My research focuses on mechanisms of antimicrobial resistance and bacterial pathogenesis. For antimicrobial resistance, I have collaborated with Dr. Jing-Jou Yan, a pathologist at NCKU, with an emphasis on macrolide-resistance in group A streptococcus and b-lactamase-resistance of gram negative enteric bacteria.In group A streptococcus, we have found the high incidence and increasing rate of erythromycin-resistant GAS in southern Taiwan are due to the prevalence of multiple M-phenotype clones. In Klebsiella pneumoniae, we not only found that SHV-12 is the major ESBL strain in Taiwan but also discovered several novel b-lactamases (CMY-8, IMP-8) in our clinical isolates. IMP-8 and DHA-1- b are also found in our hospital outbreak strains.In E. coli, we found that CTX-M-3 and CMY-2 b-lactamase for the first time appeared in Asia, and dissemination of CMY-2 b -lactamase came from food animals and retail ground meats. In addition, we also found the interspecies spread and horizontal transfer of CMY-2 b-lactamase between E. coli, K. pneumoniae and Salmonella. For bacterial pathogenesis, I have collaborated with Dr. Bor-sheng Sheu, a gastroenterologist at NCKU, with an emphasis on the pathogenesis of Helicobacter pylori. We found that all the H. pylori isolates in Taiwan had a positive babA2 genotype and patients who expressed Lewis b had a higher H. pylori density than those who did not express Lewis b. However, for the patients without gastric Lewis b expression, H. pylori density was positively correlated with Lewis x and Lea expression. In addition to H. pylori, I have studied group A streptococcus (GAS) for many years. We found that streptococcal erythrogenic toxin B (SpeB) is associated with invasive group A streptococcal disease. We also demonstrated that SpeB not only enhances GAS invasion but also enhances apoptosis in U-937 and A549 cells. Furthermore, an animal study demonstrated SpeB is a very important virulence factor. We also found oligopeptide permease (Opp) of GAS plays an important role in virulence. Our data suggest that Opp not only positively- and negatively- regulated several virulence factors of GAS but also opened tight junctions between cells. Currently, the GAS project has been organized into a team. There are many PIs involved, which include a physician, cell biologist, protein chemist, immunologist, and microbiologist. Education
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