Biology subjects

King, K. C.

Publications and source records attributed to King, K. C..

13 recordsLinked to original sources

bioRxiv2026

Pleiotropy links host axes of defense against a pathogen

Organisms face ubiquitous threats from pathogens, and in response hosts have evolved a cascade of defenses to avoid, resist, or tolerate infection. While these stepwise defenses may act independently, they can be pleiotropically linked via shared molecular mechanisms, regulation, and crosstalk. Here, we tested the extent to which pleiotropy shapes multiple axes of defense using knockouts of 16 single genes involved in innate immunity of Caenorhabditis elegans against the opportunistic bacterial pathogen Pseudomonas aeruginosa. Host genotype had variable effects on components of host defense. Traits such as infection-induced mortality and body size varied frequently across host genotypes, while behavioral avoidance, bacterial uptake, and susceptibility to bacterial colonization varied less frequently. Broadly, pleiotropy between defenses was common, driving patterns of variation that linked several traits together. However, important components of defense like mortality, avoidance, and susceptibility to colonization were more independent from one another. Our results show that pleiotropy between defenses can be common, highlighting the importance of moving beyond single phenotypes to understand multiple dimensions of host-pathogen interactions.

immunology↗

bioRxiv2026

Engineered phages evade the complete defense repertoire of highly phage-resistant MRSA clinical isolates

Phage therapy is a re-emerging approach for antimicrobial-resistant bacterial infections. However, the narrow host range of most phages remains a major barrier to the success and wider adoption of phage therapy. Although receptor incompatibility is often assumed to define phage-host specificity, we demonstrate that anti-phage defense systems are major determinants of host range in Staphylococcus aureus. Using a methicillin-resistant S. aureus (MRSA) clinical isolate as a model, we characterized the targeting profiles of its 15 defense systems and, for the first time, generated therapeutic phages that evade the full defense repertoire of a multi-phage-resistant strain. In particular, we show that defense-guided phage recombination is a powerful tool that leverages the modular design of phage genomes to replace targeted with untargeted components. Our holistic approach unveils defense synergies that constrain phage evasion and redundancies that allow the simultaneous evasion of multiple defenses. Finally, we show that an engineered phage cocktail prevents the emergence of phage resistance in the model and a second clinical strain with similar defenses. Our work provides a blueprint for translating our expanding knowledge of defense system identity and mechanism into the rational design of effective, next-generation phage therapeutics.

microbiology↗

bioRxiv2025

Coinfections dampen the effects of temperature on host-parasite interactions

Coinfections by multiple parasite species are widespread and modify disease outcomes. To what degree other forms of ecological complexity, such as environmental change, influence the impacts of coinfecting parasites on disease remains unclear. We exposed nematodes (Caenorhabditis elegans) to naturally coinfecting parasites (Leucobacter celer and musarum) at temperatures across the hosts thermal range. While we found that host mortality varied widely with temperature during single infections, coinfections buffered hosts against temperature-mediated variation via ongoing parasite competition. We extended our experiments with mathematical models indicating that changing virulence, rather than transmission, most plausibly underpins temperature-dependent host mortality. At moderate, but not extreme temperatures, we found coinfection continued to dampen mortality outcomes due to another source of host variation, genotypic susceptibility. Coinfection may provide a stabilizing effect on disease in a warming world - but this effect can falter when hosts are faced with multiple stressors.

ecology↗

bioRxiv2025

Competition constrains parasite adaptation to thermal heterogeneity

Temporal thermal heterogeneity is expected to favour intermediate, generalist phenotypes that can maintain growth across a broad thermal range but have sub-optimal growth at any single temperature. Yet, thermal variation typically occurs in the presence of additional selection pressures which may interact to constrain adaptation to temperature. We propagated competing lytic viral parasites (bacteriophages {phi}14-1 and {phi}LUZ19) of Pseudomonas aeruginosa under fluctuating temperatures (37-42{degrees}C) in monoculture and in co-culture. Without competition, fluctuating temperatures favoured intermediate thermal phenotypes in the phage {phi}14-1 and resulted in more variable evolutionary outcomes compared to static conditions. However, co-selection from fluctuating temperatures and competition led to restricted thermal adaptation, slower evolutionary rates, and fewer putative adaptive mutations in the {phi}LUZ19 competitor. Our study highlights the potential for reduced adaptive capacity in interacting communities amidst global climate change.

