ArticlePloS one2015
Pseudomonas aeruginosa Uses Dihydrolipoamide Dehydrogenase (Lpd) to Bind to the Human Terminal Pathway Regulators Vitronectin and Clusterin to Inhibit Terminal Pathway Complement Attack.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
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- Bloodstream infections: mechanisms of pathogenesis and opportunities for intervention.Nature reviews. Microbiology · 2025Review
- Proteomic approach to identify host cell attachment proteins provides protective Pseudomonas aeruginosa vaccine antigen FtsZ.NPJ vaccines · 2024Article
- Recruitment of Vitronectin by Bacterial Pathogens: A Comprehensive Overview.Microorganisms · 2024Review
- Determinants of bacterial survival and proliferation in blood.FEMS microbiology reviews · 2024Review
- The secreted host-cell protein clusterin interacts with PmpD and promotesFrontiers in cellular and infection microbiology · 2024Article
- Mitochondrial Alpha-Keto Acid Dehydrogenase Complexes: Recent Developments on Structure and Function in Health and Disease.Sub-cellular biochemistry · 2024Review
- Outer membrane protein OMP76 ofVirulence · 2023Article
- Subversion of the Complement System by Pseudomonas aeruginosa.Journal of bacteriology · 2023Review
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- Microbial evasion of the complement system: a continuous and evolving story.Frontiers in immunology · 2023Review
- The pathogenesis of DLD-mediated cuproptosis induced spinal cord injury and its regulation on immune microenvironment.Frontiers in cellular neuroscience · 2023Article
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- Subversion of host cell signaling: The arsenal of Rickettsial species.Frontiers in cellular and infection microbiology · 2022Review
- Molecular Mechanisms Involved in Pseudomonas aeruginosa Bacteremia.Advances in experimental medicine and biology · 2022Review
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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.
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