MARTX toxins as effector delivery platforms

• Published in: Pathogens and disease Vol. 73; no. 9; p. ftv092
• Main Authors: Gavin, Hannah E., Satchell, Karla J. F.
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.12.2015
• Subjects: Amino acids; Animals; Bacteria; Bacterial Toxins - genetics; Bacterial Toxins - metabolism; Cell membranes; Cytoskeleton; Cytosol; Cytotoxicity; Disruption; Genetics; Humans; Microorganisms; Minireview; Models, Biological; Models, Molecular; Protein Transport; Proteins; Secretion; Toxins; Translocation; Virulence; Virulence factors; Virulence Factors - metabolism; translocation; secretion; RTX; MARTX; effector; bacterial toxin; Vibrio
• ISSN: 2049-632X; 2049-632X
• DOI: 10.1093/femspd/ftv092

Bacteria frequently manipulate their host environment via delivery of microbial ‘effector’ proteins to the cytosol of eukaryotic cells. In the case of the multifunctional autoprocessing repeats-in-toxins (MARTX) toxin, this phenomenon is accomplished by a single, >3500 amino acid polypeptide that carries information for secretion, translocation, autoprocessing and effector activity. MARTX toxins are secreted from bacteria by dedicated Type I secretion systems. The released MARTX toxins form pores in target eukaryotic cell membranes for the delivery of up to five cytopathic effectors, each of which disrupts a key cellular process. Targeted cellular processes include modulation or modification of small GTPases, manipulation of host cell signaling and disruption of cytoskeletal integrity. More recently, MARTX toxins have been shown to be capable of heterologous protein translocation. Found across multiple bacterial species and genera—frequently in pathogens lacking Type 3 or Type 4 secretion systems—MARTX toxins in multiple cases function as virulence factors. Innovative research at the intersection of toxin biology and bacterial genetics continues to elucidate the intricacies of the toxin as well as the cytotoxic mechanisms of its diverse effector collection. This review examines the multifunctional autoprocessing RTX (MARTX) toxins of bacteria and their role in delivery of diverse effector proteins into eukaryotic cells.