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

RTX Toxins Ambush Immunity’s First Cellular Responders

by Laura C. Ristow and Rodney A. Welch *,†
Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, WI 53706, USA
*
Author to whom correspondence should be addressed.
The authors dedicate this review to the memory and accomplishments of Dr. Edward (Ned) Lally, who passed away 11 February 2019.
Toxins 2019, 11(12), 720; https://doi.org/10.3390/toxins11120720
Received: 29 October 2019 / Revised: 5 December 2019 / Accepted: 7 December 2019 / Published: 10 December 2019
(This article belongs to the Special Issue RTX Toxins)
The repeats-in-toxin (RTX) family represents a unique class of bacterial exoproteins. The first family members described were toxins from Gram-negative bacterial pathogens; however, additional members included exoproteins with diverse functions. Our review focuses on well-characterized RTX family toxins from Aggregatibacter actinomycetemcomitans (LtxA), Mannheimia haemolytica (LktA), Bordetella pertussis (CyaA), uropathogenic Escherichia coli (HlyA), and Actinobacillus pleuropneumoniae (ApxIIIA), as well as the studies that have honed in on a single host cell receptor for RTX toxin interactions, the β2 integrins. The β2 integrin family is composed of heterodimeric members with four unique alpha subunits and a single beta subunit. β2 integrins are only found on leukocytes, including neutrophils and monocytes, the first responders to inflammation following bacterial infection. The LtxA, LktA, HlyA, and ApxIIIA toxins target the shared beta subunit, thereby targeting all types of leukocytes. Specific β2 integrin family domains are required for the RTX toxin’s cytotoxic activity and are summarized here. Research examining the domains of the RTX toxins required for cytotoxic and hemolytic activity is also summarized. RTX toxins attack and kill phagocytic immune cells expressing a single integrin family, providing an obvious advantage to the pathogen. The critical question that remains, can the specificity of the RTX-β2 integrin interaction be therapeutically targeted? View Full-Text
Keywords: RTX (repeats-in-toxin) toxin family; β2 integrins; Gram-negative bacteria; virulence factor RTX (repeats-in-toxin) toxin family; β2 integrins; Gram-negative bacteria; virulence factor
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Ristow, L.C.; Welch, R.A. RTX Toxins Ambush Immunity’s First Cellular Responders. Toxins 2019, 11, 720.

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