Eukaryotic genes in vacuolar pathogens and symbionts - Implications for virulence, metabolism and ecology

Informations

Funding country

France

Acronym

EUGENPATH

URL

-

Start date

1/1/2013

End date

-

Budget

444,000 EUR

Fundings

Abstract

The phylogenetic diverse group of intracellular environmental bacteria comprises many human pathogens. Some of these resist degradation by free-living protozoa and – likely due to “training” in amoebae – also by macrophages. Macrophage resistance is a prerequisite for several life-threatening human respiratory diseases, including a severe pneumonia termed Legionnaires´ disease caused by Legionella spp., Q fever provoked by Coxiella burnetii, and respiratory diseases possibly caused by amoeba symbionts of the family Parachlamydiaceae. Intracellular bacterial pathogens and symbionts maintain intimate interactions with their eukaryotic hosts, which have been shaped by mutual trans-kingdom co-evolution over extended periods of time. To adapt to their intracellular niches, these bacteria acquired and functionally integrated genes from their unicellular hosts. Eukaryotic genes present in bacterial genomes, here termed “EUGENs”, represent a hallmark of intracellular bacteria, and are rarely if at all present in free-living bacteria. Thus, EUGENs are expected to define intracellular parasitic or symbiotic bacterial life styles, yet it is currently largely unknown to what extent and how. The genomes of members of the families Legionellaceae, Coxiellaceae and Parachlamydiaceae harbor dozens if not hundreds of EUGENs. Many EUGEN products are “effector” proteins that are translocated into host cells through dedicated type III or type IV secretion systems, and some have indeed been shown to interfere with host vesicle trafficking or signal transduction pathways. Yet, most EUGENs and their products have not been functionally studied on a molecular and cellular level. Here, we propose to analyze the role of distinct EUGENs in Legionella and Coxiella virulence, Protochlamydia symbiosis, and pathogen or symbiont metabolism. Furthermore, we will study for the first time the role of EUGENs in co-infection and bacterial ecology. By analyzing distinct groups of EUGENs and their products from different families of intracellular environmental bacteria, our studies will (i) provide mechanistic insights into parasitic and symbiotic processes, (ii) contribute to elucidating the relationship between parasitism and symbiosis, and (iii) establish a link between bacterial virulence or symbiosis and intracellular bacterial metabolism. These studies will reveal novel targets for anti-bacterial compounds and identify effectors useful as molecular probes and for vaccine development.