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Journal of Natural Products Dec 2019A new cyclic peptide photoditritide (), containing two rare amino acid d-homoarginine residues, was isolated from Meg1 after the nonribosomal peptide synthetase...
A new cyclic peptide photoditritide (), containing two rare amino acid d-homoarginine residues, was isolated from Meg1 after the nonribosomal peptide synthetase encoding gene was activated via promoter exchange. The structure of was elucidated by HR-MS and NMR experiments. The absolute configurations of amino acids were determined according to the advanced Marfey's method after hydrolysis of . Bioactivity testing of revealed potent antimicrobial activity against with an MIC value of 3.0 μM and weak antiprotozoal activity against with an IC value of 13 μM. Additionally, the biosynthetic pathway of was also proposed.
Topics: Anti-Bacterial Agents; Antiprotozoal Agents; Microbial Sensitivity Tests; Micrococcus luteus; Molecular Structure; Photorhabdus; Spectrum Analysis; Trypanosoma brucei rhodesiense
PubMed: 31799840
DOI: 10.1021/acs.jnatprod.9b00932 -
Organic & Biomolecular Chemistry Aug 2019A new natural product compound library, photohexapeptide library, was identified from entomopathogenic Photorhabdus asymbiotica PB68.1 after the NRPS-encoding gene phpS...
A new natural product compound library, photohexapeptide library, was identified from entomopathogenic Photorhabdus asymbiotica PB68.1 after the NRPS-encoding gene phpS was activated via promoter exchange. Peptide structures, including the absolute configurations of amino acids, were determined by using a combination of bioinformatics analysis and isotopic labelling experiments followed by detailed HPLC-MS analysis. Additionally, their structures were confirmed by chemical synthesis and NMR after preparative isolation. The chemical diversity of the photohexapeptides results from promiscuous adenylation domain specificity being an excellent example of how to create libraries in nature.
Topics: Bacterial Proteins; Computational Biology; Genes, Bacterial; Isotope Labeling; Molecular Structure; Oligopeptides; Peptide Library; Peptide Synthases; Photorhabdus; Transcriptional Activation
PubMed: 31403156
DOI: 10.1039/c9ob01489f -
Parasitology Jul 2018Leishmaniasis is a widely spread and zoonotic disease with serious problems as low effectiveness of drugs, emergence of parasite resistance and severe adverse reactions....
Leishmaniasis is a widely spread and zoonotic disease with serious problems as low effectiveness of drugs, emergence of parasite resistance and severe adverse reactions. In recent years, considerable attention has been given to secondary metabolites produced by Photorhabdus luminescens, an entomopathogenic bacterium. Here, we assessed the leishmanicidal activity of P. luminescens culture fluids. Initially, promastigotes of Leishmania amazonensis were incubated with cell free conditioned medium of P. luminescens and parasite survival was monitored. Different pre-treatments of the conditioned medium revealed that the leishmanicidal activity is due to a secreted peptide smaller than 3 kDa. The Photorhabdus-derived leishmanicidal toxin (PLT) was enriched from conditioned medium and its effect on mitochondrial membrane potential of promastigotes, was determined. Moreover, the biological activity of PLT against amastigotes was evaluated. PLT inhibited the parasite growth and showed significant leishmanicidal activity against promastigote and amastigotes of L. amazonensis. PLT also caused mitochondrial dysfunction in parasites, but low toxicity to mammalian cell and human erythrocytes. Moreover, the anti-amastigote activity was independent of nitric oxide production. In summary, our results highlight that P. luminescens secretes Leishmania-toxic peptide(s) that are promising novel drugs for therapy against leishmaniasis.
Topics: Animals; Culture Media, Conditioned; Drug Discovery; Erythrocytes; Humans; Immunologic Factors; Leishmania mexicana; Macrophages; Membrane Potential, Mitochondrial; Mice; Mice, Inbred BALB C; Mitochondria; Nitric Oxide; Peptides; Photorhabdus; Secondary Metabolism
PubMed: 29157317
DOI: 10.1017/S0031182017002001 -
Current Topics in Microbiology and... 2017Although the first natural products (NP) from Photorhabdus and Xenorhabdus bacteria have been known now for almost 30 years, a huge variety of new compounds have been...
