-
Microbiology (Reading, England) Apr 2020Different model systems have, over the years, contributed to our current understanding of the molecular mechanisms underpinning the various types of interaction between... (Review)
Review
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 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 . 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 has three distinct and obligate roles to play during this life-cycle: (1) must kill the insect host; (2) must be capable of supporting nematode growth and development; and (3) 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 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.
Topics: Animals; Bacterial Toxins; Gastrointestinal Tract; Host Microbial Interactions; Insecta; Life Cycle Stages; Photorhabdus; Rhabditoidea; Signal Transduction; Symbiosis
PubMed: 32209172
DOI: 10.1099/mic.0.000907 -
Applied Microbiology and Biotechnology Jun 2022Insects and fungal pathogens pose constant problems to public health and agriculture, especially in resource-limited parts of the world; and the use of chemical... (Review)
Review
Insects and fungal pathogens pose constant problems to public health and agriculture, especially in resource-limited parts of the world; and the use of chemical pesticides continues to be the main methods for the control of these organisms. Photorhabdus spp. and Xenorhabdus spp., (Fam; Morganellaceae), enteric symbionts of Steinernema, and Heterorhabditis nematodes are naturally found in soil on all continents, except Antarctic, and on many islands throughout the world. These bacteria produce diverse secondary metabolites that have important biological and ecological functions. Secondary metabolites include non-ribosomal peptides, polyketides, and/or hybrid natural products that are synthesized using polyketide synthetase (PRS), non-ribosomal peptide synthetase (NRPS), or similar enzymes and are sources of new pesticide/drug compounds and/or can serve as lead molecules for the design and synthesize of new alternatives that could replace current ones. This review addresses the effects of these bacterial symbionts on insect pests, fungal phytopathogens, and animal pathogens and discusses the substances, mechanisms, and impacts on agriculture and public health. KEY POINTS: • Insects and fungi are a constant menace to agricultural and public health. • Chemical-based control results in resistance development. • Photorhabdus and Xenorhabdus are compelling sources of biopesticides.
Topics: Animals; Biological Products; Insecta; Nematoda; Photorhabdus; Rhabditida; Symbiosis; Xenorhabdus
PubMed: 35723692
DOI: 10.1007/s00253-022-12023-9 -
Nature Apr 2023Endosymbiotic bacteria have evolved intricate delivery systems that enable these organisms to interface with host biology. One example, the extracellular contractile...
Endosymbiotic bacteria have evolved intricate delivery systems that enable these organisms to interface with host biology. One example, the extracellular contractile injection systems (eCISs), are syringe-like macromolecular complexes that inject protein payloads into eukaryotic cells by driving a spike through the cellular membrane. Recently, eCISs have been found to target mouse cells, raising the possibility that these systems could be harnessed for therapeutic protein delivery. However, whether eCISs can function in human cells remains unknown, and the mechanism by which these systems recognize target cells is poorly understood. Here we show that target selection by the Photorhabdus virulence cassette (PVC)-an eCIS from the entomopathogenic bacterium Photorhabdus asymbiotica-is mediated by specific recognition of a target receptor by a distal binding element of the PVC tail fibre. Furthermore, using in silico structure-guided engineering of the tail fibre, we show that PVCs can be reprogrammed to target organisms not natively targeted by these systems-including human cells and mice-with efficiencies approaching 100%. Finally, we show that PVCs can load diverse protein payloads, including Cas9, base editors and toxins, and can functionally deliver them into human cells. Our results demonstrate that PVCs are programmable protein delivery devices with possible applications in gene therapy, cancer therapy and biocontrol.
Topics: Animals; Humans; Mice; Cell Membrane; Eukaryotic Cells; Photorhabdus; CRISPR-Associated Protein 9; Toxins, Biological; Proteins; Drug Delivery Systems; Protein Transport
PubMed: 36991127
DOI: 10.1038/s41586-023-05870-7 -
Annual Review of Microbiology 2009Photorhabdus is a member of the family Enterobacteriaceae that lives in a mutualistic association with a Heterorhabditis nematode worm. The nematode worm burrows into... (Review)
Review
Photorhabdus is a member of the family Enterobacteriaceae that lives in a mutualistic association with a Heterorhabditis nematode worm. The nematode worm burrows into insect prey and regurgitates Photorhabdus, which goes on to kill the insect. The nematode feeds off the growing bacteria until the insect tissues are exhausted, whereupon they reassociate and leave the cadaver in search of new prey. This highly efficient partnership has been used for many years as a biological crop protection agent. The dual nature of Photorhabdus as a pathogen and mutualist makes it a superb model for understanding these apparently exclusive activities. Furthermore, recently identified clinical isolates of Photorhabdus are helping us to understand how human pathogens can emerge from the enormous reservoir of invertebrate pathogens in the environment. As Photorhabdus has never been found outside a host animal, its niche represents an entirely biotic landscape. In this review we discuss what molecular adaptations allow this bacterium to complete this fascinating and complex life cycle.
