Biology subjects

Coyte, K. Z.

Publications and source records attributed to Coyte, K. Z..

5 recordsLinked to original sources

bioRxiv2026

Paired sequencing of IgA-bound bacteria reveals widespread associations between adaptive immunity and gut microbiome gene expression.

Immunoglobulin A (IgA) is the most abundant antibody within the mammalian gut, where it binds to both pathogenic and commensal microbes. Despite its prevalence, the impact of IgA upon the biology and behavior of individual microbes remains poorly understood. Here we present Paired Immunoglobulin Sequencing (PIg-seq), a high-throughput method to identify IgA-associated changes in bacterial gene expression. Using PIg-seq we uncover widespread, and in many cases previously unrecognized, transcriptional responses associated with IgA-binding within the mouse gut. While many of these associations are conserved across diverse bacterial lineages, others vary dramatically even between closely related strains, revealing striking strain-level heterogeneity. Most notably, IgA binding is associated with altered expression of bacterial conjugation genes, and multiple prophages, suggesting an exciting link between adaptive immunity and horizontal gene transfer. Together, our findings establish IgA as a key regulator of microbial behavior, with potential consequences for both the ecology and the evolution of the gut microbiome.

microbiology↗

bioRxiv2024

Multiplicity of Type 6 Secretion System toxins limits the evolution of resistance

The bacterial Type 6 Secretion System (T6SS) is a toxin-injecting nanoweapon that mediates competition in plant- and animal-associated microbial communities. Bacteria can evolve de novo resistance against T6SS attacks, but resistance is far from universal in natural communities, suggesting key features of T6SS weaponry may act to limit its evolution. Here, we combine eco-evolutionary modelling and experimental evolution to examine how toxin type and multiplicity in Acinetobacter baylyi attackers shape resistance evolution in susceptible Escherichia coli competitors. In both our models and experiments, we find that combinations of multiple distinct toxins limit resistance evolution by creating genetic bottlenecks, driving resistant lineages extinct before they can reach high frequency. We also show that, paradoxically, single-toxin attackers often drive the evolution of cross-resistance, protecting bacteria against unfamiliar toxin combinations, even though such evolutionary pathways were inaccessible against multi-toxin attackers. Our findings indicate that, comparable to antimicrobial and anticancer combination therapies, multi-toxin T6SS arsenals function to limit resistance evolution in competing microbes. This helps us to understand why T6SSs remain widespread and effective weapons in microbial communities, and why many bacteria T6SS-armed encode functionally diverse anti-competitor toxins. SignificanceToxin secretion systems, such as T6SSs, are widely used by bacteria to inhibit competing microorganisms. Here, we show that the secretion of multiple toxins in combination can suppress the evolution of resistance to the T6SS, rationalising its continued widespread use across diverse communities. Our work shows that principles of combination therapy--well known in the context of antimicrobial, antiviral and anticancer therapies--also apply in the context of microbial warfare, helping to explain why many bacteria maintain diverse T6SS toxin arsenals. Resistance suppression is also a technologically useful property of T6SS toxin cocktails, which could be harnessed as part of future biocontrol or biotherapeutic applications, using live T6SS-armed bacteria to limit the growth of problem microorganisms.

microbiology↗

bioRxiv2023

What makes a temperate phage an effective bacterial weapon?

