Why are archaea non-pathogenic? A comprehensive and genomics approach

Abstract

Pathogenicity, the ability to cause disease in a multicellular host, is observed throughout Bacteria. Yet, no archaeal pathogens have been documented. Proposed hypotheses suggest that archaea lack the metabolic lifestyle required for pathogenicity. However, to my knowledge, no comprehensive analyses have shown the metabolic lifestyle required by pathogens and whether archaea have this metabolic lifestyle. Here, we extracted available information about the environment, pathogen and metabolism status of 655 archaeal species and 8,893 bacterial strains from databases and article review to explore the association between metabolism, pathogenicity, and environments. First, we explicitly showed a Chemo-Organo-Heterotrophic (COH) metabolic lifestyle is the prerequisite for pathogenicity. Furthermore, we showed that metabolic lifestyles evolve slower than pathogenicity, suggesting that the slow evolution of metabolic lifestyles impedes the evolution of pathogenicity. Yet, some archaea are COH suggesting that some archaea have the metabolic prerequisite of pathogenicity. Therefore, we explored if the environment had constrained COH archaea from interacting with a host. We showed that COH archaea are associated with environments inhospitable for most hosts. In addition, we showed that host-associated archaea lack the metabolic prerequisite of pathogenicity. Therefore, archaea are non-pathogenic because host-associated archaea lack the metabolic prerequisite of pathogenicity. Our research has shifted our curiosity to a nuanced question: Why are host-associated archaea Non-COH?