Study of leaf endophytic fungi: Exploration and valorization of biosourCed Innovative antibacterial metaboLites – SECIL

The continued growth of the human population combined with several related factors such as growing international exchanges, climate changes, burst of resistant pathogens, increased livestock production, or increased immunodepressed population favour the emergence and re-emergence of many infectious diseases. It turns out that infectious pathogens may be more indomitable than one could imagine at first sight, and some authors postulate that humanity is on the verge of a post-antibiotic era. Even a well-reasoned use of antibiotic and antifungal compounds is insufficient, and new molecules and new concepts are necessary to manage microbial pathologies.

Molecules of natural origin are the source of a significant part of the drugs used in the clinics today. This is especially true for anti-infective agents. The most recent comprehensive survey on the origin of drugs by Newman and Cragg reported that drugs of natural origin and those based on natural product scaffolds represent 75% of the approved 104 new antibacterial chemical entities introduced in the period 1981-2010. This highlights the importance of natural products as a basis for new treatments for bacterial diseases. In the same time, all natural antibacterial agents developed for clinical use were from microorganisms, but the large majority of them were discovered as secondary metabolites of soil microbes. There are, however, other microbial communities that have never been mined for anti-infective compounds. These include isolated microbiomes, marine environments, and even niches in plants, insects and mammals. The focus on restricted, highly competitive, microbial communities should point out that the main role of antibiotic substances may be to perform microbial crosstalk to maintain, rather than disrupt, complex microbial populations. Moreover, endophytes have a significant impact on the way their hosts interact with pathogens, competitors, and herbivores.

We propose to investigate microbial crosstalk in plant leaf endophytes searching for antibacterial agents of a new and unique kind. We will undertake in depth investigation of two model systems, known for the longevity of their leaves or shoots, and in which we have recently discovered very diverse and unusual fungal communities: Astrocaryum sciophilum, a typical palm tree from the primary forest in French Guiana which seems to host a huge diversity of fungi a little bacteria, and Posidonia oceanica, a dominant herb of marine grassland from the Mediterranean which may be associated to highly specific marine fungi. With these two systems, we will address the following questions:

1. What are the diversity and the identity of foliar endophyte communities in the selected plant leaves? Are these ecosystems selecting a few fungal lineages and how far is competition shaping these communities?
2. What bioactive fungal metabolites will be mined in these systems and do these metabolites act on innovative bacterial targets?
3. Using metabolomic and genomic approaches in parallel, can we discover the molecular intermediates and genes involved in the biosynthesis of antibacterial fungal metabolites ?