Pseudomonas aeruginosa Uses Dihydrolipoamide Dehydrogenase (Lpd) to Bind to the Human Terminal Pathway Regulators Vitronectin and Clusterin to Inhibit Terminal Pathway Complement Attack.
Hallström, Teresia ; Uhde, Melanie ; Singh, Birendra LU ; Skerka, Christine ; Riesbeck, Kristian LU
and Zipfel, Peter F
(2015)
In PLoS ONE
10(9).
- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8042130
- author
- Hallström, Teresia
; Uhde, Melanie
; Singh, Birendra
LU
; Skerka, Christine
; Riesbeck, Kristian
LU
and Zipfel, Peter F
- organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 10
- issue
- 9
- article number
- e0137630
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- pmid:26368530
- wos:000361601100100
- scopus:84947460665
- pmid:26368530
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0137630
- language
- English
- LU publication?
- yes
- id
- f0f54f8c-db11-4e81-926a-818338882de1 (old id 8042130)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26368530?dopt=Abstract
- date added to LUP
- 2016-04-01 15:00:24
- date last changed
- 2022-02-19 21:58:53
@article{f0f54f8c-db11-4e81-926a-818338882de1,
abstract = {{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.}},
author = {{Hallström, Teresia and Uhde, Melanie and Singh, Birendra and Skerka, Christine and Riesbeck, Kristian and Zipfel, Peter F}},
issn = {{1932-6203}},
language = {{eng}},
number = {{9}},
publisher = {{Public Library of Science (PLoS)}},
series = {{PLoS ONE}},
title = {{Pseudomonas aeruginosa Uses Dihydrolipoamide Dehydrogenase (Lpd) to Bind to the Human Terminal Pathway Regulators Vitronectin and Clusterin to Inhibit Terminal Pathway Complement Attack.}},
url = {{http://dx.doi.org/10.1371/journal.pone.0137630}},
doi = {{10.1371/journal.pone.0137630}},
volume = {{10}},
year = {{2015}},
}