title: Interaction between leukotoxin and Cu,Zn superoxide dismutase in Aggregatibacter actinomycetemcomitans.
abstract: 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.
authors.affiliation: Department of Oral Biology, University of Medicine and Dentistry of New Jersey, Newark, NJ 07103, USA.
authors.forename: Nataliya V
authors.initials: NV
authors.lastname: Balashova
authors.forename: Diane H
authors.initials: DH
authors.lastname: Park
authors.forename: Jigna K
authors.initials: JK
authors.lastname: Patel
authors.forename: David H
authors.initials: DH
authors.lastname: Figurski
authors.forename: Scott C
authors.initials: SC
authors.lastname: Kachlany
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000201:enzymology* / Q000472:pathogenicity; D005098:Exotoxins / Q000378:metabolism* / Q000502:physiology; D018922:HL-60 Cells; D006801:Humans; D007249:Inflammation / Q000201:enzymology / Q000378:metabolism / Q000382:microbiology; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000633:toxicity; D013482:Superoxide Dismutase / Q000302:isolation & purification / Q000378:metabolism* / Q000502:physiology; D037521:Virulence Factors / Q000378:metabolism / Q000502:physiology
chemical_list: D005098:Exotoxins; D017382:Reactive Oxygen Species; D037521:Virulence Factors; C018579:leukotoxin; D013482:Superoxide Dismutase