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The Journal of Biological Chemistry Dec 2017Lectins play important roles in infections by pathogenic bacteria, for example, in host colonization, persistence, and biofilm formation. The Gram-negative...
Lectins play important roles in infections by pathogenic bacteria, for example, in host colonization, persistence, and biofilm formation. The Gram-negative entomopathogenic bacterium symbiotically lives in insect-infecting nematodes and kills the insect host upon invasion by the nematode. The genome harbors the gene , coding for a novel lectin that we named PllA. We analyzed the binding properties of purified PllA with a glycan array and a binding assay in solution. Both assays revealed a strict specificity of PllA for α-galactoside-terminating glycoconjugates. The crystal structures of apo PllA and complexes with three different ligands revealed the molecular basis for the strict specificity of this lectin. Furthermore, we found that a 90° twist in subunit orientation leads to a peculiar quaternary structure compared with that of its ortholog LecA from We also investigated the utility of PllA as a probe for detecting α-galactosides. The α-Gal epitope is present on wild-type pig cells and is the main reason for hyperacute organ rejection in pig to primate xenotransplantation. We noted that PllA specifically recognizes this epitope on the glycan array and demonstrated that PllA can be used as a fluorescent probe to detect this epitope on primary porcine cells In summary, our biochemical and structural analyses of the lectin PllA have disclosed the structural basis for PllA's high specificity for α-galactoside-containing ligands, and we show that PllA can be used to visualize the α-Gal epitope on porcine tissues.
Topics: Amino Acid Sequence; Animals; Galactosides; Glycoconjugates; Hemagglutination Tests; Lectins; Molecular Probes; Photorhabdus; Protein Binding; Protein Conformation; Sequence Homology, Amino Acid; Swine
PubMed: 28972138
DOI: 10.1074/jbc.M117.812792 -
Biology Oct 2021and are considered a global threat to agricultural crops and food security; hence, their control is a critical issue. and nematodes, along with their symbiotic...
and are considered a global threat to agricultural crops and food security; hence, their control is a critical issue. and nematodes, along with their symbiotic bacteria, can achieve the optimal biocontrol agent criterion. Therefore, this study aimed to evaluate the efficacy of , and their symbiotic bacteria ( and ) against and larvae. The virulence of entomopathogenic nematodes (EPNs) was determined at different infective juvenile concentrations and exposure times, while the symbiotic bacteria were applied at the concentration of 3 × 10 colony-forming units (CFU)/mL at different exposure times. Gas chromatography-mass spectrophotometry (GC-MS) analysis and the cytotoxic effect of sp. and sp. were determined. The results indicated that . , . , and their symbiotic bacteria significantly ( ≤ 0.001) induced mortality in both insect species. However, . and its symbiont, sp., were more virulent. Moreover, the data clarified that both symbiotic bacteria outperformed EPNs against but the opposite was true for GC-MS analysis revealed the main active compounds that have insecticidal activity. However, the results revealed that there was no significant cytotoxic effect. In conclusion, . , . , and their symbiotic bacteria can be an optimal option for bio-controlling both insect species. Furthermore, both symbiotic bacteria can be utilized independently on EPNs for the management of both pests, and, hence, they can be safely incorporated into biocontrol programs and tested against other insect pests.
PubMed: 34681098
DOI: 10.3390/biology10100999 -
Current Topics in Microbiology and... 2017A general definition of secondary metabolism is that it consists of the metabolic pathways and the products of metabolism that are not absolutely required for the...
A general definition of secondary metabolism is that it consists of the metabolic pathways and the products of metabolism that are not absolutely required for the survival of the organism. Using this definition, it is now well established that Photorhabdus elaborate an extensive secondary metabolism during the post-exponential phase of bacterial growth. This secondary metabolism includes, but is not limited to, the production of light, a stilbene antibiotic and an anthraquinone pigment. In this chapter, the role of secondary metabolism during the life cycle of Photorhabdus will be discussed. Recent work has shown that secondary metabolism in Photorhabdus is required for the mutualistic association between the bacteria and its nematode partner, in particular bacterial secondary metabolism is required to support normal nematode growth and development. An isogenic population of Photorhabdus is phenotypically heterogenous and this facilitates functional partitioning within the population. The relationship between secondary metabolism and the various phenotypic and phase variants that exist in populations of Photorhabdus will also be discussed. Finally, this chapter will also describe the various regulatory nodes that have been identified as being part of the complex regulatory network that is used to control the temporal expression of secondary metabolism in Photorhabdus.
