From Insect to Man: Photorhabdus Sheds Light on the Emergence of Human Pathogenicity

Abstract

Photorhabdus are highly effective insect pathogenic bacteria that exist in a mutualistic relationship with Heterorhabditid nematodes. Unlike other members of the genus, Photorhabdus asymbiotica can also infect humans. Most Photorhabdus cannot replicate above 34°C, limiting their host-range to poikilothermic invertebrates. In contrast, P. asymbiotica must necessarily be able to replicate at 37°C or above. Many well-studied mammalian pathogens use the elevated temperature of their host as a signal to regulate the necessary changes in gene expression required for infection. Here we use RNA-seq, proteomics and phenotype microarrays to examine temperature dependent differences in transcription, translation and phenotype of P. asymbiotica at 28°C versus 37°C, relevant to the insect or human hosts respectively. Our findings reveal relatively few temperature dependant differences in gene expression. There is however a striking difference in metabolism at 37°C, with a significant reduction in the range of carbon and nitrogen sources that otherwise support respiration at 28°C. We propose that the key adaptation that enables P. asymbiotica to infect humans is to aggressively acquire amino acids, peptides and other nutrients from the human host, employing a so called “nutritional virulence” strategy. This would simultaneously cripple the host immune response while providing nutrients sufficient for reproduction. This might explain the severity of ulcerated lesions observed in clinical cases of Photorhabdosis. Furthermore, while P. asymbiotica can invade mammalian cells they must also resist immediate killing by humoral immunity components in serum. We observed an increase in the production of the insect Phenol-oxidase inhibitor Rhabduscin normally deployed to inhibit the melanisation immune cascade. Crucially we demonstrated this molecule also facilitates protection against killing by the alternative human complement pathway.

Novelties in Pest Control by Entomopathogenic and Mollusc- Parasitic Nematodes

“…Ten years later, these clinical strains have been described as P. asymbiotica [123]. Mulley et al [124] demonstrated that during a human infection, P. asymbiotica aggressively acquires amino acids, peptides and other nutrients from the human host, employing a so-called 'nutritional virulence' strategy. The authors further revealed that, interestingly, an insect Phenol-oxidase inhibitor Rhabduscin protects P. asymbiotica against the human complement pathway.…”

Characterization of novel bangle lectin from Photorhabdus asymbiotica with dual sugar-binding specificity and its effect on host immunity

“…asymbiotica employs a so-called “nutritional virulence” strategy—it aggressively acquires amino acids, peptides and other nutrients from the host [ 5 ]. Previous studies revealed that many of the cytotoxins and virulence factors produced by Photorhabdus are equally effective against both insect and mammalian immune defence mechanisms [ 5 , 11 ]. The treatment of reported cases has required extensive antibiotic intervention with relapses in many cases [ 1 , 4 ].…”

“…asymbiotica a potentially more dangerous pathogen [ 15 ]. There is also a close phylogenetic relation to Yersinia pestis , a cause of plague, and the parallel between their behaviour is noteworthy [ 3 , 5 ].…”

Evolution and taxonomy of nematode-associated entomopathogenic bacteria of the genera Xenorhabdus and Photorhabdus: an overview

“…Current evidence suggests that the switch of these bacteria from nematodes to humans was facilitated by virulence genes (necessary for insect host infection) already present in the genome, as well as additional virulence factors (appropriate for infection of mammalian cells) acquired by horizontal transfer from other human pathogens (Hapeshi and Waterfield 2017). Unlike other species of the genus Photorhabdus, P. asymbiotica and P. australis can grow at 37°C, undergoing the metabolic shift to adapt their metabolisms to the mammalian host (Mulley et al 2015). Despite the considerable effort, the mechanisms of transmission of Photorhabdus bacteria to the human body are still unclear.…”