Community composition and the environment modulate the population dynamics of type VI secretion in human gut bacteria

Abstract

Understanding the relationship between the composition of the human gut microbiota and the ecological forces shaping it is of high importance as progress towards therapeutic modulation of the microbiota advances. However, given the inaccessibility of the gastrointestinal tract, our knowledge of the biogeographical and ecological relationships between physically interacting taxa has been limited to date. It has been suggested that interbacterial antagonism plays an important role in gut community dynamics, but in practice the conditions under which antagonistic behavior is favored or disfavored by selection in the gut environment are not well known. Here, using phylogenomics of bacterial isolate genomes and analysis of infant and adult fecal metagenomes, we show that the contact-dependent type VI secretion system (T6SS) is repeatedly lost from the genomes of Bacteroides fragilis in adults compare to infants. Although this result implies a significant fitness cost to the T6SS, but we could not identify in vitro conditions under which such a cost manifests. Strikingly, however, experiments in mice illustrated that the B. fragilis T6SS can be favored or disfavored in the gut environment, depending on the strains and species in the surrounding community and their susceptibility to T6SS antagonism. We use a variety of ecological modeling techniques to explore the possible local community structuring conditions that could underlie the results of our larger scale phylogenomic and mouse gut experimental approaches. The models illustrate robustly that the pattern of local community structuring in space can modulate the extent of interactions between T6SS-producing, sensitive, and resistant bacteria, which in turn control the balance of fitness costs and benefits of performing contact-dependent antagonistic behavior. Taken together, our genomic analyses, in vivo studies, and ecological theory point toward new integrative models for interrogating the evolutionary dynamics of type VI secretion and other predominant modes of antagonistic interaction in diverse microbiomes.

Constitutive expression of the Type VI secretion system carries no measurable fitness cost inVibrio cholerae

“…Our work demonstrates that the fitness costs associated with constitutive expression of the Type VI Secretion System in V. cholerae are low, and will often be imperceptible to natural selection, even when considering the additional costs incurred by friendly fire. In contrast, recent work from others has shown that T6SS was strongly selected against within animal models [10]. Together, these results suggest that while the expression of the T6SS is not metabolically costly, it may nonetheless be costly to express in certain environments (e.g., through triggering host immune response [19], or via emergent consequences of changed ecological dynamics).…”

“…Our work demonstrates that the fitness costs associated with constitutive expression of the Type VI Secretion System in V. cholerae are low, and will often be imperceptible to natural selection, even when considering the additional costs incurred by friendly fire. In contrast, recent work from others has shown that T6SS was strongly selected against within animal models [10].…”

“…Given its hypothesized multi-megadalton size, complexity, and conservative developmental regulation, prior work has inferred that the T6SS must be metabolically costly to maintain and utilize [2, 4, 8, 9]. However, recent work attempting to measure the fitness cost of T6SS expression has found no detectable effect during a single 24 hour growth curve [10, 11]. Single-day growth curves have a relatively low sensitivity, however, as they can only measure competition outcomes over a limited number of generations, and are thus ineffective for measuring traits with a small impact on fitness [12].…”

Microbial collaborations and conflicts: unraveling interactions in the gut ecosystem

“… 29 In the mouse gut, the abundance of T6SS producers will increase while competing with sensitive competitors and significantly decrease if co-existent with resistant or non-interactive strangers. 35 These findings suggest that GA3 T6SS-dependent competition mechanism within a microbial community is intricate and heavily relies on the surrounding microbial lineages inhabiting the same ecological niches, as well as their sensitivity to T6SS antagonistic actions ( Figure 1 ). A genomic and metagenomic data based study indicated that GA2 and GA1 T6SS are widespread in Bacteroidales isolated from gut but absent in bacteria isolated from oral cavity or vagina, suggesting fitness advantage conferred by T6SS in gut environment 36 .…”

Mechanism of bacterial predation via ixotrophy

“…The incentive for bacteria to evolve such a genomic switch, could be the possibility to deactivate the expression of dispensable and energy-costly molecular machineries. Recent studies on Vibrio, Pseudomonas, and Bacteroides strains suggest that T6SS activity does in fact come with a fitness cost and it may be beneficial to regulate its activity (Drebes Dörr et al, 2022;Septer et al, 2023;Perault et al, 2020;Robitaille et al, 2023).…”