Lipo-Chitooligosaccharides induce specialized fungal metabolite profiles that modulate bacterial growth

Authors: RUSH, TOMÁS - Oak Ridge National Laboratory; TANNOUS, JOANNA - Oak Ridge National Laboratory; LANE, MATTHEW - University Of Tennessee; GOPALAKRISHNAN MEENA, MURALIKRISHNAN - Oak Ridge National Laboratory; CARRELL, ALYSSA - Oak Ridge National Laboratory; GOLAN, JACOB - University Of Wisconsin; Drott, Milton; COTTAZ, SYLVAIN - Universite Grenoble Alpes; FORT, SÉBASTIEN - Universite Grenoble Alpes; ANÉ, JEAN-MICHEL - University Of Wisconsin; KELLER, NANCY - University Of Wisconsin; PELLETIER, DALE - Oak Ridge National Laboratory; JACOBSON, DANIEL - Oak Ridge National Laboratory; KAINER, DAVID - Oak Ridge National Laboratory; ABRAHAM, PAUL - Oak Ridge National Laboratory; GIANNONE, RICHARD - Oak Ridge National Laboratory; LABBE, JESSE - Oak Ridge National Laboratory

Submitted to: mSystems
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/2/2022
Publication Date: 12/1/2022
Citation: Rush, T.A., Tannous, J., Lane, M.J., Gopalakrishnan Meena, M., Carrell, A.A., Golan, J.J., Drott, M.T., Cottaz, S., Fort, S., Ané, J., Keller, N.P., Pelletier, D.A., Jacobson, D.A., Kainer, D., Abraham, P.E., Giannone, R.J., Labbe, J.L. 2022. Lipo-Chitooligosaccharides induce specialized fungal metabolite profiles that modulate bacterial growth. mSystems. 7(6). Article e01052-22. https://doi.org/10.1128/msystems.01052-22.
DOI: https://doi.org/10.1128/msystems.01052-22

Interpretive Summary: A set of compounds called Lipo-chitooligosaccharides (LCOs) have previously been shown to be used by fungi to form associations with plants. However, it has recently been shown that many fungi that do not form associations with plants also produce these compounds, raising questions about what role these compounds play in these organisms. Here we demonstrate for the first time that LCOs have important roles outside of forming associations with plants. Specifically we show that fungi produce new chemicals when subject to LCOs and that these compounds have various important activities including modulating how the fungus is able to fight off bacteria and grow. These results emphasize new opportunities to mine fungal genomes for useful pharmaceuticals and points to a new target to attack pathogenic fungi or to try and promote the growth of beneficial fungi.

Technical Abstract: Lipo-chitooligosaccharides (LCOs) are historically known for their role as microbial-derived signaling molecules that shape plant symbiosis. Recent studies suggest LCOs may have roles beyond plant symbiosis and more broadly act across other kingdoms of life. Our previous work has shown LCOs significantly affect physiology and transcriptome of Aspergillus fumigatus. In our effort to identify additional impacts these molecules might have on fungi, we are investigating the overall changes in A. fumigatus metabolomics in reponse to LCOs and their resulting influences on bacterial proliferation. Our metabolomic data revealed that the exogenous application of various type of LCOs to A. fumigatus resulted in significant shifts in its metabolic profile. Using network analyses, we highlight specific types of LCOs with the most significant effect on the abundance of known metabolites, many of which were observed to impact the growth rates of at least four different bacterial species representing five classes. These findings suggest that in addition to their role in symbiosis, LCOs exhibit significant effects on fungal metabolomes which, can consequently impact their competitive fitness with nearby microbes. This study demonstrates potential roles for LCOs as modulators of plant root microbiome dynamics and highlights the unexplored metabolomic richness that can be induced by these ubiquitously produced chemicals.