Temperate bacteriophages (phages) are common features of bacterial genomes and can act as self-amplifying biological weapons, killing susceptible competitors and thus increasing the fitness of their bacterial hosts (lysogens). Despite their prevalence, however, the key characteristics of an effective temperate phage weapon remain unclear. Here we use systematic mathematical analyses coupled with experimental tests to understand what makes an effective temperate phage weapon. We find that effectiveness is controlled by phage life history traits - in particular, the probability of lysis, and induction rate - but that the optimal combination of traits varies with the initial frequency of a lysogen within a population. As a consequence, certain phage weapons can be detrimental when their hosts are rare, yet beneficial when their hosts are common, while subtle changes in individual life history traits can completely reverse the impact of an individual phage weapon on lysogen fitness. We confirm key predictions of our model experimentally, using temperate phages isolated from the clinically relevant Liverpool Epidemic Strain of Pseudomonas aeruginosa. Through these experiments, we further demonstrate that nutrient availability can also play a critical role in driving frequency-dependent patterns in phage-mediated competition. Together, these findings highlight the complex and context-dependent nature of temperate phage weapons, and highlight the importance of both ecological and evolutionary processes in shaping microbial community dynamics more broadly. ImportanceTemperate bacteriophage - viruses that integrate within bacterial DNA - are incredibly common within bacterial genomes. These phages are thought to act as powerful self-amplifying weapons, allowing their bacterial hosts to kill nearby competitors and thus gain a fitness advantage within a given niche. But what makes an effective phage weapon? Here we first use a simple mathematical model to explore the factors determining phage weapon utility. Our models suggest that phage weapons are nuanced and context-dependent: an individual phage may be beneficial or costly depending upon tiny changes to how it behaves, or to the bacterial community in which it resides. We then confirm these mathematical predictions experimentally, using phage isolated from Cystic Fibrosis patients. But, in doing so, we also find that another factor - nutrient availability - plays a key role in shaping phage-mediated competition. Together our results provide new insights into how temperate phage modulate bacterial communities.

microbiology↗

bioRxiv2022

Horizontal gene transfer increases microbiome stability

Genes encoding resistance to stressors, such as antibiotics or environmental pollutants, are widespread across microbiomes, often encoded on mobile genetic elements. Yet despite their prevalence, the impact of resistance genes and their mobility upon the dynamics of microbial communities remains largely unknown. Here we develop eco-evolutionary theory to explore how resistance genes alter the stability of diverse microbiomes. We show that adding resistance genes to a microbiome typically increases its overall stability, particularly for mobile resistance genes with high transfer rates that efficiently spread resistance throughout the community. However, the impact of resistance genes upon the stability of individual taxa varies depending upon the mobility of the resistance gene and the network of ecological interactions within the community. Non-mobile resistance genes can benefit susceptible taxa in cooperative communities, yet damage those in competitive communities. Moreover, whilst the transfer of mobile resistance genes generally increases the stability of previously susceptible recipient taxa to perturbation, it can, counterintuitively, decrease the stability of the originally resistant donor species. We confirmed these theoretical predictions experimentally using competitive soil microcosm communities. Here the stability of a susceptible microbial community to perturbation was increased by adding mobile resistance genes encoded on conjugative plasmids but was decreased when these same genes were encoded on the chromosome. Together these findings highlight the importance of horizontal gene transfer in driving the eco-evolutionary dynamics of diverse microbiomes.

evolutionary biology↗

bioRxiv2020

Multi-kingdom quantitation reveals distinct ecological drivers of predictable early-life microbiome assembly

The infant gut microbiota develops remarkably predictably1-7, with pioneer species colonizing after birth, followed by an ordered succession of other microbes. This predictable assembly is vital to health8,9, yet the forces underlying it remain unknown. The environment, host and microbe-microbe interactions are all likely to shape microbiota dynamics, but in such a complex ecosystem identifying the specific role of any individual factor has remained a major challenge10-14. Here we use multi-kingdom absolute abundance quantitation, ecological modelling, and experimental validation to overcome this challenge. We quantify the absolute bacterial, fungal, and archaeal dynamics in a longitudinal cohort of 178 preterm infants. We uncover with exquisite precision microbial blooms and extinctions, and reveal an inverse correlation between bacterial and fungal loads the infant gut. We infer computationally then demonstrate experimentally in vitro and in vivo that predictable assembly dynamics are driven by directed, context-dependent interactions between microbes. Mirroring the dynamics of macroscopic ecosystems15-17, a late-arriving member,Klebsiella, exploits the pioneer,Staphylococcus, to gain a foothold within the gut. Remarkably, we find that interactions between kingdoms drive assembly, with a single fungal species,Candida albicans, inhibiting multiple dominant gut bacteria. Our work unveils the centrality of simple microbe-microbe interactions in shaping host-associated microbiota, a critical step towards targeted microbiota engineering.

microbiology↗