Functional analyses of unknown factors related to meningococcal pathogenesis with unnatural amino acids

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07550
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49050:Bacteriology-related
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Takahashi Hideyuki 国立感染症研究所, 細菌第一部, 室長 (60321866)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 髄膜炎菌 / 侵襲性感染症 / 非天然アミノ酸 / 病原性因子

Outline of Final Research Achievements

Our previous genetic analyses revealed that the hypothetical protein, NMB1345, plays a crucial role in meningococcal infection in human brain microvascular endothelial cells; In the present study, we developed a new method to genetically incorporate ncAAs-encoded photocrosslinking probes into N. meningitidis by utilizing a pyrrolysyl-tRNA synthetase/tRNAPyl pair and elucidated the biological function(s) of the NMB1345 protein. The results revealed that the NMB1345 protein directly interacts with PilE, a major component of meningococcal pili, and further physicochemical and genetic analyses showed that the interaction between the NMB1345 protein and PilE was important for both functional pilus formation and meningococcal infectious ability in N. meningitidis. The present study using this new methodology for N. meningitidis provides novel insights into meningococcal pathogenesis by assigning the function of a hypothetical protein.

Free Research Field

細菌学

Academic Significance and Societal Importance of the Research Achievements

機能未知な髄膜炎菌の病原性因子の機能を解明することにより、新たな髄膜炎菌の病原性機構の分子機序を明らかにし、新規の髄膜炎菌感染症の治療薬の開発の礎を基礎研究側から提供出来ることが期待される。