{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T21:30:50Z","timestamp":1774128650639,"version":"3.50.1"},"reference-count":45,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2010,12,14]],"date-time":"2010-12-14T00:00:00Z","timestamp":1292284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Aggregatibacter actinomycetemcomitans is an oral pathogen and etiologic agent of localized aggressive periodontitis. The bacterium is also a cardiovascular pathogen causing infective endocarditis. A. actinomycetemcomitans produces leukotoxin (LtxA), an important virulence factor that targets white blood cells (WBCs) and plays a role in immune evasion during disease. The functional receptor for LtxA on WBCs is leukocyte function antigen-1 (LFA-1), a b-2 integrin that is modified with N-linked carbohydrates. Interaction between toxin and receptor leads to cell death. We recently discovered that LtxA can also lyse red blood cells (RBCs) and hemolysis may be important for pathogenesis of A. actinomycetemcomitans. In this study, we further investigated how LtxA might recognize and lyse RBCs. We found that, in contrast to a related toxin, E. coli a-hemolysin, LtxA does not recognize glycophorin on RBCs. However, gangliosides were able to completely block LtxA-mediated hemolysis. Furthermore, LtxA did not show a preference for any individual ganglioside. LtxA also bound to ganglioside-rich C6 rat glioma cells, but did not kill them. Interaction between LtxA and C6 cells could be blocked by gangliosides with no apparent specificity. Gangliosides were only partially effective at preventing LtxA-mediated cytotoxicity of WBCs, and the effect was only observed when a high ratio of ganglioside:LtxA was used over a short incubation period. Based on the results presented here, we suggest that because of the similarity between N-linked sugars on LFA-1 and the structures of gangliosides, LtxA may have acquired the ability to lyse RBCs.<\/jats:p>","DOI":"10.3390\/toxins2122824","type":"journal-article","created":{"date-parts":[[2010,12,14]],"date-time":"2010-12-14T13:26:35Z","timestamp":1292333195000},"page":"2824-2836","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Gangliosides Block Aggregatibacter Actinomycetemcomitans Leukotoxin (LtxA)-Mediated Hemolysis"],"prefix":"10.3390","volume":"2","author":[{"given":"Michael S.","family":"Forman","sequence":"first","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jason B.","family":"Nishikubo","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca K.","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amy","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nataliya V.","family":"Balashova","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Scott C.","family":"Kachlany","sequence":"additional","affiliation":[{"name":"Department of Oral Biology, New Jersey Dental School, University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07103, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2010,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1111\/j.1600-0757.2006.00189.x","article-title":"How we got attached to Actinobacillus actinomycetemcomitans: A model for infectious diseases","volume":"42","author":"Fine","year":"2006","journal-title":"Periodontol 2000"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/j.1600-0757.1999.tb00159.x","article-title":"Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in human periodontal disease: Occurrence and treatment","volume":"20","author":"Slots","year":"1999","journal-title":"Periodontol 2000"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1600-051X.1985.tb01348.x","article-title":"Actinobacillus actinomycetemcomitans in human periodontal disease","volume":"12","author":"Zambon","year":"1985","journal-title":"J. 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