Insight into the emerging insect to human pathogen Photorhabdus revealing geographic differences in immune cell tropism

Abstract 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, based on the geographical site of isolation. In this study we investigate the differences between the pathogenic activities of P. asymbiotica isolates from different geographic locations. We present findings from the clinical isolates from Australia (Kingscliff) and North America (ATCC43949), and soil borne nematode isolates from Thailand (PB68) and Northern Europe non-clinical P. asymbiotica genospecies HIT and JUN. 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. Infection assays were done using both cultured cell lines (THP-1, CHO and HEK cells) and also primary immune cells, Peripheral Blood Mononuclear cells (PBMCs) isolated from human blood. 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 infected immune cells vary depending on the geographical location a strain is isolated from, and that the European HIT and JUN strains lack the ability to survive within mammalian cells in tissue culture.