A specific innate immune response silences the virulence of Pseudomonas aeruginosa in a latent infection model in the Drosophila melanogaster host.

Microbial pathogenicity often depends on the route of infection. For instance, P. aeruginosa or S. marcescens cause acute systemic infections when low numbers of bacteria are injected into D. melanogaster flies whereas flies succumb much slower to the continuous ingestion of these pathogens, even though both manage to escape from the gut compartment and reach the hemocoel. Here, we have developed a latent P. aeruginosa infection model by feeding flies on the bacteria for a short period. The bacteria stably colonize internal tissues yet hardly cause any damage since latently-infected flies live almost as long as noninfected control flies. The apparently dormant bacteria display particular characteristics in terms of bacterial colony morphology, composition of the outer cell wall, and motility. The virulence of these bacteria can however be reactivated upon wounding the host. We show that melanization but not the cellular or the systemic humoral response is the predominant host defense that establishes latency and may coerce the bacteria to a dormant state. In addition, the lasting activation of the melanization responses in latently-infected flies provides a degree of protection to the host against a secondary fungal infection. Latent infections by an ingested pathogen protects against a variety of homologous or heterologous systemic secondary infectious challenges, a situation previously described for the endosymbiotic Wolbachia bacteria, a guard against viral infections. Author summary: Environmentally ubiquitous bacteria have acquired extensive abilities to adapt to variable environments, bestowing to some of them the potential to become opportunistic pathogens. This may translate into distinct infection modes according to the route of entry. Whereas Pseudomonas aeruginosa is considered to have two major modes of infection, acute by planktonic cells or chronic through the establishment of biofilms, we report here a novel type of infection whereby ingested bacteria escape from the digestive tract and silently colonize tissues as single cells without strongly affecting the lifespan of the Drosophila host. The bacteria appear to be dormant, a feature shared with persister cells that elude the action of antibiotics. They are characterized by distinct bacterial and colony morphologies, cell surface and motility properties. Their virulence program can nevertheless be reactivated spontaneously or upon injury. We also report that an important host defense of invertebrates, melanization, is activated upon escape of the bacteria into the internal milieu. This activation not only promotes the dormancy of the colonizing bacteria but also protects the host to some degree against secondary infections. As P. aeruginosa is a member of the microbiota of a sizable fraction of human populations, these discoveries may become medically relevant. [ABSTRACT FROM AUTHOR]