Untargeted metabolomics studies employing NMR and LC–MS reveal metabolic coupling between Nanoarcheum equitans and its archaeal host Ignicoccus hospitalis
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Interspecies interactions are the basis of microbial community formation and infectious diseases. Systems biology enables the construction of complex models describing such interactions, leading to a better understanding of disease states and communities. However, before interactions between complex organisms can be understood, metabolic and energetic implications of simpler real-world host-microbe systems must be worked out. To this effect, untargeted metabolomics experiments were conducted and integrated with proteomics data to characterize key molecular-level interactions between two hyperthermophilic microbial species, both of which have reduced genomes. Metabolic changes and transfer of metabolites between the archaea Ignicoccus hospitalis and Nanoarcheum equitans were investigated using integrated LC–MS and NMR metabolomics. The study of such a system is challenging, as no genetic tools are available, growth in the laboratory is challenging, and mechanisms by which they interact are unknown. Together with information about relative enzyme levels obtained from shotgun proteomics, the metabolomics data provided useful insights into metabolic pathways and cellular networks of I. hospitalis that are impacted by the presence of N. equitans, including arginine, isoleucine, and CTP biosynthesis. On the organismal level, the data indicate that N. equitans exploits metabolites generated by I. hospitalis to satisfy its own metabolic needs. This finding is based on N. equitans’s consumption of a significant fraction of the metabolite pool in I. hospitalis that cannot solely be attributed to increased biomass production for N. equitans. Combining LC–MS and NMR metabolomics datasets improved coverage of the metabolome and enhanced the identification and quantitation of cellular metabolites.
KeywordsLC–MS and NMR Metabolomics Ignicoccus hospitalis-Nanoarcheum equitans Interspecies interactions Hyperthermophilic archea Systems biology
This research was supported by a Grant from the U.S. Department of Energy, Office of Biological and Environmental Research (DE-SC0006654). The NMR experiments were recorded at Montana State University on a DRX600 Bruker solution NMR spectrometer, purchased in part with funds from the NIH Shared Instrumentation Grant (SIG) (Grant Number 1S10-RR13878-01), and recently upgraded to an AVANCE III console and cryogenically cooled TCI probe (Grant Number 1S10-RR026659-01). The mass spectrometry facility at MSU receives funding from the Murdock Charitable Trust and NIH 5P20RR02437 of the CoBRE program. We thank Dr. Harald Huber (University of Regensburg, Germany) for providing a bioreactor sample of I. hospitalis-N. equitans used for initial methods development.
Conflict of interest
The authors declare no conflict of interest.
Compliance with ethical requirements
This article does not contain any studies with human or animal subjects.
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