Rho-modifying bacterial protein toxins from Photorhabdus species

Jank, Thomas; Lang, Alexander E.; Aktories, Klaus

doi:10.1016/j.toxicon.2015.05.017

Cited by 5 publications

(6 citation statements)

References 59 publications

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“…The TcA and TcB components form the secretion/delivery system, whilst the TcC component generally carries the toxin activity [52]. The TcC gene can be present in different isoforms with different activities and/or targets [53]. For example, whilst both TccC3 and TccC5 induce actin polymerization, TccC3 has ADPribosyltransferase activity against actin at Thr148, whilst TccC5 is an ADP-ribosyltransferase that targets Rho proteins at Gln61/63, resulting in constitutive activation of these small GTPases [47,53,54].…”

Section: Family 1: the Tc Toxinsmentioning

confidence: 99%

“…The TcC gene can be present in different isoforms with different activities and/or targets [53]. For example, whilst both TccC3 and TccC5 induce actin polymerization, TccC3 has ADPribosyltransferase activity against actin at Thr148, whilst TccC5 is an ADP-ribosyltransferase that targets Rho proteins at Gln61/63, resulting in constitutive activation of these small GTPases [47,53,54]. Both TccC3 and TccC5 toxins can also affect transcription in the target cells by modifying the activity of the MAL and AP1 transcription factors [55].…”

Section: Family 1: the Tc Toxinsmentioning

confidence: 99%

“…These include the PirAB binary toxin that has been shown to have oral and injectable activity against moth and mosquito larvae [72][73][74]. In addition, the PaTox toxin, originally described in P. asymbiotica, has been shown to have glycosyltransferase and deamidase activity that targets host Rho and G proteins, respectively, resulting in apoptosis of target cells [53,[75][76][77].…”

Section: Family 2: Mcf Toxinmentioning

confidence: 99%

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Photorhabdus: a tale of contrasting interactions

Clarke

2020

Microbiology

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Different model systems have, over the years, contributed to our current understanding of the molecular mechanisms underpinning the various types of interaction between bacteria and their animal hosts. The genus Photorhabdus comprises Gram-negative insect pathogenic bacteria that are normally found as symbionts that colonize the gut of the infective juvenile stage of soil-dwelling nematodes from the family Heterorhabditis. The nematodes infect susceptible insects and release the bacteria into the insect haemolymph where the bacteria grow, resulting in the death of the insect. At this stage the nematodes feed on the bacterial biomass and, following several rounds of reproduction, the nematodes develop into infective juveniles that leave the insect cadaver in search of new hosts. Therefore Photorhabdus has three distinct and obligate roles to play during this life-cycle: (1) Photorhabdus must kill the insect host; (2) Photorhabdus must be capable of supporting nematode growth and development; and (3) Photorhabdus must be able to colonize the gut of the next generation of infective juveniles before they leave the insect cadaver. In this review I will discuss how genetic analysis has identified key genes involved in mediating, and regulating, the interaction between Photorhabdus and each of its invertebrate hosts. These studies have resulted in the characterization of several new families of toxins and a novel inter-kingdom signalling molecule and have also uncovered an important role for phase variation in the regulation of these different roles.

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Section: Family 1: the Tc Toxinsmentioning

confidence: 99%

Section: Family 1: the Tc Toxinsmentioning

confidence: 99%

Section: Family 2: Mcf Toxinmentioning

confidence: 99%

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Photorhabdus: a tale of contrasting interactions

Clarke

2020

Microbiology

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“…Post-translational modification of host proteins by sugar attachment, known as glycosylation, and accomplished by bacterial glycosyltransferases (GTs) ( Figure 1 A), has attracted much attention after the pioneering studies of K. Aktories and M. Popoff on secreted Clostridioides difficile cytotoxins ( Table 1 ) [ 30 ]. In the following years, the list of bacterial glycosyltransferase virulence factors grew considerably due to the discovery of additional toxins of Clostridia , Photorhabdus , Yersinia , Chlamydia , and Escherichia coli [ 31 , 32 ]. Seminal work guided by K. Aktories and M. Popoff on L. pneumophila led to the identification of the first T4BSS glucosylating effector Lgt1 [ 33 , 34 ].…”

