FadA from Fusobacterium nucleatum utilizes both secreted and nonsecreted forms for functional oligomerization for attachment and invasion of host cells.
Fusobacterium nucleatum is a Gram-negative anaerobe associated with various human infections, including periodontal diseases and preterm birth. A novel FadA adhesin was recently identified for host-cell binding. It consists of 129 amino acid residues, with an 18-amino acid signal peptide. Expression of FadA in Escherichia coli enhanced bacterial binding to host epithelial and endothelial cells. In both E. coli and F. nucleatum, FadA exists in two forms, the intact pre-FadA and the secreted mature FadA (mFadA), with pre-FadA anchored in the inner membrane and mFadA secreted outside the bacteria. Pre-FadA and mFadA formed high M(r) complexes. When each form was purified to a single species, mFadA was soluble at neutral pH, whereas pre-FadA was insoluble. Pre-FadA became soluble when mixed with mFadA or under acidic pH. When fluorescence-labeled mFadA alone was added to the epithelial cells, no binding was detected. However, when mixed with nonlabeled pre-FadA, binding and invasion of mFadA into epithelial cells was observed. FadA is a unique bacterial adhesin/invasin in that it utilizes its own two forms for both structural and functional purposes. The pre-FadA-mFadA complex is probably anchored in the inner membrane and protrudes through the outer membrane. Internalization of the pre-FadA-mFadA ensures invasion of the bacteria into the host cells.
Xu
Minghua
M
Department of Periodontics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Yamada
Mitsunori
M
Li
Mei
M
Liu
Hongqi
H
Chen
Shu G
SG
Han
Yiping W
YW
D018829:Adhesins, Bacterial / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004847:Epithelial Cells / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D016967:Fusobacterium nucleatum / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D009061:Mouth Mucosa / Q000378:metabolism; D011485:Protein Binding; D011817:Rabbits
D018829:Adhesins, Bacterial