Aggregatibacter actinomycetemcomitans Leukotoxin (LtxA; Leukothera®): Mechanisms of Action and Therapeutic Applications

Toxins (Basel). 2019 Aug 26;11(9):489. doi: 10.3390/toxins11090489.

Abstract

Aggregatibacter actinomycetemcomitans is an oral pathogen that produces the RTX toxin, leukotoxin (LtxA; Leukothera®). A. actinomycetemcomitans is strongly associated with the development of localized aggressive periodontitis. LtxA acts as a virulence factor for A. actinomycetemcomitans to subvert the host immune response by binding to the β2 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®) toxin therapy for the treatment of hematological malignancies and immune-mediated diseases.

Keywords: Aggregatibacter actinomycetemcomitans; RTX (repeats-in-toxin) toxin; cell death; leukotoxin (LtxA); lymphocyte function-associated antigen-1 (LFA-1); oral microbiology; toxin therapy; virulence factor; β2 integrins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aggregatibacter actinomycetemcomitans / metabolism*
  • Aggregatibacter actinomycetemcomitans / pathogenicity
  • Cell Membrane / drug effects
  • Cell Survival / drug effects
  • Endothelial Cells / drug effects
  • Endothelial Cells / pathology
  • Exotoxins / isolation & purification
  • Exotoxins / pharmacology*
  • Exotoxins / therapeutic use
  • Hematologic Neoplasms / drug therapy
  • Humans
  • Immune System Diseases / drug therapy
  • Leukocytes / drug effects
  • Leukocytes / pathology
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Mouth / microbiology
  • Protein Binding
  • Virulence Factors / isolation & purification
  • Virulence Factors / pharmacology*
  • Virulence Factors / therapeutic use

Substances

  • Exotoxins
  • Lymphocyte Function-Associated Antigen-1
  • Virulence Factors
  • leukotoxin