RTX Toxins of Animal Pathogens and Their Role as Antigens in Vaccines and Diagnostics

Abstract

Exotoxins play a central role in the pathologies caused by most major bacterial animal pathogens. The large variety of vertebrate and invertebrate hosts in the animal kingdom is reflected by a large variety of bacterial pathogens and toxins. The group of repeats in the structural toxin (RTX) toxins is particularly abundant among bacterial pathogens of animals. Many of these toxins are described as hemolysins due to their capacity to lyse erythrocytes in vitro. Hemolysis by RTX toxins is due to the formation of cation-selective pores in the cell membrane and serves as an important marker for virulence in bacterial diagnostics. However, their physiologic relevant targets are leukocytes expressing β2 integrins, which act as specific receptors for RTX toxins. For various RTX toxins, the binding to the CD18 moiety of β2 integrins has been shown to be host specific, reflecting the molecular basis of the host range of RTX toxins expressed by bacterial pathogens. Due to the key role of RTX toxins in the pathogenesis of many bacteria, antibodies directed against specific RTX toxins protect against disease, hence, making RTX toxins valuable targets in vaccine research and development. Due to their specificity, several structural genes encoding for RTX toxins have proven to be essential in modern diagnostic applications in veterinary medicine.

MALDI-TOF MS Biomarker Detection Models to Distinguish RTX Toxin Phenotypes of Moraxella bovoculi Strains Are Enhanced Using Calcium Chloride Supplemented Agar

“…RTX toxins are known virulence factors in a variety of veterinary pathogens, including species within the family Pasteurellacea ( Linhartova et al, 2018 ). A well-studied example of this is the leukotoxin produced by Mannheimia haemolytica ( Frey, 2019 ). These RTX toxins are secreted in a calcium-dependent manner via a type I secretion system (T1SS) responsible for translocating the toxin from the cytosol to the exterior ( Linhartova et al, 2018 ) Like M. bovis , some M. bovoculi strains also contain a complete RTX operon that produces an RTX toxin, cytotoxin A encoded by mbvA ( Angelos et al, 2007a ).…”

RTX-Toxins

“…LtxA (trade name Leukothera ® ) may provide therapeutic applications for the treatment of hematological malignancies and immune-mediated diseases [18]. All of the mentioned cytolysins form cation-selective pores in the cell membranes as the primary event [16][17][18]20,21,24,25]. This means that antibodies directed against specific RTX toxins could protect from diseases [21].…”

“…All of the mentioned cytolysins form cation-selective pores in the cell membranes as the primary event [16][17][18]20,21,24,25]. This means that antibodies directed against specific RTX toxins could protect from diseases [21]. RTX toxins could, therefore, serve as antigens for vaccine research and development to treat the corresponding bacterial diseases [20][21][22].…”

“…This means that antibodies directed against specific RTX toxins could protect from diseases [21]. RTX toxins could, therefore, serve as antigens for vaccine research and development to treat the corresponding bacterial diseases [20][21][22]. These considerations are important for diagnostic applications in human and veterinary medicine, as outlined in three contributions in this Special Issue [18,21,22].…”

“…This Special Issue focuses on the function of RTX toxins of different subfamilies and their role in disease [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ]. Of special interest is the structure of the nonapeptide repeats and their interaction with calcium ions, which represents some prerequisites for target cell recognition [ 13 ].…”