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Microbial Toxins pp 1–29Cite as

RTX Toxins: A Review

  • Living reference work entry
  • First Online:

Part of the book series: Toxinology ((TOXI))

Abstract

Repeats-in-toxin (RTX) exoproteins of Gram-negative bacteria form a steadily growing family of proteins with diverse biological functions. All the diverse RTX toxins share two common features: (i) they are secreted by a single-step export mechanism via the type I secretion system that employs a “channel–tunnel” conduit spanning across the entire Gram-negative bacterial envelope, thus connecting bacterial cytoplasm to extracellular environment; (ii) RTX toxins possess the characteristic glycine- and aspartate-rich repeats that bind numerous calcium ions, typically in the carboxy-terminal portions of the molecule, with the large multifunctional autoprocessing RTX (MARTX) toxins bearing similar repeats also as N-terminal segments. RTX toxins further require physiologically high (>1 mM) Ca2+ concentration for proper folding and biological activity on host epithelial or phagocytic cells. Members of the RTX family of toxins act as effective “contact weapons” and have been shown to play a major role in virulence of a broad range of Gram-negative pathogens.

The classical RTX toxins, originally classified as leukotoxins and hemolysins, were shown to penetrate and permeabilize host cell membranes. Research over the past decade, however, revealed that RTX toxins can exert numerous additional activities contributing to cytotoxic action in pathogenesis and virulence of bacterial infections. Some of the RTX toxins affect host cell signaling via uncontrolled conversion of ATP to a key signaling molecule, cAMP (CyaA, MARTXVc), or via interaction with small GTPases (MARTXVc, MARTXVv) and thus effectively subvert host cell physiology. Other RTX toxins induce cytoskeletal rearrangements via covalent cross-linking of actin molecules (MARTXVc, MARTXVv), or inflict an apoptotic/lytic program on target phagocytic or epithelial cells (HlyA, CyaA, MARTXVv), thereby promoting disease pathogenesis.

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Acknowledgments

This work was supported by Grants No. GAP302/11/0580, GA13-14547S, GA15-09157S, GAP302/12/0460, and GA15-11851S from the Czech Science Foundation and by the Institutional Research Project RVO 61388971 of the Institute of Microbiology.

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  1. Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology of the ASCR, v.v.i.,, Videnska 1083, 142 20, Prague 4, Czech Republic

    Irena Linhartova, Radim Osicka, Ladislav Bumba, Jiri Masin & Peter Sebo

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  1. Irena Linhartova
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  1. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    P. Gopalakrishnakone

  2. Biology Department, Wilson College , Chambersburg, Pennsylvania, USA

    Brad Stiles

  3. Department of Biochemistry, School of Medicine and Instituto Clodomiro Picado, Faculty of Microbiology, University of Costa Rica , San Pedro de Montes de Oca, Costa Rica

    Alberto Alape-Girón

  4. Département de pathologie et microbiologie, Faculté de médecine vétérinaire, Université de Montréal , Saint-Hyacinthe, Canada

    J. Daniel Dubreuil

  5. College of Pharmacy, Roseman University of Health Sciences, Henderson, Nevada, USA

    Manas Mandal

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Linhartova, I., Osicka, R., Bumba, L., Masin, J., Sebo, P. (2015). RTX Toxins: A Review. In: Gopalakrishnakone, P., Stiles, B., Alape-Girón, A., Dubreuil, J., Mandal, M. (eds) Microbial Toxins. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6725-6_13-1

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