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Nature Reviews. Microbiology Sep 2014Bacterial ADP-ribosyltransferase toxins (bARTTs) transfer ADP-ribose to eukaryotic proteins to promote bacterial pathogenesis. In this Review, we use prototype bARTTs,... (Review)
Review
Bacterial ADP-ribosyltransferase toxins (bARTTs) transfer ADP-ribose to eukaryotic proteins to promote bacterial pathogenesis. In this Review, we use prototype bARTTs, such as diphtheria toxin and pertussis toxin, as references for the characterization of several new bARTTs from human, insect and plant pathogens, which were recently identified by bioinformatic analyses. Several of these toxins, including cholix toxin (ChxA) from Vibrio cholerae, SpyA from Streptococcus pyogenes, HopU1 from Pseudomonas syringae and the Tcc toxins from Photorhabdus luminescens, ADP-ribosylate novel substrates and have unique organizations, which distinguish them from the reference toxins. The characterization of these toxins increases our appreciation of the range of structural and functional properties that are possessed by bARTTs and their roles in bacterial pathogenesis.
Topics: ADP Ribose Transferases; Adenosine Diphosphate Ribose; Animals; Bacteria; Bacterial Toxins; Computational Biology; Humans; Insecta; Models, Molecular; Plants; Signal Transduction
PubMed: 25023120
DOI: 10.1038/nrmicro3310 -
Nature Microbiology Oct 2022Discovery of antibiotics acting against Gram-negative species is uniquely challenging due to their restrictive penetration barrier. BamA, which inserts proteins into the...
Discovery of antibiotics acting against Gram-negative species is uniquely challenging due to their restrictive penetration barrier. BamA, which inserts proteins into the outer membrane, is an attractive target due to its surface location. Darobactins produced by Photorhabdus, a nematode gut microbiome symbiont, target BamA. We reasoned that a computational search for genes only distantly related to the darobactin operon may lead to novel compounds. Following this clue, we identified dynobactin A, a novel peptide antibiotic from Photorhabdus australis containing two unlinked rings. Dynobactin is structurally unrelated to darobactins, but also targets BamA. Based on a BamA-dynobactin co-crystal structure and a BAM-complex-dynobactin cryo-EM structure, we show that dynobactin binds to the BamA lateral gate, uniquely protruding into its β-barrel lumen. Dynobactin showed efficacy in a mouse systemic Escherichia coli infection. This study demonstrates the utility of computational approaches to antibiotic discovery and suggests that dynobactin is a promising lead for drug development.
Topics: Animals; Anti-Bacterial Agents; Bacterial Outer Membrane Proteins; Escherichia coli; Escherichia coli Proteins; Gram-Negative Bacteria; Mice; Peptides; Phenylpropionates
PubMed: 36163500
DOI: 10.1038/s41564-022-01227-4 -
International Journal of Systematic and... Jan 2021Three Gram-stain-negative, rod-shaped, non-spore-forming bacteria, BA1, Q614 and PB68.1, isolated from the digestive system of entomopathogenic nematodes, were...
Three Gram-stain-negative, rod-shaped, non-spore-forming bacteria, BA1, Q614 and PB68.1, isolated from the digestive system of entomopathogenic nematodes, were biochemically and molecularly characterized to clarify their taxonomic affiliations. The 16S rRNA gene sequences of these strains suggest that they belong to the Gammaproteobacteria, to the family , and to the genus . Deeper analyses using whole genome-based phylogenetic reconstructions suggest that BA1 is closely related to , that Q614 is closely related to and that PB68.1 is closely related to genomic comparisons confirm these observations: BA1 and 15138 share 68.8 % digital DNA-DNA hybridization (dDDH), Q614 and SF41 share 75.4 % dDDH, and PB68.1 and DSM 17609 share 76.6 % dDDH. Physiological and biochemical characterizations reveal that these three strains also differ from all validly described species and from their more closely related taxa, contrary to what was previously suggested. We therefore propose to classify BA1 as a new species within the genus , Q614 as a new subspecies within and PB68.1 as a new subspecies within . Hence, the following names are proposed for these strains: sp. nov. with the type strain BA1(=DSM 111180=CCOS 1943=LMG 31957), subsp subsp. nov. with the type strain Q614 (=DSM 111144=CCOS 1944=LMG 31959) and subsp subsp. nov. with the type strain PB68.1 (=DSM 111145=CCOS 1942). These propositions automatically create subsp subsp. nov. with SF41 as the type strain (currently classified as ) and subsp. subsp. nov. with DSM17609 as the type strain (currently classified as ).
