Open AccessAn intracellular nanobody targeting T4SS effector inhibits Ehrlichia infection
Author(s) -
Wenqing Zhang,
Mingqun Lin,
Qi Yan,
Khemraj Budachetri,
Libo Hou,
Ashweta Sahni,
Hongyan Liu,
NienChing Han,
Jeffrey Lakritz,
Dehua Pei,
Yasuko Rikihisa
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2024102118
Subject(s) - intracellular , effector , ehrlichia chaffeensis , biology , intracellular parasite , microbiology and biotechnology , ehrlichia , virology , tick
Significance Disease-relevant targets of infection by obligatory intracellular pathogens are beyond the reach of conventional antibodies. The neutralizing targets of intracellular pathogens in host cells are mostly unknown. The present study attempted to overcome these limitations with a combination of nanobodies, transfection, and a cell-permeable peptide delivery method to inhibit infection and determine inhibitory mechanisms.Ehrlichia chaffeensis uses the type IV secretion system to deliver bacterial effector Etf-1 to establish intracellular infection. Our study demonstrates that a nanobody can specifically block Etf-1 functions and thereby blockE. chaffeensis infection in cell culture and in a mouse model, suggesting that this approach can be developed as a therapeutic intervention for human monocytic ehrlichiosis and other diseases caused by intracellular infections.