Beyond genomics in Patescibacteria: A trove of unexplored biology packed into ultrasmall bacteria

Patescibacteria, also known as the Candidate Phyla Radiation, are a diverse clade of largely uncultivated, small bacteria that comprise a significant proportion of all bacterial diversity. The few members that have been cultivated exhibit a fascinating life cycle in which they grow as obligate epibionts on the surface of host bacteria. In this Perspective, we make the case that the study of these unique, divergent, and poorly characterized organisms represents an exciting frontier in microbiology. This burgeoning field has already achieved several critical breakthroughs, including metagenomic sequence-based reconstructions of the metabolic and biosynthetic capabilities of diverse Patescibacteria and the development of generalizable strategies for their cultivation and genetic manipulation. We argue these that advances, among others, should pave the way toward a molecular understanding of the complex interactions that undoubtedly underpin the relationship between Patescibacteria and their hosts.