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Insight into the emerging insect to human pathogen Photorhabdus revealing geographic differences in immune cell
Max Addison1, Alexia Hapeshi1, Zi Xin Wong2
1Division of Biomedical Sciences, Warwick Medical School, University of Warwick, Coventry, United Kingdom.
Background:
Photorhabdus asymbiotica is a species of the insect pathogenic Photorhabdus genus that has been isolated as an etiological agent in human infections. Since then, multiple isolates have been identified worldwide; however, actual clinical infections have so far only been identified in North America, Australia, and Nepal. Previous research on the clinical isolates had shown that the strains differed in their behaviour when infecting cultured human cells.
Methods:
In this study, we investigate the differences between the pathogenic activities of P. asymbiotica isolates from different geographic locations. Pathogenicity was analysed using infection assays with both cultured cell lines (THP-1, CHO, and HEK cells) and primary immune cells, and peripheral blood mononuclear cells (PBMCs) isolated from human blood.
Results:
Here, we present the findings from the Australian (Kingscliff) and North American (ATCC43949) clinical isolates, and non-clinical soilborne nematode isolates from Thailand (PB68) and Northern Europe (HIT and JUN) of P. asymbiotica. We also show the first findings from a new clinical isolate of P. luminescens (Texas), the first non-asymbiotica species to cause a human infection, confirming its ability to infect and survive inside human immune cells.
Conclusion:
Here for the first time, we show how P. asymbiotica selectively infects certain immune cells while avoiding others and that infectivity varies depending on growth temperature. We also show that the tropism varies depending on the geographic location a strain is isolated from, with only the European HIT and JUN strains lack the ability to survive within mammalian cells in tissue culture.
Insights
Photorhabdus asymbiotica, a bacterium causing human infections, shows varied pathogenicity. Geographic location and temperature influence its ability to infect and survive within human immune cells, with European strains lacking mammalian cell infectivity.
Area of Science:
- Microbiology
- Infectious Diseases
- Bacterial Pathogenesis
Background:
- Photorhabdus asymbiotica, a known insect pathogen, has been identified as a cause of human infections globally.
- Clinical infections are primarily reported in North America, Australia, and Nepal, with prior studies noting strain-specific behaviors in human cell cultures.
Purpose of the Study:
- To investigate and compare the pathogenic activities of Photorhabdus asymbiotica isolates from diverse geographic origins.
- To analyze the differential infectivity and survival capabilities of these isolates within human cell lines and primary immune cells.
Main Methods:
- Infection assays were conducted using human cell lines (THP-1, CHO, HEK) and primary peripheral blood mononuclear cells (PBMCs).
- Pathogenicity was assessed across clinical isolates from Australia and North America, and non-clinical isolates from Thailand and Northern Europe.
- The study also included a new clinical isolate of Photorhabdus luminescens.
Main Results:
- Differences in pathogenic activity were observed among Photorhabdus asymbiotica isolates based on their geographic origin.
- The study identified selective immune cell targeting by P. asymbiotica, influenced by growth temperature.
- European strains (HIT, JUN) demonstrated an inability to survive within mammalian cells in tissue culture.
Conclusions:
- Photorhabdus asymbiotica exhibits variable tropism and infectivity towards human immune cells, contingent on geographic origin and environmental conditions.
- This variability highlights the complex host-pathogen interactions and potential for geographic-specific disease manifestations.
- The findings underscore the importance of considering isolate source in understanding P. asymbiotica pathogenesis.
