues. The target genes of these microRNAs were found to be associated with especially inflammation pathways. In conclusion, this study demonstrated that identified miRNAs may be involved in the signaling pathways during mastitis case caused by Mycoplasma bovis.
Project description:Mycoplasma gallisepticum transcriptome comparison between in vitro grown cultures of strains Rlow and F utilizing oligo DNA microarrays.
Project description:Analysis of H292 cells infected with Mycoplasma hyorhinis. Mycoplasma infection reduces the cytotoxic effect of Nutlin3 on H292 cells. The results provide insight into molecular mechanisms underlying the response of H292 cells to Nutlin3.