Topics: Animals; Australia; Bacterial Typing Techniques; Base Composition; DNA, Bacterial; Digestive System; Egypt; Nematoda; Nucleic Acid Hybridization; Photorhabdus; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Thailand
PubMed: 33464198
DOI: 10.1099/ijsem.0.004610 -
Natural Product Reports Apr 2018Covering: up to November 2017 Organismic interaction is one of the fundamental principles for survival in any ecosystem. Today, numerous examples show the interaction... (Review)
Review
Covering: up to November 2017 Organismic interaction is one of the fundamental principles for survival in any ecosystem. Today, numerous examples show the interaction between microorganisms like bacteria and higher eukaryotes that can be anything between mutualistic to parasitic/pathogenic symbioses. There is also increasing evidence that microorganisms are used by higher eukaryotes not only for the supply of essential factors like vitamins but also as biological weapons to protect themselves or to kill other organisms. Excellent examples for such systems are entomopathogenic nematodes of the genera Heterorhabditis and Steinernema that live in mutualistic symbiosis with bacteria of the genera Photorhabdus and Xenorhabdus, respectively. Although these systems have been used successfully in organic farming on an industrial scale, it was only shown during the last 15 years that several different natural products (NPs) produced by the bacteria play key roles in the complex life cycle of the bacterial symbionts, the nematode host and the insect prey that is killed by and provides nutrients for the nematode-bacteria pair. Since the bacteria can switch from mutualistic to pathogenic lifestyle, interacting with two different types of higher eukaryotes, and since the full system with all players can be established in the lab, they are promising model systems to elucidate the natural function of microbial NPs. This review summarizes the current knowledge as well as open questions for NPs from Photorhabdus and Xenorhabdus and tries to assign their roles in the tritrophic relationship.
Topics: Animals; Bacteria; Bacterial Physiological Phenomena; Biological Products; Host-Pathogen Interactions; Insecta; Life Cycle Stages; Nematoda; Organic Agriculture; Photorhabdus; Symbiosis; Xenorhabdus
PubMed: 29359226
DOI: 10.1039/c7np00054e -
Frontiers in Insect Science 2023The term "microbial control" has been used to describe the use of microbial pathogens (bacteria, viruses, or fungi) or entomopathogenic nematodes (EPNs) to control... (Review)
Review
The term "microbial control" has been used to describe the use of microbial pathogens (bacteria, viruses, or fungi) or entomopathogenic nematodes (EPNs) to control various insect pest populations. EPNs are among the best biocontrol agents, and major developments in their use have occurred in recent decades, with many surveys having been conducted all over the world to identify EPNs that may have potential in the management of insect pests. For nematodes, the term "entomopathogenic" means "causing disease to insects" and is mainly used in reference to the bacterial symbionts of and ( and , respectively), which cause EPN infectivity. A compendium of our multiannual experiences on EPN surveys and on their collection, identification, characterization, and use in agro-forestry ecosystems is presented here to testify and demonstrate once again that biological control with EPNs is possible and offers many advantages over chemicals, such as end-user safety, minimal damage to natural enemies, and lack of environmental pollution, which are essential conditions for an advanced IPM strategy.
