ABPs: diffusible antibacterial toxins secreted by and active against diverse gram-positive bacteria

Competition between organisms is a ubiquitous feature of life on Earth and a major driver of evolutionary innovation. As Earth's most diverse and abundant organisms, bacteria employ numerous strategies to inhibit the growth of competitors, ranging from the production of diffusible antibiotic metabolites to the secretion of sophisticated protein toxins. Although secreted antibacterial protein toxins have been extensively studied in gram-negative bacteria, analogous systems employed by gram-positive organisms remain comparatively poorly understood. Recent work has shed light on a widespread family of secreted protein toxins associated with co-secreted serine proteases that likely mediate interbacterial competition among gram-positive species. These systems, termed antibacterial protein (ABP) systems, consist of a secreted polymorphic toxin (AbpT), a co-secreted serine protease (AbpP), and a cytoplasmic immunity protein (AbpI). Following proteolytic processing, ABP toxins inhibit the growth of a remarkably diverse range of gram-positive bacteria spanning the phyla Bacillota and Actinomycetota. Existing evidence suggests that these proteins combine the properties of cationic antimicrobial peptides with those of classical polymorphic antibacterial toxins, potentially enabling toxin delivery into distantly related bacteria. In this review, we summarize the current understanding of the organization, mechanisms, and ecology of ABP systems; discuss major outstanding questions regarding toxin import and native biological function; and highlight opportunities for future mechanistic and biotechnological investigation in this emerging field.