Synthetic cells: Potential benefits and risks of interactions with commensal and pathogenic microorganisms

Abstract

Synthetic cells are shifting biology from the observation and modification of existing life toward the deliberate construction of cell-like systems. The term, however, includes two biologically different entities: bottom-up protocells assembled from nonliving molecular components and top-down cells whose natural genomes have been minimized, rewritten, or replaced. These two classes occupy the extremes of a much broader landscape of engineered living systems, one that also includes conventional bacteria, yeasts, and mammalian and immune cells carrying synthetic gene circuits, logic programs, and redesigned metabolic pathways. This Perspective is deliberately centered on the two extremes, because they bracket the range of biological autonomy and pose the sharpest contrast between a programmable chemical package and a self-replicating organism; the wider landscape is noted and is drawn upon throughout wherever it bears directly on interaction with microbial communities. Both approaches can clarify the minimum requirements for cellular organization, test hypotheses about the origin and evolution of life, expand biological chemistry, and support programmable sensing or therapy. Their most consequential future setting may not be an isolated laboratory vessel but a microbial ecosystem. Synthetic cells could detect pathogens, intercept virulence signals, deliver antimicrobials locally, support commensal organisms, or restore metabolic functions lost from a disturbed microbiome. The same capacity for molecular communication could also disrupt commensal networks, impose new selective pressures, transfer genetic information, provide exploitable metabolites, or behave unpredictably in complex communities. Because the deep architecture of life—an informational core, a bioenergetic engine, and a membrane-bounded interface under selection—is broadly conserved and governed by conformational matching, engineered constructs will be interpreted through the same molecular languages that natural organisms use to recognize nutrients, competitors, hosts, and threats. It is proposed that synthetic-cell safety should therefore be evaluated relationally: not only by what an engineered cell does alone, but by how natural microorganisms recognize, use, resist, modify, or reorganize around it. Throughout this Perspective, interactions are described as desired or unwanted relative to an explicitly stated design intention, rather than as beneficial or negative, because the same molecular event may be desirable in one ecological and clinical context and unwanted in another. The central challenge is to engineer compatibility where benefit is intended while preserving strong limits on persistence, evolution, and ecological reach.