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?
