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Interaction between leukotoxin and Cu,Zn superoxide dismutase in Aggregatibacter actinomycetemcomitans. 2007

Nataliya V Balashova, and Diane H Park, and Jigna K Patel, and David H Figurski, and Scott C Kachlany
Department of Oral Biology, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.

Aggregatibacter (Actinobacillus) actinomycetemcomitans is a gram-negative oral pathogen that is the etiologic agent of localized aggressive periodontitis and systemic infections. A. actinomycetemcomitans produces leukotoxin (LtxA), which is a member of the RTX (repeats in toxin) family of secreted bacterial toxins and is known to target human leukocytes and erythrocytes. To better understand how LtxA functions as a virulence factor, we sought to detect and study potential A. actinomycetemcomitans proteins that interact with LtxA. We found that Cu,Zn superoxide dismutase (SOD) interacts specifically with LtxA. Cu,Zn SOD was purified from A. actinomycetemcomitans to homogeneity and remained enzymatically active. Purified Cu,Zn SOD allowed us to isolate highly specific anti-Cu,Zn SOD antibody and this antibody was used to further confirm protein interaction. Cu,Zn SOD-deficient mutants displayed decreased survival in the presence of reactive oxygen and nitrogen species and could be complemented with wild-type Cu,Zn SOD in trans. We suggest that A. actinomycetemcomitans Cu,Zn SOD may protect both bacteria and LtxA from reactive species produced by host inflammatory cells during disease. This is the first example of a protein-protein interaction involving a bacterial Cu,Zn SOD.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D005098 Exotoxins Toxins produced, especially by bacterial or fungal cells, and released into the culture medium or environment. Exotoxin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013482 Superoxide Dismutase An oxidoreductase that catalyzes the reaction between SUPEROXIDES and hydrogen to yield molecular oxygen and hydrogen peroxide. The enzyme protects the cell against dangerous levels of superoxide. Hemocuprein,Ag-Zn Superoxide Dismutase,Cobalt Superoxide Dismutase,Cu-Superoxide Dismutase,Erythrocuprein,Fe-Superoxide Dismutase,Fe-Zn Superoxide Dismutase,Iron Superoxide Dismutase,Manganese Superoxide Dismutase,Mn-SOD,Mn-Superoxide Dismutase,Ag Zn Superoxide Dismutase,Cu Superoxide Dismutase,Dismutase, Ag-Zn Superoxide,Dismutase, Cobalt Superoxide,Dismutase, Cu-Superoxide,Dismutase, Fe-Superoxide,Dismutase, Fe-Zn Superoxide,Dismutase, Iron Superoxide,Dismutase, Manganese Superoxide,Dismutase, Mn-Superoxide,Dismutase, Superoxide,Fe Superoxide Dismutase,Fe Zn Superoxide Dismutase,Mn SOD,Mn Superoxide Dismutase,Superoxide Dismutase, Ag-Zn,Superoxide Dismutase, Cobalt,Superoxide Dismutase, Fe-Zn,Superoxide Dismutase, Iron,Superoxide Dismutase, Manganese
D016976 Aggregatibacter actinomycetemcomitans A species of Gram-negative, facultatively anaerobic spherical or rod-shaped bacteria indigenous to dental surfaces. It is associated with PERIODONTITIS; BACTERIAL ENDOCARDITIS; and ACTINOMYCOSIS. Actinobacillus actinomycetemcomitans,Bacterium acetinomycetum comitans,Bacterium comitans,Haemophilus actinomyceticomitans,Haemophilus actinomycetemcomitans
D017382 Reactive Oxygen Species Molecules or ions formed by the incomplete one-electron reduction of oxygen. These reactive oxygen intermediates include SINGLET OXYGEN; SUPEROXIDES; PEROXIDES; HYDROXYL RADICAL; and HYPOCHLOROUS ACID. They contribute to the microbicidal activity of PHAGOCYTES, regulation of SIGNAL TRANSDUCTION and GENE EXPRESSION, and the oxidative damage to NUCLEIC ACIDS; PROTEINS; and LIPIDS. Active Oxygen Species,Oxygen Radical,Oxygen Radicals,Pro-Oxidant,Reactive Oxygen Intermediates,Active Oxygen,Oxygen Species, Reactive,Pro-Oxidants,Oxygen, Active,Pro Oxidant,Pro Oxidants,Radical, Oxygen
D018922 HL-60 Cells A promyelocytic cell line derived from a patient with ACUTE PROMYELOCYTIC LEUKEMIA. HL-60 cells lack specific markers for LYMPHOID CELLS but express surface receptors for FC FRAGMENTS and COMPLEMENT SYSTEM PROTEINS. They also exhibit phagocytic activity and responsiveness to chemotactic stimuli. (From Hay et al., American Type Culture Collection, 7th ed, pp127-8) HL60 Cells,Cell, HL60,Cells, HL60,HL 60 Cells,HL-60 Cell,HL60 Cell
D037521 Virulence Factors Those components of an organism that determine its capacity to cause disease but are not required for its viability per se. Two classes have been characterized: TOXINS, BIOLOGICAL and surface adhesion molecules that effect the ability of the microorganism to invade and colonize a host. (From Davis et al., Microbiology, 4th ed. p486) Pathogenicity Factor,Pathogenicity Factors,Virulence Factor,Factor, Pathogenicity,Factor, Virulence,Factors, Pathogenicity,Factors, Virulence

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