Topics: Anthraquinones; Photorhabdus; Secondary Metabolism; Symbiosis
PubMed: 27469305
DOI: 10.1007/82_2016_21 -
Frontiers in Microbiology 2019A major issue currently facing medicine is antibiotic resistance. No new class of antibiotics for the treatment of Gram-negative infections has been introduced in more... (Review)
Review
A major issue currently facing medicine is antibiotic resistance. No new class of antibiotics for the treatment of Gram-negative infections has been introduced in more than 40 years. We screened a collection of and strains in the quest to discover new structures that are active against the most problematic multidrug-resistant bacteria. These species are symbiotic bacteria of entomopathogenic nematodes and their life cycle, the richness of the bacteria's genome in non-ribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) genes, and their propensity to produce secondary metabolites with a large diversity of chemical structures make them a good starting point to begin an ambitious drug discovery program. Odilorhabdins (ODLs), a novel antibacterial class, were identified from this campaign. These compounds inhibit bacterial translation by binding to the small ribosomal subunit at a site not exploited by current antibiotics. Following the development of the total synthesis of this family of peptides, a medicinal chemistry program was started to optimize their pharmacological properties. NOSO-502, the first ODL preclinical candidate was selected. This compound is currently under preclinical development for the treatment of multidrug-resistant Gram-negative infections in hospitalized patients.
PubMed: 31921069
DOI: 10.3389/fmicb.2019.02893 -
Environmental Microbiology Reports Dec 2022Photorhabdus, the symbiotic bacteria of Heterorhabditis nematodes, has been reported to possess many non-ribosomal peptide synthetase (NRPS) biosynthesis gene clusters...
Photorhabdus, the symbiotic bacteria of Heterorhabditis nematodes, has been reported to possess many non-ribosomal peptide synthetase (NRPS) biosynthesis gene clusters (BGCs). To provide an in-depth assessment of the non-ribosomal peptide biosynthetic potential of Photorhabdus, we compared the distribution of BGCs in 81 Photorhabdus strains, confirming the predominant presence (44.80%) of NRPS BGCs in Photorhabdus. All 990 NRPS BGCs were clustered into 275 gene cluster families (GCFs) and only 13 GCFs could be annotated with known BGCs, suggesting their great diversity and novelty. These NRPS BGCs encoded 351 novel peptides containing more than four amino acids, and 173 of them showed high sequence similarity to known BGCs encoding bioactive peptides, implying the promising potential of Photorhabdus to produce valuable peptides. Sequence similarity networking of adenylation (A-) domains suggested that the substrate specificity of A-domains was not directly correlated with the sequence similarity. The molecular similarity network of predicted metabolite scaffolds of NRPS BGCs and reported peptides from Photorhabdus and a relevant database demonstrated that the non-ribosomal peptide biosynthetic potential of Photorhabdus was largely untapped and revealed the core peptides deserving intensive studies. Our present study provides valuable information for the targeted discovery of novel non-ribosomal peptides from Photorhabdus.
Topics: Animals; Photorhabdus; Nematoda; Multigene Family; Symbiosis; Peptides
PubMed: 35998886
DOI: 10.1111/1758-2229.13118 -
Genetically modified entomopathogenic bacteria, recent developments, benefits and impacts: A review.The Science of the Total Environment Sep 2020Entomopathogenic bacteria (EPBs), insect pathogens that produce pest-specific toxins, are environmentally-friendly alternatives to chemical insecticides. However, the... (Review)
Review
Entomopathogenic bacteria (EPBs), insect pathogens that produce pest-specific toxins, are environmentally-friendly alternatives to chemical insecticides. However, the most important problem with EPBs application is their limited field stability. Moreover, environmental factors such as solar radiation, leaf temperature, and vapor pressure can affect the pathogenicity of these pathogens and their toxins. Scientists have conducted intensive research to overcome such problems. Genetic engineering has great potential for the development of new engineered entomopathogens with more resistance to adverse environmental factors. Genetically modified entomopathogenic bacteria (GM-EPBs) have many advantages over wild EPBs, such as higher pathogenicity, lower spraying requirements and longer-term persistence. Genetic manipulations have been mostly applied to members of the bacterial genera Bacillus, Lysinibacillus, Pseudomonas, Serratia, Photorhabdus and Xenorhabdus. Although many researchers have found that GM-EPBs can be used safely as plant protection bioproducts, limited attention has been paid to their potential ecological impacts. The main concerns about GM-EPBs and their products are their potential unintended effects on beneficial insects (predators, parasitoids, pollinators, etc.) and rhizospheric bacteria. This review address recent update on the significant role of GM-EPBs in biological control, examining them through different perspectives in an attempt to generate critical discussion and aid in the understanding of their potential ecological impacts.
