Third Military Medical University, China
Xuhu Mao is a full professor of Clinical Microbiology and Immunology in Third Military Medical University. He has been the Chief of Department since September 2013. His research specifically focuses on understanding the interaction between pathogens and host. He has published more than 30 papers in reputed journals, which deal with the molecular mechanisms of bacterial pathogenesis. Qian Li is a third year PhD student in Third Military Medical University, whose major is the Microbiology. Currently, She is studying in Dan Luo’s lab of Cornell University, as a “jointly-supervised” PhD student, centering on applying DNA nanotechnology in point-of-care pathogen detection.
Burkholderia pseudomallei is a notorious pathogen of human meloidosis, which is classically characterized by pneumonia and multiple abscesses with a high mortality and relapse rate. Autophagy as one of the earliest defense responses encountered by intracelluar pathogens, is a process that engulfs and delivers intracellular bacteria for lysosomal degradation. Recent studies indicate that B. pseudomallei can survive inside mammalian cell lines owning to its ability to evade autophagy in an active behavior. However, the associated mechanisms remain to be established. In our study, in order to reveal the underlying mechanisms, levels of mRNA and miRNAs in human lung epithelial A549 cells during B. pseudomallei infection were measured using microarray assay. We showed that ATG10, an important regulator of autophagy, was downregulated during B. pseudomallei infection in A549 cells. Furthermore, overexpression of ATG10 promoted to eliminate intracellular B. pseudomallei by enhancing the process of autophagy. As a potential mechanistic explanation for this observation, we demonstrated that three novel miRNAs, MIR4458, MIR4667-5p and MIR4668-5p, bound to the 3’-untranslated region of ATG10, by different time course and spatial manner. Upregulation of these miRNAs reduced the level of ATG10 and inhibited autophagy, leading to increased numbers of intracellular B. pseudomallei. These results suggest that infection with B. pseudomallei upregulates miRNAs to reduce expression of protein required for autophagy and autophagy response in lung epithelial cells.
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