Multifunctional-autoprocessing repeats-in-toxin (MARTX) Toxins of Vibrios

Abstract

Multifunctional-autoprocessing repeats-in-toxin (MARTX) toxins are a heterogeneous group of toxins found in a number of Vibrio species and other Gram-negative bacteria. The toxins are composed of conserved repeat regions and an autoprocessing protease domain that together function as a delivery platform for transfer of cytotoxic and cytopathic domains into target eukaryotic cell cytosol. Within the cells, the effectors can alter biological processes such as signaling or cytoskeletal structure, presumably to the benefit of the bacterium. Ten effector domains are found in the various Vibrio MARTX toxins, although any one toxin carries only two to five effector domains. The specific toxin variant expressed by a species can be modified by homologous recombination to acquire or lose effector domains, such that different strains within the same species can express distinct variants of the toxins. This review examines the conserved structural elements of the MARTX toxins and details the different toxin arrangements carried by Vibrio species and strains. The catalytic function of domains and how the toxins are linked to pathogenesis of human and animals is described.

FIGURE 1

The multifunctional-autoprocessing repeats-in-toxin (MARTX) toxins are a form of effector delivery similar in concept to contact-dependent type III secretion and type IV secretion. The major difference is that the toxin is secreted from the bacterium by type I secretion and then the large single polypeptide toxin delivers effectors directly across the plasma membrane with delivery occurring by polypeptide autoprocessing. Similar to type III and type IV secretion, the effector themselves confer cytopathic and cytotoxic activities that then alter host-cell biology to the benefit of the bacterium. doi:10.1128/microbiolspec.VE-0002-2014.f1

FIGURE 2

(A) The general structure of a multifunctional-autoprocessing repeats-in-toxin (MARTX) toxin showing the number and position of various repeat sequences, auto-processing cysteine protease domain (CPD), and variable region containing the effector domains. The secretion signal (s.s.) is shown at the extreme C-terminus. (B) Graphical representation of the different repeat sequences generated by Weblogo 2.8.2 [(113); weblogo.berkeley.edu]. The sequences used were repeat sequences from Vibrio vulnificus CMCP6 identified based on the alignment of sequence to the repeat annotation of V. cholerae (1). The portion of the C-repeat that aligns to the calcium-binding beta roll nonapeptide repeat of other RTX family proteins is indicated. Note conservation of a G-7x–G-4x–N repeat in all of the repeats. doi:10.1128/microbiolspec.VE-0002-2014.f2

FIGURE 3

Schematic representation of all multifunctional-autoprocessing repeats-in-toxin (MARTX) toxins described in text. Toxins are identified by species at left with representative strain isolate designation at the right. BT2 and BT3 refer to Vibrio vulnificus biotype 2 and 3, respectively, and Vnig_pA refers to the large pA1066 plasmid of V. nigripulchritudo. Legend for different domains is at the bottom. All amino acid sequences are from published papers referenced in the text and the sequences were downloaded from the NCBI website (www.ncbi.nlm.nih.gov). All effector domain arrangements are as annotated previously (1, 11, 29, 34, 35, 63) except for new sequences done specifically for this article, including V. vulnificus JY1701, V. anguillarum 775 and 96F, V. ordalli 33509, and V. splendidus 5S-101. doi:10.1128/microbiolspec.VE-0002-2014.f3