The endosymbiont increases resistance to pathogens by enhancing iron sequestration and melanization.

Unlabelled: Facultative endosymbiotic bacteria, such as and species, are commonly found in association with insects and can dramatically alter their host physiology. Many endosymbionts are defensive and protect their hosts against parasites or pathogens. Despite the widespread nature of defensive insect symbioses and their importance for the ecology and evolution of insects, the mechanisms of symbiont-mediated host protection remain poorly characterized. Here, we utilized the fruit fly and its facultative endosymbiont to characterize the mechanisms underlying symbiont-mediated host protection against bacterial and fungal pathogens. Our results indicate a variable effect of on infection outcome, with endosymbiont-harboring flies being more resistant to , and but more sensitive or as sensitive as endosymbiont-free flies to the infections with species. Further focusing on the protective effect, we identified Transferrin-mediated iron sequestration induced by as being crucial for the defense against and . In the case of , enhanced melanization in -harboring flies plays a major role in protection. Both iron sequestration and melanization induced by require the host immune sensor protease Persephone, suggesting a role of proteases secreted by the symbiont in the activation of host defense reactions. Hence, our work reveals a broader defensive range of than previously appreciated and adds nutritional immunity and melanization to the defensive arsenal of symbionts.

Importance: Defensive endosymbiotic bacteria conferring protection to their hosts against parasites and pathogens are widespread in insect populations. However, the mechanisms by which most symbionts confer protection are not fully understood. Here, we studied the mechanisms of protection against bacterial and fungal pathogens mediated by the endosymbiont . We demonstrate that besides the previously described protection against wasps and nematodes, also confers increased resistance to pathogenic bacteria and fungi. We identified -induced iron sequestration and melanization as key defense mechanisms. Our work broadens the known defense spectrum of and reveals a previously unappreciated role of melanization and iron sequestration in endosymbiont-mediated host protection. We propose that the mechanisms we have identified here may be of broader significance and could apply to other endosymbionts, particularly to , and potentially explain their protective properties.