Although the first natural products (NP) from Photorhabdus and Xenorhabdus bacteria have been known now for almost 30 years, a huge variety of new compounds have been identified in the last 5-10 years, mainly due to the application of modern mass spectrometry. Additionally, application of molecular methods that allow the activation of NP production in several different strains as well as efficient heterologous expression methods have led to the production and validation of many new compounds. In this chapter we discuss the benefit of using Photorhabdus as a model system for microbial chemical ecology. We also examine non-ribosomal peptide synthetases as the most important pathway for NP production. Finally, we discuss the origin and function of all currently known NPs and the development of the molecular and chemical tools used to identify these NPs faster.
Topics: Biological Products; Photorhabdus; Xenorhabdus
PubMed: 28091935
DOI: 10.1007/82_2016_24 -
Microbes and Infection Mar 2010Photorhabdus asymbiotica is unique among the entomopathogenic bacteria of this genus in also being able to infect humans, leading to its isolation from some clinical... (Review)
Review
Photorhabdus asymbiotica is unique among the entomopathogenic bacteria of this genus in also being able to infect humans, leading to its isolation from some clinical samples. Recent comparative genomics data and the results of studies of interactions between bacteria and cells provide insight into the adaptation of this bacterium to its new niche, the human body.
Topics: Bacterial Proteins; Genome, Bacterial; Humans; Photorhabdus; Virulence; Virulence Factors
PubMed: 20034588
DOI: 10.1016/j.micinf.2009.12.003 -
Chembiochem : a European Journal of... Mar 2015Simple urea compounds ("phurealipids") have been identified from the entomopathogenic bacterium Photorhabdus luminescens, and their biosynthesis was elucidated. Very...
Simple urea compounds ("phurealipids") have been identified from the entomopathogenic bacterium Photorhabdus luminescens, and their biosynthesis was elucidated. Very similar analogues of these compounds have been previously developed as inhibitors of juvenile hormone epoxide hydrolase (JHEH), a key enzyme in insect development and growth. Phurealipids also inhibit JHEH, and therefore phurealipids might contribute to bacterial virulence.
Topics: Animals; Biological Products; Enzyme Inhibitors; Epoxide Hydrolases; Insecta; Photorhabdus; Structure-Activity Relationship; Urea
PubMed: 25711603
DOI: 10.1002/cbic.201402650 -
Research in Microbiology 2021Understanding the mode of action of pathogenic bacteria through in vitro studies can provide additional insight into their infection strategies. Here we have...
Understanding the mode of action of pathogenic bacteria through in vitro studies can provide additional insight into their infection strategies. Here we have characterized the effect of Photorhabdus luminescens and Photorhabdus asymbiotica on two distinct insect cell lines. We report that insect cell survival and metabolism as well as bacterial proliferation differ between infection with two Photorhabdus species. These findings reinforce the notion that P. luminescens and P. asymbiotica deploy diverse tactics to infect insect cells. This knowledge might lead to better appreciation of the interaction between pathogenic bacteria and different types of insect cells.
Topics: Animals; Bacterial Proteins; Cell Line; In Vitro Techniques; Insecta; Photorhabdus; Virulence
PubMed: 33794299
DOI: 10.1016/j.resmic.2021.103832 -
Cellular Microbiology Mar 2019Photorhabdus luminescens Tc toxins consist of the cell-binding component TcA, the linker component TcB, and the enzyme component TcC. TccC3, a specific isoform of TcC,...
Photorhabdus luminescens Tc toxins consist of the cell-binding component TcA, the linker component TcB, and the enzyme component TcC. TccC3, a specific isoform of TcC, ADP-ribosylates actin and causes redistribution of the actin cytoskeleton. TccC5, another isoform of TcC, ADP-ribosylates and activates Rho proteins. Here, we report that the proteasome inhibitor MG132 blocks the intoxication of cells by Tc toxin. The inhibitory effect of MG132 was not observed, when the ADP-ribosyltransferase domain of the TcC component was introduced into target cells by protective antigen, which is the binding and delivery component of anthrax toxin. Additionally, MG132 affected neither pore formation by TcA in artificial membranes nor binding of the toxin to cells. Furthermore, the in vitro ADP-ribosylation of actin by the enzyme domain of TccC3 was not affected by MG132. Similar to MG132, several calpain inhibitors blocked the action of the Tc toxin. Proteolytic cleavage of the binding component TcA induced by P. luminescens protease PrtA1 or by collagenase largely increased the toxicity of the Tc toxin. MG132 exhibited no inhibitory effect on the cleaved TcA component. Moreover, binding of TcA to target cells was largely increased after cleavage. The data indicate that Tc toxin is activated by proteolytic processing of the TcA component, resulting in increased receptor binding. Toxin processing is probably inhibited by MG132.