Topics: Animals; Host-Parasite Interactions; Host-Pathogen Interactions; Insecta; Photorhabdus; Rhabditoidea; Symbiosis
PubMed: 19575559
DOI: 10.1146/annurev.micro.091208.073507 -
Current Topics in Microbiology and... 2017Actin is one of the most abundant cellular proteins and an essential constituent of the actin cytoskeleton, which by its dynamic behavior participates in many cellular... (Review)
Review
Actin is one of the most abundant cellular proteins and an essential constituent of the actin cytoskeleton, which by its dynamic behavior participates in many cellular activities. The organization of the actin cytoskeleton is regulated by a large number of proteins and represents one of the major targets of bacterial toxins. A number of bacterial effector proteins directly modify actin: Clostridial bacteria produce toxins, which ADP-ribosylate actin at Arg177 leading to inhibition of actin polymerization. The bacterium Photorhabdus luminescens produces several types of protein toxins, including the high molecular weight Tc toxin complex, whose component TccC3 ADP-ribosylates actin at Thr148 promoting polymerization and aggregation of intracellular F-actin leading to inhibition of several cellular functions, such as phagocytosis. Here, we review recent findings about the functional consequences of these actin modifications and for the Thr148-ADP-ribosylated actin the subsequent alterations in the interaction with actin-binding proteins . In addition, we describe the effects of ADP-ribosylation of Rho GTPases by the TccC5 component.
Topics: Actins; Animals; Bacterial Toxins; Cell Movement; Enterobacteriaceae Infections; Humans; Microfilament Proteins; Photorhabdus; Protein Binding
PubMed: 27757548
DOI: 10.1007/82_2016_43 -
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 -
FEMS Microbiology Reviews Jan 2003Pathogenicity and symbiosis are central to bacteria-host interactions. Although several human pathogens have been subjected to functional genomic analysis, we still... (Review)
Review
Pathogenicity and symbiosis are central to bacteria-host interactions. Although several human pathogens have been subjected to functional genomic analysis, we still understand little about bacteria-invertebrate interactions despite their ecological prevalence. Advances in our knowledge of this area are often hindered by the difficulty of isolating and working with invertebrate pathogenic bacteria and their hosts. Here we review studies on pathogenicity and symbiosis in an insect pathogenic bacterium Photorhabdus and its entomopathogenic nematode vector and model insect hosts. Whilst switching between these hosts, Photorhabdus changes from a state of symbiosis with its nematode vector to one of pathogenicity towards its new insect host and both the bacteria and the nematode then cooperatively exploit the dying insect. We examine candidate genes involved in symbiosis and pathogenicity, their secretion and expression patterns in culture and in the host, and begin to dissect the extent of their genetic coregulation. We describe the presence of several large genomic islands, putatively involved in pathogenicity or symbiosis, within the otherwise Yersinia-like backbone of the Photorhabdus genome. Finally, we examine the emerging comparative genomics of the Photorhabdus group and begin to describe the interrelationship between anti-invertebrate virulence factors and those used against vertebrates.
Topics: Animals; Bacteriocins; Bacteriophages; Genome, Bacterial; Insecta; Life Cycle Stages; Models, Genetic; Nematoda; Photorhabdus; Symbiosis; Virulence Factors
PubMed: 12586390
DOI: 10.1111/j.1574-6976.2003.tb00625.x -
Cellular Microbiology Nov 2008Photorhabdus are entomopathogenic members of the family Enterobacteriaceae. In addition to killing insects Photorhabdus also have a mutualistic association with... (Review)
Review
Photorhabdus are entomopathogenic members of the family Enterobacteriaceae. In addition to killing insects Photorhabdus also have a mutualistic association with nematodes from the family Heterorhabditidiae. Therefore, the bacteria have a complex life cycle that involves temporally separated pathogenic and mutualistic associations with two different invertebrate hosts. This tripartite Photorhabdus-insect-nematode association provides researchers with a unique opportunity to characterize the prokaryotic contribution to two different symbioses, i.e. pathogenicity and mutualism while also studying the role of the host in determining the outcome of association with the bacteria. In this review I will outline the life cycle of Photorhabdus and describe recent important advances in our understanding of the symbiology of Photorhabdus. Finally, the contribution made by this model to our understanding of the nature of symbiotic associations will be discussed.
Topics: Animals; Host-Parasite Interactions; Immunity, Innate; Insecta; Models, Biological; Nematoda; Photorhabdus; Signal Transduction; Symbiosis
PubMed: 18647173
DOI: 10.1111/j.1462-5822.2008.01209.x -
Toxins Jun 2010Photorhabdus luminescens is a nematode-symbiotic, gram negative, bioluminescent bacterium, belonging to the family of Enterobacteriaceae. Recent studies show the... (Review)
Review
Photorhabdus luminescens is a nematode-symbiotic, gram negative, bioluminescent bacterium, belonging to the family of Enterobacteriaceae. Recent studies show the importance of this bacterium as an alternative source of insecticides, as well as an emerging human pathogen. Various toxins have been identified and characterized in this bacterium. These toxins are classified into four major groups: the toxin complexes (Tcs), the Photorhabdus insect related (Pir) proteins, the "makes caterpillars floppy" (Mcf) toxins and the Photorhabdus virulence cassettes (PVC); the mechanisms however of toxin secretion are not fully elucidated. Using bioinformatics analysis and comparison against the components of known secretion systems, multiple copies of components of all known secretion systems, except the ones composing a type IV secretion system, were identified throughout the entire genome of the bacterium. This indicates that Photorhabdus luminescens has all the necessary means for the secretion of virulence factors, thus it is capable of establishing a microbial infection.
Topics: Bacterial Proteins; Bacterial Toxins; Humans; Photorhabdus
PubMed: 22069636
DOI: 10.3390/toxins2061250 -
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