PubMed: 38469514
DOI: 10.3389/finsc.2023.1195254 -
Current Topics in Microbiology and... 2015The ADP-ribosyltransferases TccC3 and TccC5 are the biologically active TcC components of the tripartite Photorhabdus luminescens Tc toxin, which consist of TcA, TcB,... (Review)
Review
The ADP-ribosyltransferases TccC3 and TccC5 are the biologically active TcC components of the tripartite Photorhabdus luminescens Tc toxin, which consist of TcA, TcB, and TcC components. TcA is the binding and membrane translocation component. TcB is a functional linker between TcC and TcA and also involved in the translocation of the toxin. While TccC3 ADP-ribosylates actin at threonine 148, TccC5 modifies Rho proteins at glutamine 61/63. Both modifications result in major alteration of the actin cytoskeleton. Here we discuss structure and function of the Tc toxin and compare its ADP-ribosyltransferase activities with other types of actin and Rho modifying toxins.
Topics: ADP Ribose Transferases; Bacterial Proteins; Bacterial Toxins; Glutamine; Insecticides; Photorhabdus; Threonine
PubMed: 24908144
DOI: 10.1007/82_2014_382 -
Parasites & Vectors Jul 2020The control of insects of medical importance, such as Aedes aegypti and Aedes albopictus are still the only effective way to prevent the transmission of diseases, such... (Review)
Review
The control of insects of medical importance, such as Aedes aegypti and Aedes albopictus are still the only effective way to prevent the transmission of diseases, such as dengue, chikungunya and Zika. Their control is performed mainly using chemical products; however, they often have low specificity to non-target organisms, including humans. Also, studies have reported resistance to the most commonly used insecticides, such as the organophosphate and pyrethroids. Biological control is an ecological and sustainable method since it has a slow rate of insect resistance development. Bacterial species of the genera Xenorhabdus and Photorhabdus have been the target of several research groups worldwide, aiming at their use in agricultural, pharmaceutical and industrial products. This review highlights articles referring to the use of Xenorhabdus and Photorhabdus for insects and especially for mosquito control proposing future ways for their biotechnological applicability. Approximately 24 species of Xenorhabdus and five species of Photorhabdus have been described to have insecticidal properties. These studies have shown genes that are capable of encoding low molecular weight proteins, secondary toxin complexes and metabolites with insecticide activities, as well as antibiotic, fungicidal and antiparasitic molecules. In addition, several species of Xenorhabdus and Photorhabdus showed insecticidal properties against mosquitoes. Therefore, these biological agents can be used in new control methods, and must be, urgently considered in short term, in studies and applications, especially in mosquito control.
Topics: Aedes; Animals; Bacterial Toxins; Chikungunya Fever; Dengue; Genes, Bacterial; Insecta; Insecticides; Larva; Mosquito Control; Mosquito Vectors; Pest Control, Biological; Photorhabdus; Vector Borne Diseases; Xenorhabdus; Zika Virus Infection
PubMed: 32727530
DOI: 10.1186/s13071-020-04236-6 -
Frontiers in Microbiology 2020Temperature plays an important role in bacteria-host interactions and can be a determining factor for host switching. In this study we sought to investigate the reasons...
Temperature plays an important role in bacteria-host interactions and can be a determining factor for host switching. In this study we sought to investigate the reasons behind growth temperature restriction in the entomopathogenic enterobacterium . has a complex dual symbiotic and pathogenic life cycle. The genus consists of 19 species but only one subgroup, previously all classed together as , have been shown to cause human disease. These clinical isolates necessarily need to be able to grow at 37°C, whilst the remaining species are largely restricted to growth temperatures below 34°C and are therefore unable to infect mammalian hosts. Here, we have isolated spontaneous mutant lines of DJC that were able to grow up to 36-37°C. Following whole genome sequencing of 29 of these mutants we identified a single gene, encoding a protein with a RecG-like helicase domain that for the majority of isolates contained single nucleotide polymorphisms. Importantly, provision of the wild-type allele of this gene in restored the temperature restriction, confirming the mutations are recessive, and the dominant effect of the protein product of this gene. The gene appears to be part of a short three cistron operon, which we have termed the Temperature Restricting Locus (TRL). Transcription reporter strains revealed that this operon is induced upon the switch from 30 to 36°C, leading to replication arrest of the bacteria. TRL is absent from all of the human pathogenic species so far examined, although its presence is not uniform in different strains of the subgroup. In a wider context, the presence of this gene is not limited to , being found in phylogenetically diverse proteobacteria. We therefore suggest that this system may play a more fundamental role in temperature restriction in diverse species, relating to as yet cryptic aspects of their ecological niches and life cycle requirements.