Topics: Animals; Genetic Engineering; Insecta; Insecticides; Pest Control, Biological; Photorhabdus; Xenorhabdus
PubMed: 32460068
DOI: 10.1016/j.scitotenv.2020.139169 -
Proceedings of the National Academy of... Jan 2015It is well recognized that bacteria communicate via small diffusible molecules, a process termed quorum sensing. The best understood quorum sensing systems are those...
It is well recognized that bacteria communicate via small diffusible molecules, a process termed quorum sensing. The best understood quorum sensing systems are those that use acylated homoserine lactones (AHLs) for communication. The prototype of those systems consists of a LuxI-like AHL synthase and a cognate LuxR receptor that detects the signal. However, many proteobacteria possess LuxR receptors, yet lack any LuxI-type synthase, and thus these receptors are referred to as LuxR orphans or solos. In addition to the well-known AHLs, little is known about the signaling molecules that are sensed by LuxR solos. Here, we describe a novel cell-cell communication system in the insect and human pathogen Photorhabdus asymbiotica. We identified the LuxR homolog PauR to sense dialkylresorcinols (DARs) and cyclohexanediones (CHDs) instead of AHLs as signals. The DarABC synthesis pathway produces the molecules, and the entire system emerged as important for virulence. Moreover, we have analyzed more than 90 different Photorhabdus strains by HPLC/MS and showed that these DARs and CHDs are specific to the human pathogen P. asymbiotica. On the basis of genomic evidence, 116 other bacterial species are putative DAR producers, among them many human pathogens. Therefore, we discuss the possibility of DARs as novel and widespread bacterial signaling molecules and show that bacterial cell-cell communication goes far beyond AHL signaling in nature.
Topics: Acyl-Butyrolactones; Amino Acid Sequence; Animals; Bacterial Proteins; Base Sequence; Conserved Sequence; Cyclohexanones; DNA, Bacterial; Genes, Bacterial; Humans; Models, Biological; Models, Molecular; Molecular Sequence Data; Operon; Photorhabdus; Phylogeny; Protein Conformation; Quorum Sensing; Repressor Proteins; Resorcinols; Sequence Homology, Amino Acid; Signal Transduction; Trans-Activators
PubMed: 25550519
DOI: 10.1073/pnas.1417685112 -
Frontiers in Microbiology 2023Contractile injection systems (CISs) are phage tail-related structures that are encoded in many bacterial genomes. These devices encompass the cell-based type VI... (Review)
Review
Contractile injection systems (CISs) are phage tail-related structures that are encoded in many bacterial genomes. These devices encompass the cell-based type VI secretion systems (T6SSs) as well as extracellular CISs (eCISs). The eCISs comprise the R-tailocins produced by various bacterial species as well as related phage tail-like structures such as the antifeeding prophages (Afps) of , the virulence cassettes (PVCs), and the metamorphosis-associated contractile structures (MACs) of . These contractile structures are released into the extracellular environment upon suicidal lysis of the producer cell and play important roles in bacterial ecology and evolution. In this review, we specifically portray the eCISs with a focus on the R-tailocins, sketch the history of their discovery and provide insights into their evolution within the bacterial host, their structures and how they are assembled and released. We then highlight ecological and evolutionary roles of eCISs and conceptualize how they can influence and shape bacterial communities. Finally, we point to their potential for biotechnological applications in medicine and agriculture.
PubMed: 37886057
DOI: 10.3389/fmicb.2023.1264877 -
The Journal of Parasitology Jan 2023The entomopathogenic nematode (EPN) Heterorhabditis bacteriophora infects a wide range of insect hosts with the aid of its mutualistic bacteria Photorhabdus luminescens....
