<i>Aggregatibacter actinomycetemcomitans</i> Leukotoxin (LtxA; Leukothera^®): Mechanisms of Action and Therapeutic Applications

• Main Authors: Brian A. Vega, Benjamin A. Belinka Jr., Scott C. Kachlany
• Format: Article
• Language: English
• Published: MDPI AG 2019-08-01
• Series: Toxins
• Subjects: leukotoxin (LtxA); RTX (repeats-in-toxin) toxin; <i>Aggregatibacter actinomycetemcomitans</i>; lymphocyte function-associated antigen-1 (LFA-1); β₂ integrins; cell death; oral microbiology; virulence factor; toxin therapy
• Online Access: https://www.mdpi.com/2072-6651/11/9/489

<i>Aggregatibacter actinomycetemcomitans</i> is an oral pathogen that produces the RTX toxin, leukotoxin (LtxA; Leukothera^&#174;). <i>A. actinomycetemcomitans</i> is strongly associated with the development of localized aggressive periodontitis. LtxA acts as a virulence factor for <i>A. actinomycetemcomitans</i> to subvert the host immune response by binding to the &#946;₂ integrin lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) on white blood cells (WBCs), causing cell death. In this paper, we reviewed the state of knowledge on LtxA interaction with WBCs and the subsequent mechanisms of induced cell death. Finally, we touched on the potential therapeutic applications of LtxA (trade name Leukothera^&#174;) toxin therapy for the treatment of hematological malignancies and immune-mediated diseases.