Topics: Bacterial Toxins; Cysteine Proteinase Inhibitors; Leupeptins; Peptide Hydrolases; Photorhabdus; Protein Binding; Proteolysis
PubMed: 30431706
DOI: 10.1111/cmi.12978 -
Applied Biochemistry and Biotechnology May 2020Photorhabdus luminescens is an entomopathogenic rod-shaped bacterium infected with insect nematodes of the Heterorhabditidae family. It kills insects through the...
Photorhabdus luminescens is an entomopathogenic rod-shaped bacterium infected with insect nematodes of the Heterorhabditidae family. It kills insects through the secretion of high molecular weight toxin complexes. In this study, Plutella xylostella larvae were orally administered P. luminescens for bioassay. After incubation in Luria-Bertani (LB) medium for a sufficiently long period, the mortality rates of P. xylostella observed after diluting the fermentation broth 50 times and diluting the supernatant 5 times were 18.89% and 91.11%, respectively. Retentates measuring more than 70 kDa showed 88% mortality after ultrafiltration (UF) membrane treatment. Thus, the supernatant of P. luminescens had insecticidal activity, and the main insecticidal toxin complexes had a molecular weight exceeding 70 kDa. The L (3) Taguchi orthogonal experimental optimized medium mode-predicted insecticidal activity levels were 84% and 119% in the 50-fold diluted fermentation broth and 5-fold diluted supernatant, respectively. Moreover, the insecticidal activity was improved to 92.2% in the 100-fold diluted fermentation broth and to 97.8% in the 10-fold diluted supernatant in the experiments. All combinations tested showed clear indications of lethality, including swelling, vesicle formation, cytoplasm vacuolization, and brush border membrane lysis. Thus, these results promote the use of P. luminescens 0805-P2R as a potent biopesticide to effectively control P. xylostella.
Topics: Animals; Bacterial Toxins; Insecticides; Moths; Photorhabdus
PubMed: 32100234
DOI: 10.1007/s12010-020-03289-8 -
BMC Genomics Jan 2008Photorhabdus luminescens and Yersinia enterocolitica are both enteric bacteria which are associated with insects. P. luminescens lives in symbiosis with soil nematodes... (Comparative Study)
Comparative Study Review
BACKGROUND
Photorhabdus luminescens and Yersinia enterocolitica are both enteric bacteria which are associated with insects. P. luminescens lives in symbiosis with soil nematodes and is highly pathogenic towards insects but not to humans. In contrast, Y. enterocolitica is widely found in the environment and mainly known to cause gastroenteritis in men, but has only recently been shown to be also toxic for insects. It is expected that both pathogens share an overlap of genetic determinants that play a role within the insect host.
RESULTS
A selective genome comparison was applied. Proteins belonging to the class of two-component regulatory systems, quorum sensing, universal stress proteins, and c-di-GMP signalling have been analysed. The interorganismic synopsis of selected regulatory systems uncovered common and distinct signalling mechanisms of both pathogens used for perception of signals within the insect host. Particularly, a new class of LuxR-like regulators was identified, which might be involved in detecting insect-specific molecules. In addition, the genetic overlap unravelled a two-component system that is unique for the genera Photorhabdus and Yersinia and is therefore suggested to play a major role in the pathogen-insect relationship. Our analysis also highlights factors of both pathogens that are expressed at low temperatures as encountered in insects in contrast to higher (body) temperature, providing evidence that temperature is a yet under-investigated environmental signal for bacterial adaptation to various hosts. Common degradative metabolic pathways are described that might be used to explore nutrients within the insect gut or hemolymph, thus enabling the proliferation of P. luminescens and Y. enterocolitica in their invertebrate hosts. A strikingly higher number of genes encoding insecticidal toxins and other virulence factors in P. luminescens compared to Y. enterocolitica correlates with the higher virulence of P. luminescens towards insects, and suggests a putative broader insect host spectrum of this pathogen.
CONCLUSION
A set of factors shared by the two pathogens was identified including those that are involved in the host infection process, in persistence within the insect, or in host exploitation. Some of them might have been selected during the association with insects and then adapted to pathogenesis in mammalian hosts.
Topics: Animals; Bacterial Proteins; Biological Evolution; Genes, Bacterial; Genome, Bacterial; Humans; Insecta; Photorhabdus; Signal Transduction; Species Specificity; Virulence; Yersinia enterocolitica
PubMed: 18221513
DOI: 10.1186/1471-2164-9-40