evolutionary biology↗

bioRxiv2025

Evolutionary rescue accelerates competitive exclusion in a parasite community

Environmental stress drives biodiversity loss by altering competitive hierarchies and pushing taxa towards extinction. Parasites and their communities are particularly vulnerable to stress due to environmental sensitivity of infection steps, variation in species tolerance during co-infections, and dependence on host fitness. Parasite populations might avoid extinction through evolutionary rescue - whereby rapid adaptation to stress enables persistence - but whether this process can preserve community diversity remains unclear. Here, we study the impact of evolutionary rescue in a simple parasite community by propagating populations of two viral parasites (bacteriophages {phi}14-1 and {phi}LUZ19) of Pseudomonas aeruginosa in monoculture and co-culture under two thermal conditions, a control temperature (37{degrees}C) and a high temperature that restricts {phi}14-1 growth (42{degrees}C). We show that evolutionary rescue of {phi}14-1 prevented extinction in monoculture. Rescue of this phage in co-culture made it a superior competitor, and it replaced {phi}LUZ19 as the dominant phage at high temperature. We determine that evolutionary rescue occurred through mutations in genes linked to attachment to bacterial hosts and within-host replication. We also show that competitive suppression by {phi}14-1 constrained {phi}LUZ19 molecular evolution. Our findings suggest that evolutionary rescue can prevent the extinction of some parasites, but may inadvertently destabilise the community and facilitate further biodiversity loss. This work underscores the need to take an eco-evolutionary approach to predict the responses of communities to global climate change.

evolutionary biology↗

bioRxiv2025

Evidence for Toxin-Encoding Coinfections Driving Intransitive Dynamics Between Allelopathic Phenotypes in Natural Yeast Populations

Competitive intransitivity -- non-hierarchical interactions, such as those exemplified by the rock-paper-scissors game, where no single competitor wins outright -- has been proposed as a key mechanism for maintaining biodiversity; however, empirical evidence supporting the importance of intransitivity remains limited. Natural populations of Saccharomyces cerevisiae often include strains harboring totivirus-satellite coinfections that encode a lethal toxic glycoprotein capable of eliminating competing yeast strains. Killer strains are sparsely distributed in natural populations, despite their competitive advantage. Yeast isolates occasionally exhibit toxin resistance, but it remains untested whether they can outcompete and replace killer strains. Similarly, the persistence of toxin-susceptible yeast is not well understood --particularly whether they can invade resistant populations in the absence of killers, thereby completing an intransitive loop. In a multi-year collection of yeast isolates from vineyards across New Zealand, we observed a near-complete disappearance of a previously common killer yeast genotype of S. cerevisiae over consecutive years. Using space-time-shift competition assays, we demonstrate that strains sympatric to this killer genotype were ubiquitously resistant, unlike the allopatric strains that were frequently eliminated in competition assays. Furthermore, the extinction of the focal killer genotype appears to have enabled the emergence of toxin-susceptible competitors in sites formerly occupied by the killer genotype. Our findings suggest that the competitive advantage of toxin production is evident in natural populations but appears to be eroded when resistance evolves in competitors of the focal killer genotype. We suggest that such killer-resistant-susceptible polymorphisms are being maintained by evolutionary dynamics akin to rock-paper-scissors-like intransitivity, driven by the invasion of susceptible strains after costly resistance has driven killer strains to extinction in natural populations, all being driven by toxin-encoding coinfections.

evolutionary biology↗

bioRxiv2025

Rising temperatures favour parasite virulence and parallel molecular evolution following a host jump