Section: Introductionmentioning

confidence: 99%

Glycosylating Effectors of Legionella pneumophila: Finding the Sweet Spots for Host Cell Subversion

Belyi

Levanova²,

Schroeder

2022

Biomolecules

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Work over the past two decades clearly defined a significant role of glycosyltransferase effectors in the infection strategy of the Gram-negative, respiratory pathogen Legionella pneumophila. Identification of the glucosyltransferase effectors Lgt1-3, specifically modifying elongation factor eEF1A, disclosed a novel mechanism of host protein synthesis manipulation by pathogens and illuminated its impact on the physiological state of the target cell, in particular cell cycle progression and immune and stress responses. Recent characterization of SetA as a general O-glucosyltransferase with a wide range of targets including the proteins Rab1 and Snx1, mediators of membrane transport processes, and the discovery of new types of glycosyltransferases such as LtpM and SidI indicate that the vast effector arsenal might still hold more so-far unrecognized family members with new catalytic features and substrates. In this article, we review our current knowledge regarding these fascinating biomolecules and discuss their role in introducing new or overriding endogenous post-translational regulatory mechanisms enabling the subversion of eukaryotic cells by L. pneumophila.

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“…Another type of toxin system consists of several large multidomain components that collectively make a pore in the membrane, attach to a target cell, and then deliver and cleave the toxin domain off once inside the target cell. These systems are typified by entomotoxins TcABC (toxin complex ABC) from Photorhabdus species that target eukaryotic cells via modification of Rho GTPases (3,12). Some toxins are secreted outside the cell through dedicated secretion systems that either recognize specific signal sequences or use dedicated chaperones to target these toxins for export (9).…”

mentioning

confidence: 99%

Antimicrobial Peptides, Polymorphic Toxins, and Self-Nonself Recognition Systems in Archaea: an Untapped Armory for Intermicrobial Conflicts

Makarova

Wolf

Karamycheva

et al. 2019

mBio

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Numerous, diverse, highly variable defense and offense genetic systems are encoded in most bacterial genomes and are involved in various forms of conflict among competing microbes or their eukaryotic hosts. Here we focus on the offense and self-versus-nonself discrimination systems encoded by archaeal genomes that so far have remained largely uncharacterized and unannotated. Specifically, we analyze archaeal genomic loci encoding polymorphic and related toxin systems and ribosomally synthesized antimicrobial peptides. Using sensitive methods for sequence comparison and the “guilt by association” approach, we identified such systems in 141 archaeal genomes. These toxins can be classified into four major groups based on the structure of the components involved in the toxin delivery. The toxin domains are often shared between and within each system. We revisit halocin families and substantially expand the halocin C8 family, which was identified in diverse archaeal genomes and also certain bacteria. Finally, we employ features of protein sequences and genomic locus organization characteristic of archaeocins and polymorphic toxins to identify candidates for analogous but not necessarily homologous systems among uncharacterized protein families. This work confidently predicts that more than 1,600 archaeal proteins, currently annotated as “hypothetical” in public databases, are components of conflict and self-versus-nonself discrimination systems. IMPORTANCE Diverse and highly variable systems involved in biological conflicts and self-versus-nonself discrimination are ubiquitous in bacteria but much less studied in archaea. We performed comprehensive comparative genomic analyses of the archaeal systems that share components with analogous bacterial systems and propose an approach to identify new systems that could be involved in these functions. We predict polymorphic toxin systems in 141 archaeal genomes and identify new, archaea-specific toxin and immunity protein families. These systems are widely represented in archaea and are predicted to play major roles in interactions between species and in intermicrobial conflicts. This work is expected to stimulate experimental research to advance the understanding of poorly characterized major aspects of archaeal biology.

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Rho-modifying bacterial protein toxins from Photorhabdus species

Cited by 5 publications

References 59 publications

Photorhabdus: a tale of contrasting interactions

Photorhabdus: a tale of contrasting interactions

Glycosylating Effectors of Legionella pneumophila: Finding the Sweet Spots for Host Cell Subversion

Antimicrobial Peptides, Polymorphic Toxins, and Self-Nonself Recognition Systems in Archaea: an Untapped Armory for Intermicrobial Conflicts

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