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2015 ; 10
(9
): e0137630
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Pseudomonas aeruginosa Uses Dihydrolipoamide Dehydrogenase (Lpd) to Bind to the
Human Terminal Pathway Regulators Vitronectin and Clusterin to Inhibit Terminal
Pathway Complement Attack
#MMPMID26368530
Hallström T
; Uhde M
; Singh B
; Skerka C
; Riesbeck K
; Zipfel PF
PLoS One
2015[]; 10
(9
): e0137630
PMID26368530
show ga
The opportunistic human pathogen Pseudomonas aeruginosa controls host innate
immune and complement attack. Here we identify Dihydrolipoamide dehydrogenase
(Lpd), a 57 kDa moonlighting protein, as the first P. aeruginosa protein that
binds the two human terminal pathway inhibitors vitronectin and clusterin. Both
human regulators when bound to the bacterium inhibited effector function of the
terminal complement, blocked C5b-9 deposition and protected the bacterium from
complement damage. P. aeruginosa when challenged with complement active human
serum depleted from vitronectin was severely damaged and bacterial survival was
reduced by over 50%. Similarly, when in human serum clusterin was blocked by a
mAb, bacterial survival was reduced by 44%. Thus, demonstrating that Pseudomonas
benefits from attachment of each human regulator and controls complement attack.
The Lpd binding site in vitronectin was localized to the C-terminal region, i.e.
to residues 354-363. Thus, Lpd of P. aeruginosa is a surface exposed moonlighting
protein that binds two human terminal pathway inhibitors, vitronectin and
clusterin and each human inhibitor when attached protected the bacterial pathogen
from the action of the terminal complement pathway. Our results showed insights
into the important function of Lpd as a complement regulator binding protein that
might play an important role in virulence of P. aeruginosa.