Trade-off between virulence and immune evasion in the entomopathogenic bacteria Xenorhabdus nematophila

In the entomopathogenic bacterium Xenorhabdus nematophila the transcription factor Lrp regulates expression of factors required for pathogenesis and immune suppression in lepidopteran insects. Also, variation in Lrp protein levels leads to virulence modulation: low levels of Lrp are associated with a virulent phenotype and suppression of antimicrobial peptides (AMPs), while cells that lack Lrp or express high Lrp levels are attenuated and elicit expression of AMPs. The underlying causes of these variant host interaction phenotypes are not fully understood. Here we show that variations in virulence phenotypes are correlated with differential Lrp-dependent expression of virulence determinants and immunogenic molecules. Cells expressing high levels of Lrp produced the highest concentration of lipopolysaccharide (LPS) and were the most toxic to M. sexta larvae when compared to cells that lack Lrp or express low Lrp levels. To determine if heightened immunogenicity (e.g. due to expression of immunogenic LPS) impairs the ability of high Lrp bacteria to kill insects we suppressed immunity in insect larvae by co-injecting cells with benzylideneacetone, a known X. nematophila-produced immunosuppressive molecule. Chemical suppression of immunity enhanced the virulence of the X. nematophila cells expressing high levels of Lrp but not that of cells that lacked Lrp expression. Our data show that virulence attenuation in the X. nematophila delta Lrp is not due to its inability to suppress immunity, but likely due to decreased toxicity, while virulence attenuation of high Lrp cells is due to uncontrolled expression of immunogenic factors or increased sensitivity to insect immunity. Taken together, our data suggests that in vivo X. nematophila Lrp regulates the timing or levels of virulence factors that can also be immunogenic and that the outcome of infection is in part due to a trade-off between expression of these factors and immune evasion.