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

PLoS Pathog. 2024 Jun 4;20(6):e1012252. doi: 10.1371/journal.ppat.1012252. eCollection 2024 Jun.

Abstract

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 infection 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.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Drosophila melanogaster* / immunology
  • Drosophila melanogaster* / microbiology
  • Host-Pathogen Interactions / immunology
  • Immunity, Innate*
  • Pseudomonas Infections* / immunology
  • Pseudomonas Infections* / microbiology
  • Pseudomonas aeruginosa* / immunology
  • Pseudomonas aeruginosa* / pathogenicity
  • Virulence

Grants and funding

This work has been supported by Guangzhou Medical University, Université de Strasbourg, and CNRS, and also the China High-end Foreign Talent program (DF), the 111 Plan (Overseas Expertise Introduction Project for Discipline Innovation; D18010 to the Sino-French-Hoffmann Institute), the Incubation Project for Innovative Teams of Guangzhou Medical University (ZL, DF), the Open Project from State Key Laboratory of Respiratory Diseases (ZL, DF), the China Postdoctoral Foundation Project (Postdoctoral Innovation Talent Support Program of China 2017M612634 to JC), and the Special Fund for Scientific and Technological Innovation Strategy of Guangdong Province (2018A030310180 to JC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.