Bacterial antagonism in host-associated microbial communities

BACKGROUND Microbial communities are ubiquitous on Earth. The microbiota of different habitats are diverse and have distinct functional traits, but there are common ecological principles that govern their composition. The ability of a microbe to compete with other members of its community for resources is paramount to its success. Competition through the production of molecules that harm other members, known as interference competition, is also important in the assembly and maintenance of microbial communities. As new technologies allow for more in-depth analyses of microbial communities and their genetic content, we are better able to identify new antimicrobial toxins and analyze the effects of their production. Here, we explore the range of antibacterial protein/peptide toxins and toxin-secretion systems, together with the fitness benefits they confer to the producing organisms. Because human-associated microbial communities have been intensely studied over the past decade, our focus is on the growing body of data regarding bacterial antagonism in these and other host-associated microbial communities. ADVANCES Studies continue to reveal the large arsenal of antibacterial peptides and proteins that bacteria produce and the secretion systems that they use to deliver these toxins to competing cells. Bacterially produced antimicrobial peptides and proteins are diverse in terms of their structures, cellular targets, mechanisms of action, and spatial range. Their antagonistic range also varies; some are limited to intraspecies killing, whereas others are able to kill across genera, families, and orders. Through a combination of mathematical modeling and experimental model systems, the ecological outcomes of bacterial antagonism are being elucidated. In vivo analyses in host models have shown that some antimicrobial toxins play a role in microbiota-mediated colonization resistance by preventing invasion of pathogens. Some pathogens, however, also use toxins to battle with the resident microbiota to invade an ecosystem and cause disease. Antagonism has also been shown to facilitate genome evolution; the DNA released from killed cells can be taken up and incorporated into the aggressor’s genome. In some cases, antagonism has been shown to increase rather than reduce microbial diversity, potentially through promotion of spatial segregation of competing strains, facilitating the exchange of signals and secreted products between related cells (kin). The factors that regulate the production and release of some antibacterial toxins are also becoming better understood. Studies are revealing that toxin producers respond to various environmental signals, including signals that indicate host occupancy, that nutrients are limiting, or that they may be attacked by other bacterial community members. OUTLOOK Although bacterial antagonism is an active area of research, we are still in the early stages of understanding the impacts of these interactions in natural community settings and how they influence the overall structure, dynamics, and composition of complex microbial communities. The rapid increase in the number of available metagenomic datasets derived from diverse microbial communities and the expanding capability to culture and genetically modify these organisms is allowing for the identification and characterization of new . The protective function of microbiota-produced toxins in warding off pathogens indicates a potential for applications in medical, agricultural, and other industrial settings. In addition, the inclusion of antibacterial toxins in genetically engineered bacteria (live biotherapeutics) may allow for specific targeting of harmful community members, including those involved in therapeutic failures, and may also allow a live biotherapeutic to compete with members of the microbiota to deliver various health-promoting functions.