PubMed: 33101227
DOI: 10.3389/fmicb.2020.548800 -
Journal of Molecular Biology Nov 2019Phenotypic heterogeneity in bacterial cell populations allows genetically identical organisms to different behavior under similar environmental conditions. The... (Review)
Review
Phenotypic heterogeneity in bacterial cell populations allows genetically identical organisms to different behavior under similar environmental conditions. The Gram-negative bacterium Photorhabdus luminescens is an excellent organism to study phenotypic heterogeneity since their life cycle involves a symbiotic interaction with soil nematodes as well as a pathogenic association with insect larvae. Phenotypic heterogeneity is highly distinct in P. luminescens. The bacteria exist in two phenotypic forms that differ in various morphologic and phenotypic traits and are therefore distinguished as primary (1°) and secondary (2°) cells. The 1 cells are bioluminescent, pigmented, produce several secondary metabolites and exo-enzymes, and support nematode growth and development. The 2° cells lack all these 1°-specific phenotypes. The entomopathogenic nematodes carry 1° cells in their upper gut and release them into an insect's body after slipping inside. During insect infection, up to the half number of 1° cells undergo phenotypic switching and convert to 2° cells. Since the 2° cells are not able to live in nematode symbiosis any more, they cannot re-associate with their symbiosis partners after the infection and remain in the soil. Phenotypic switching in P. luminescens has to be tightly regulated since a high switching frequency would lead to a complete break-down of the nematode-bacteria life cycle. Here, we present the main regulatory mechanisms known to-date that are important for phenotypic switching in P. luminescens cell populations and discuss the biological reason as well as the fate of the 2° cells in the soil.
Topics: Bacterial Physiological Phenomena; Bacterial Proteins; Biological Variation, Population; Gene Expression Regulation, Bacterial; Life Cycle Stages; Phenotype; Photorhabdus; Pigmentation; Quorum Sensing; Symbiosis
PubMed: 31022406
DOI: 10.1016/j.jmb.2019.04.015 -
Plants (Basel, Switzerland) Aug 2021The current approaches to sustainable agricultural development aspire to use safer means to control pests and pathogens. bacteria that are insecticidal symbionts of... (Review)
Review
The current approaches to sustainable agricultural development aspire to use safer means to control pests and pathogens. bacteria that are insecticidal symbionts of entomopathogenic nematodes in the genus can provide such a service with a treasure trove of insecticidal compounds and an ability to cope with the insect immune system. This review highlights the need of -derived insecticidal, fungicidal, pharmaceutical, parasiticidal, antimicrobial, and toxic materials to fit into current, or emerging, holistic strategies, mainly for managing plant pests and pathogens. The widespread use of these bacteria, however, has been slow, due to cost, natural presence within the uneven distribution of their nematode partners, and problems with trait stability during in vitro culture. Yet, progress has been made, showing an ability to overcome these obstacles via offering affordable mass production and mastered genome sequencing, while detecting more of their beneficial bacterial species/strains. Their high pathogenicity to a wide range of arthropods, efficiency against diseases, and versatility, suggest future promising industrial products. The many useful properties of these bacteria can facilitate their integration with other pest/disease management tactics for crop protection.
PubMed: 34451705
DOI: 10.3390/plants10081660