Climate change is facilitating the poleward emergence of parasites, increasing the risk of jumping into new animal species, including humans. Whether more virulent or transmissible variants will spread during these climate-driven outbreaks is unclear. We experimentally evolved a wild parasitic bacterium, across the thermal range (20-30{degrees}C) and extremes (35{degrees}C) of Cape Verde - the site of field collection - in a novel, temperate animal host. At the parasites typical warm environmental temperature, we found that virulence escalated across evolutionary time. Parasites evolved at hot temperatures, towards the limit of host-parasite survival, displayed a cryptic virulence boost, deadlier once infecting animals at cooler temperatures. Patterns of molecular evolution were constrained to parallel changes in fewer loci at extreme temperatures. Our findings suggest that rising temperatures will leave predictable phenotypic and genomic signatures on evolving parasites as they emerge with climate change.

evolutionary biology↗

bioRxiv2024

Within-host competition sparks pathogen molecular evolution and perpetual microbiota dysbiosis.

Pathogens newly invading a host must compete with resident microbiota. This within-host microbial warfare could lead to more severe disease outcomes or constrain the evolution of virulence. Using experimental evolution of a widespread pathogen (Staphylococcus aureus) and a native microbiota community in C. elegans nematode hosts, we show that a competitively superior pathogen displaced microbiota and reduced species richness, whilst maintaining virulence across generations. Conversely, pathogen populations and microbiota passaged separately caused more host harm relative to their respective ancestral controls. We find the evolved increase in virulence exhibited by pathogen populations passaged independently (compared to ancestral controls) was partly mediated by enhanced expression of the global virulence regulator agr and increased biofilm formation. Whole genome sequencing revealed shifts in the mode of selection from directional (on pathogens evolving alone) to fluctuating (on pathogens evolving with a host microbiota), with competitive interactions driving early diversification among pathogen populations. Metagenome sequencing of the evolved microbiota shows that evolution in infected hosts caused a significant reduction in community stability, along with restrictions on the co- existence of some species based on nutrient competition. Our study reveals how microbial competition during emerging infection determines the patterns and processes of evolution with major consequences for host health.

evolutionary biology↗

bioRxiv2024

Order among chaos: high throughput MYCroplanters can distinguish interacting drivers of host infection in a highly stochastic system

While microbiomes provide diverse benefits for their host, they are notoriously variable in structure and function. As a result, substantial experimental replication and scalability are required to identify the contributions of and interactions between microbiota, the host and the environment. Here, we describe a novel high throughput plant growth system (MYCroplanters) to test how multiple host, microbiota, and pathogen variables predict host health. Using an Arabidopsis-Pseudomonas host-microbiome-pathogen model, we found that host genotype and order of arrival predict competition outcome between strains in the rhizosphere, but pathogen and microbiota dose can overwhelm these effects. Regardless of host or inoculation conditions, final microbial community structure emerged as a consistent predictor of host health. We demonstrate that high-throughput tools like MYCroplanters can isolate interacting drivers of host health. Increasing the scale at which we can screen components of microbiome-mediated host benefits will facilitate building microbiome engineering solutions for medicine and agricultural applications.

ecology↗

bioRxiv2023

Genome dynamics across the evolutionary transition to endosymbiosis

Endosymbiosis - where a microbe lives and replicates within a host - is an important contributor to organismal function that has accelerated evolutionary innovations and catalysed the evolution of complex life. The evolutionary processes associated with transitions to endosymbiosis, however, are poorly understood. Here, we use comparative genomics of the genus Arsenophonus to reveal the complex processes that occur on evolution of an endosymbiotic lifestyle. We compared the genomes of 38 strains spanning diverse lifestyles from environmentally acquired infections to obligate inter-dependent endosymbionts. We observed recent endosymbionts had larger genome sizes than closely related environmentally acquired strains, consistent with evolutionary innovation and rapid gain of new function. Increased genome size was a consequence of prophage and plasmid acquisition including a cargo of type III effectors, and concomitant loss of CRISPR-Cas genome defence systems enabling mobile genetic element expansion. Persistent endosymbiosis was also associated with loss of type VI secretion, likely reflecting reduced microbe-microbe competition. Thereafter, the transition to stable endosymbiosis and vertical inheritance was associated with the expected relaxation of purifying selection, pseudogenisation of genes and reduction of metabolism, leading to genome reduction. However, reduced %GC that is typically considered a progressive linear process was observed only in obligate interdependent endosymbionts. We argue that a combination of the need for rapid horizontal gene transfer-mediated evolutionary innovation together with reduced phage predation in endosymbiotic niches drives loss of genome defence systems and rapid genome expansion upon adoption of endosymbiosis. These remodelling processes precede the reductive evolution traditionally associated with adaptation to endosymbiosis.

