Review

Bacterial antagonism in host-associated microbial communities

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Science  21 Sep 2018:
Vol. 361, Issue 6408, eaat2456
DOI: 10.1126/science.aat2456

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Interspecies competition shapes communities

The gut microbiota of mammals is diverse and dynamic, and gut bacteria respond sensitively to diet and drug intake. Nevertheless, in a healthy adult, microbial community composition remains remarkably stable over time, despite being highly individual. García-Bayona and Comstock review the mechanisms that gut bacterial species use to jostle for space and resources and maintain their populations in the face of intense and varied competition. Bacteria have evolved a range of antibiotics, bacteriocins, toxins, and delivery devices to enable interspecies conflict. These interbacterial weapons possess a spectrum of specificities and range from those that target strains of their own species to broad-acting bacteriocides. This toxic armamentarium provides a valuable resource for potential therapeutic development.

Science, this issue p. eaat2456

Structured Abstract

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.

Intra- and interspecies antagonism—the example of Bacteroides species in the human gut.

Bacteroides fragilis and Bacteroides uniformis use MACPF (membrane attack complex/perforin) toxins—BSAP-1 and BSAP-2, respectively—for intraspecies killing. Producer strains carry a modified receptor [outer membrane protein (OMP) or lipopolysaccharide (LPS) glycan] that confers resistance to its cognate toxin. B. fragilis can also kill other B. fragilis strains and most gut Bacteroidales species via type VI secretion systems (T6SSs).

Abstract

Antagonistic interactions are abundant in microbial communities and contribute not only to the composition and relative proportions of their members but also to the longer-term stability of a community. This Review will largely focus on bacterial antagonism mediated by ribosomally synthesized peptides and proteins produced by members of host-associated microbial communities. We discuss recent findings on their diversity, functions, and ecological impacts. These systems play key roles in ecosystem defense, pathogen invasion, spatial segregation, and diversity but also confer indirect gains to the aggressor from products released by killed cells. Investigations into antagonistic bacterial interactions are important for our understanding of how the microbiota establish within hosts, influence health and disease, and offer insights into potential translational applications.

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