Structure and mode of action of RTX toxins

Ludwig, Albrecht; Goebel, Werner

doi:10.1016/b978-012088445-2/50034-2

Cited by 8 publications

(8 citation statements)

References 272 publications

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“…Below, we provide a basic overview of the biochemical and genetic features of HlyA, highlighting recent progress in addressing two key questions concerning HlyA biology: what dictates target cell specificity and what is the structural nature of the HlyA pore? For further discussion on these topics, the reader is referred to Iacovache et al, Linhartová et al, Welch, Frey and Ludwig and Goebel [1,2,5,27,28]. …”

Section: α-Hemolysin: a Prototype Rtx Toxinmentioning

confidence: 99%

“…Indeed, alignments between phylogenetically distributed RTX toxins indicate that contemporary UPEC hemolysin genes originated from the bacterial lineage Pasteurellaceae , which includes several opportunistic animal pathogens [45–48]. Although a number of these evolutionarily related HlyA-like toxins share many biochemical and genetic characteristics, they also exhibit unique properties that include differences in target cell and host range specificities, pore structure and the potential to elicit particular cellular responses [5,28,49,50]. …”

Section: α-Hemolysin: a Prototype Rtx Toxinmentioning

confidence: 99%

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The RTX Pore-Forming Toxin α-Hemolysin of Uropathogenic Escherichia Coli : Progress and Perspectives

Wiles

Mulvey

2012

Future Microbiol.

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Members of the RTX family of protein toxins are functionally conserved among an assortment of bacterial pathogens. By disrupting host cell integrity through their pore-forming and cytolytic activities, this class of toxins allows pathogens to effectively tamper with normal host cell processes, promoting pathogenesis. Here, we focus on the biology of RTX toxins by describing salient properties of a prototype member, α-hemolysin, which is of ten encoded by strains of uropathogenic Escherichia coli. It has long been appreciated that RTX toxins can have distinct effects on host cells aside from outright lysis. Recently, advances in modeling and analysis of host–pathogen interactions have led to novel findings concerning the consequences of pore formation during host–pathogen interactions. We discuss current progress on longstanding questions concerning cell specificity and pore formation, new areas of investigation that involve toxin-mediated perturbations of host cell signaling cascades and perspectives on the future of RTX toxin investigation.

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Section: α-Hemolysin: a Prototype Rtx Toxinmentioning

confidence: 99%

Section: α-Hemolysin: a Prototype Rtx Toxinmentioning

confidence: 99%

The RTX Pore-Forming Toxin α-Hemolysin of Uropathogenic Escherichia Coli : Progress and Perspectives

Wiles

Mulvey

2012

Future Microbiol.

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“…HlyB recognizes the secretion signal of HlyA, and, in addition, binds and hydrolyses ATP through its C-terminal domain, which is necessary for the export process. HlyD permits HlyA to contact the TolC pore in the outer membrane, which mediates its transport into the external medium (Oxhamre and Richter-Dahlfors, 2003;Ludwig and Goebel, 2006).…”

Section: Toxin Activation By Lipid Posttranslational Modification (Rtmentioning

confidence: 99%

“…Structural changes in the Ca 2+ -binding domain probably induce a more intimate binding to the membrane. Re-orientation of the fatty acids would permit the insertion of a part of the toxin into the lipid bilayer, resulting in a pore formation (Oxhamre and Richter-Dahlfors, 2003;Ludwig and Goebel, 2006). ShlA (Serratia marcescens haemolysin) and related haemolysins are also activated by phospholipids.…”

Section: Toxin Activation By Lipid Posttranslational Modification (Rtmentioning

confidence: 99%

Bacterial protein toxins and lipids: role in toxin targeting and activity

Geny

Popoff

2006

Biology of the Cell

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All bacterial toxins, which globally are hydrophilic proteins, interact first with their target cells by recognizing a surface receptor, which is either a lipid or a lipid derivative, or another compound but in a lipid environment. Intracellular active toxins follow various trafficking pathways, the sorting of which is greatly dependent on the nature of the receptor, notably lipidic receptor or receptor embedded into a distinct environment such as lipid microdomains. Numerous other toxins act locally on cell membrane. Indeed, phospholipase activity is a common mechanism shared by several membrane‐damaging toxins. In addition, many toxins active intracellularly or on cell membrane modulate host cell phospholipid pathways. Unusually, a few bacterial toxins require a lipid post‐translational modification to be active. Thereby, lipids are obligate partners of bacterial toxins.

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“…LtxA is a member of the repeats‐in‐toxin (RTX) family of proteins (Ludwig & Goebel, 2006). This family shares a number of structural and functional features, including synthesis of four essential proteins from genes organized into a single operon ( rtxCABD , in transcriptional order; Ludwig & Goebel, 2006). These genes encode for the structural protein ( rtxA ), an acyltransferase ( rtxC ), and two proteins that are essential components of the secretion machinery ( rtxB and rtxD ).…”

Section: Ltxa Expression/secretionmentioning

confidence: 99%

Aggregatibacter actinomycetemcomitans leukotoxin: From mechanism to targeted anti‐toxin therapeutics

Krueger

Brown

2020

Molecular Oral Microbiology

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Aggregatibacter actinomycetemcomitans is a Gram-negative bacterium associated with localized aggressive periodontitis, as well as other systemic diseases. This organism produces a number of virulence factors, all of which provide some advantage to the bacterium. Several studies have demonstrated that clinical isolates from diseased patients, particularly those of African descent, frequently belong to specific clones of A. actinomycetemcomitans that produce significantly higher amounts of a protein exotoxin belonging to the repeats-in-toxin (RTX) family, leukotoxin (LtxA), whereas isolates from healthy patients harbor minimally leukotoxic strains. This finding suggests that LtxA might play a key role in A. actinomycetemcomitans pathogenicity. Because of this correlation, much work over the past 30 years has been focused on understanding the mechanisms by which LtxA interacts with and kills host cells.In this article, we review those findings, highlight the remaining open questions, and demonstrate how knowledge of these mechanisms, particularly the toxin's interactions with lymphocyte function-associated antigen-1 (LFA-1) and cholesterol, enables the design of targeted anti-LtxA strategies to prevent/treat disease. K E Y W O R D SAggregatibacter actinomycetemcomitans, leukotoxin, LFA-1, repeats-in-toxin

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Structure and mode of action of RTX toxins

Cited by 8 publications

References 272 publications

The RTX Pore-Forming Toxin α-Hemolysin of Uropathogenic Escherichia Coli : Progress and Perspectives

The RTX Pore-Forming Toxin α-Hemolysin of Uropathogenic Escherichia Coli : Progress and Perspectives

Bacterial protein toxins and lipids: role in toxin targeting and activity

Aggregatibacter actinomycetemcomitans leukotoxin: From mechanism to targeted anti‐toxin therapeutics

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