The entomopathogenic nematode (EPN) Heterorhabditis bacteriophora infects a wide range of insect hosts with the aid of its mutualistic bacteria Photorhabdus luminescens. While the mutualistic relationship between H. bacteriophora and P. luminescens and the infectivity of the nematode-bacteria complex have been characterized, how nematode fitness is affected by entomopathogenic bacteria existing in association with other EPN species remains poorly understood. In this study, the survival of H. bacteriophora infective juveniles containing or lacking P. luminescens was tested against the entomopathogenic bacteria Xenorhabdus nematophila and Photorhabdus asymbiotica as well as the non-pathogenic Escherichia coli. While X. nematophila and E. coli did not significantly affect the survival of H. bacteriophora, P. asymbiotica exerted a significant effect on nematode survival, particularly on those lacking P. luminescens. These results imply that P. asymbiotica encodes factors that are pathogenic to EPNs. Future efforts will focus on the identification of the bacterial molecular components that induce these effects. This study makes an important contribution to a growing body of research aimed at exploiting the full potential of nematode-bacterial complexes for eliminating noxious insect pests and treating infectious diseases caused by parasitic nematodes.
Topics: Animals; Photorhabdus; Escherichia coli; Nematoda; Symbiosis
PubMed: 36805240
DOI: 10.1645/22-55 -
Journal of Invertebrate Pathology Feb 2022Recovery, yield, and dispersal are crucial developmental and behavioral indices for the infective juveniles of entomopathogenic nematodes, which are used as biocontrol...
Recovery, yield, and dispersal are crucial developmental and behavioral indices for the infective juveniles of entomopathogenic nematodes, which are used as biocontrol agents against a variety of agricultural pests. Ascarosides and isopropylstilbene (ISO) function as nematode pheromones with developmental and behavioral effects. In this study, 11 synthesized ascarosides identified from Caenorhabditis elegans, together with ISO identified from Photorhabdus luminescens, were used to determine their influence on the IJ recovery, growth on agar plates, and dispersal of S. carpocapsae All, H. bacteriophora H06 and H. indica LN2 nematodes. Compared with the controls, significant differences in IJ recovery of three nematode species were detected from the supernatants of their corresponding bacterial cultures with almost all ascarosides or isopropylstilbene (ISO) at 0.04 nM in 6 days. The highest IJ recovery percentages was obtained from ISO and ascr#3 for All strain, ascr#5 and ascr#6 for LN2 strain, and ISO and ascr#12 for H06 strain. The ISO detected from Photorhabdus bacteria also induced IJ recovery of S. carpocapsae All. IJ yields was significantly stimulated by all synthesized compounds for S. carpocapsae All, and by most compounds for H. bacteriophora H06. The higher IJ yields varied with ascarosides. Ascr#7 and DMSO was common for the improved IJ yields of both nematode species. The three nematode species showed marked differences in dispersal behavior. In response to the ascarosides or ISO, S. carpocapsae All IJs actively moved with different dispersal rates, H. indica LN2 IJs in very low dispersal rates, and H. bacteriophora H06 IJs in variable and even suppressed rates on the agar plates at least during the assay period. Based on the synthesized standards, ascr#1, ascr#9 and ascr#10 were detected from three nematode species, ascr#5 and ascr#11 also from S. carpocapsae All and H. bacteriophora H06, and ascr#12 also from H. bacteriophora H06 and H. indica LN2. Ascr#9 was most abundant in three nematode species. Compared with the sterile PBS, significantly more ascr#1, ascr#9 and ascr#10 were detected from S. carpocapsae All and H. indica LN2, but less ascr#5 and ascr#11 from S. carpocapsae All, ascr#1, ascr#5, ascr#11 and ascr#12 from H. bacteriophora H06, in the corresponding bacterial supernatant. It seems that the bacterial supernatants could regulate the ascaroside secretion by the three nematode species. These results will provide useful clues for selecting suitable ascarosides to induce the recovery, improve the yield, and enhance the dispersal of the IJs of these nematodes.
Topics: Agar; Animals; Nematoda; Pheromones; Photorhabdus
PubMed: 35031295
DOI: 10.1016/j.jip.2022.107717