• 作者： Yi-Yin Chen, Ching-Tai Huang, Shiao-Wen Li, Yi-Jiun Pan, Tzu-Lung Lin, Ya-Yu Huang, Ting-Hsuan Li, Yu-Ching Yang, Yu-Nong Gong and Yu-Chia Hsieh
• 作者服務機構： 1. Department of Pediatrics, Chang Gung Children’s Hospital, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan 2. Division of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taoyuan, Taiwan 3. Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan 4. Department of Microbiology and Immunology, School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan 5. Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan 6. Research Center for Emerging Viral Infections, Chang Gung University, Taoyuan, Taiwan 7. Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan 8. Department of Pediatrics, Chang Gung Children’s Hospital, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan 9. Department of Pediatrics, Linkou Chang Gung Memorial Hospital, No. 5, Fuxing Street, Guishan District, Taoyuan City, 333, Taiwan
• 中文摘要：
• 英文摘要：
  Background
  Streptococcus pneumoniae is a common cause of post-influenza secondary bacterial infection, which results in excessive morbidity and mortality. Although 13-valent pneumococcal conjugate vaccine (PCV13) vaccination programs have decreased the incidence of pneumococcal pneumonia, PCV13 failed to prevent serotype 3 pneumococcal disease as effectively as other vaccine serotypes. We aimed to investigate the mechanisms underlying the co-pathogenesis of influenza virus and serotype 3 pneumococci.
  
  Methods
  We carried out a genome-wide screening of a serotype 3 S. pneumoniae transposon insertion mutant library in a mouse model of coinfection with influenza A virus (IAV) to identify the bacterial factors required for this synergism.
  
  Results
  Direct, high-throughput sequencing of transposon insertion sites identified 24 genes required for both coinfection and bacterial infection alone. Targeted deletion of the putative aminotransferase (PA) gene decreased bacterial growth, which was restored by supplementation with methionine. The bacterial burden in a coinfection with the PA gene deletion mutant and IAV in the lung was lower than that in a coinfection with wild-type pneumococcus and IAV, but was significantly higher than that in an infection with the PA gene deletion mutant alone. These data suggest that IAV infection alters host metabolism to benefit pneumococcal fitness and confer higher susceptibility to pneumococcal infection. We further demonstrated that bacterial growth was increased by supplementation with methionine or IAV-infected mouse lung homogenates.
  
  Conclusions
  The data indicates that modulation of host metabolism during IAV infection may serve as a potential therapeutic intervention against secondary bacterial infections caused by serotype 3 pneumococci during IAV outbreaks in the future.
• 中文關鍵字：
• 英文關鍵字： Infuenza A, S. pneumoniae, Transposon mutant library, Coinfection, Metabolome