Publications by authors named "Nick Waterfield"

Photorhabdus asymbiotica is a species of bacterium that is pathogenic to humans whilst retaining the ability to infect insect hosts. Currently, there are two recognised subspecies, P. asymbiotica subsp.

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The largest continuous bacterial nonribosomal peptide synthetase discovered so far is described. It consists of 15 consecutive modules arising from an uninterrupted, fully functional gene in the entomopathogenic bacterium Photorhabdus luminescens. The identification of its cryptic biosynthesis product was achieved by using a combination of genome analysis, promoter exchange, isotopic labeling experiments, and total synthesis of a focused collection of peptide candidates.

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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.

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Discovery of new natural products by heterologous expression reaches its limits, especially when specific building blocks are missing in the heterologous host or the production medium. Here, we describe the insect-specific production of the new GameXPeptides E-H (5-8) from Photorhabdus luminescens TTO1, which can be produced heterologously from expression of the GameXPeptide synthetase GxpS only upon supplementation of the production media with the missing building blocks, and thus must be regarded as the true natural products under natural conditions.

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Mycotic aneurysms are a well-recognised complication of infective endocarditis. In contrast to many sequelae of endocarditis, they can present late in the course of the disease, despite adequate treatment. We discuss the case of an 82-year-old patient who was successfully treated for Enterococcus faecalis endocarditis, but presented late with a hypotensive collapse.

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Xenorhabdus and Photorhabdus spp. are bacterial symbionts of entomopathogenic nematodes (EPNs). In this study, we isolated and characterized Xenorhabdus and Photorhabdus spp.

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Many bacteria persist within phagocytes, deploying complex sets of tightly regulated virulence factors to manipulate and survive within host cells. So far, no single factor has been identified that is sufficient to allow intracellular persistence of an otherwise non-pathogenic bacterium. Here we report that the two-component KdpD/KdpE sensor kinase/response regulator of the insect and human pathogen Photorhabdus asymbiotica (Pa) is sufficient to allow a harmless laboratory strain of E.

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Photorhabdus spp., the only known bioluminescent terrestrial bacteria are well known for their symbiotic association with heterorhabditid nematodes. This association, along with their ability to kill insects, has aroused interest in the evolutionary relationships within this bacterial group.

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How does a quiescent symbiont of a nematode worm know when to turn nasty? Metabolic analysis and genetic knockouts confirm that model insect pathogens can sense L-proline in insect blood. This not only serves as a wake-up call, activating secondary metabolite virulence factors, but also provides an energy source for a metabolic shift appropriate for adaptation to the host environment.

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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.

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The toxin complex (Tc) genes were first identified in the insect pathogen Photorhabdus luminescens and encode approximately 1 MDa protein complexes which are toxic to insect pests. Subsequent genome sequencing projects have revealed the presence of tc orthologues in a range of bacterial pathogens known to be associated with insects. Interestingly, members of the mammalian-pathogenic yersiniae have also been shown to encode Tc orthologues.

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We describe the case of a 46-year-old female who presented with recurrent episodes of cerebrovascular events. She had an unremarkable family history and no risk factors for stroke, apart from smoking. A transthoracic echocardiogram with 'bubble' contrast was normal.

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Many members of the Yersinia genus encode homologues of insect toxins first observed in bacteria that are insect pathogens such as Photorhabdus, Xenorhabdus and Serratia entomophila. These bacteria secrete high molecular weight insecticidal toxins comprised of multiple protein subunits, termed the Toxin Complexes or Tc's. In Photorhabdus three distinct Tc subunits are required for full oral toxicity in insects, that include the [A], [B] and [C] types, although the exact stochiometry remains unclear.

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Although genome sequencing of microbial pathogens has shed light on the evolution of virulence, the drivers of the gain and loss of genes and of pathogenicity islands (gene clusters), which contribute to the emergence of new disease outbreaks, are unclear. Recent experiments with the bean pathogen Pseudomonas syringae pv. phaseolicola illustrate how exposure to resistance mechanisms acts as the driving force for genome reorganization.

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Photorhabdus asymbiotica is an emerging bacterial pathogen that causes locally invasive soft tissue and disseminated bacteremic infections in the United States and Australia. Although the source of infection was previously unknown, we report that the bacterium is found in a symbiotic association with an insect-pathogenic soil nematode of the genus Heterorhabditis.

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