genomics↗

bioRxiv2022

Interactions between insect vectors and plant pathogens span the parasitism-mutualism continuum

Plants infected with vector-borne pathogens can suffer severe negative consequences, but the extent to which phytopathogens affect the fitness of their vector hosts remains unclear. Evolutionary theory predicts that selection on vector-borne pathogens should favour low virulence or mutualistic phenotypes in the vector, traits facilitating effective transmission between plant hosts. Here, we use a multivariate meta-analytic approach on 115 effect sizes across 34 unique plant-vector-pathogen systems to quantify the overall effect of phytopathogens on vector host fitness. In support of theoretical models, we report that phytopathogens overall have a neutral fitness effect on vector hosts. However, the range of possible fitness outcomes are diverse and span the parasitism-mutualism continuum. Contrary to previous predictions we found no evidence that transmission strategy, or the direct effects and indirect (plant-mediated) effects, of phytopathogens have divergent fitness outcomes for the vector. We discuss these findings in the context of plant - pathogen - vector ecology.

evolutionary biology↗

bioRxiv2019

Protective microbe enhances colonisation of a novel host species by modifying immune gene expression

Microbes that protect against infection inhabit hosts across the tree of life. It is unclear whether many protective microbes use or reduce the need for a host immune response, or how the immune system reacts when these microbes newly encounter a host species naturally and as part of a biocontrol strategy. We sequenced the transcriptome of a host (Caenorhabditis elegans) following its interaction with a non-native bacterium (Enterococcus faecalis) that has protective traits against the pathogen, Staphylococcus aureus. We show that microbe-mediated protection caused the differential expression of 1,557 genes, including the upregulation of many immune gene families conserved across the animal kingdom (e.g. lysozymes and c-type lectins). We found that this modulation of the hosts immune response was beneficial for both the protective microbe and the host. Given E. faecalis increased ability to resist lysozyme activity compared to S. aureus, our results indicate that the protective microbe could more easily invade and protect infected hosts by upregulating lysozyme genes. These results suggest that a protective microbe can exploit the host immune system even when introduced into a novel species. Microbes that protect via the host immune response in this way should favour continued investment into host immunity and avoid the evolution of host dependence. Author summaryOrganisms can be protected from infectious disease by the microbes they house. It is unclear, however, whether protective microbes affect the host immune response to infection, particularly in the early stages of symbiosis. In this study, we investigated the role of the host immune system in a novel protective interaction. We examined gene expression in a nematode after colonisation by a non-native microbe capable of suppressing the pathogen Staphylococcus aureus. The protective microbe altered the host immune response to infection in a way that it could exploit. By causing the host to increase the production of antimicrobials to which it itself is relatively resistant, the protective microbe was better able to colonise and defend infected hosts. These results indicate that protective microbes introduced into new host species can take advantage of the host immune system. Such a mechanism at the beginning of a protective symbiosis, formed either naturally or as part of a biocontrol strategy, could ensure continued investment in host-based defences over evolutionary time.

microbiology↗

bioRxiv2019

Diversity and disease: evidence for the monoculture effect beyond agricultural systems

Human activities are greatly reducing the genetic diversity of species worldwide. Given the prediction that parasites better exploit less diverse host populations, many species could be vulnerable to disease outbreaks. However, the widespread nature of the monoculture effect remains unclear outside agricultural systems. We conducted a meta-analysis of 22 studies, obtaining a total of 66 effect sizes, to directly test the biological conditions under which host genetic diversity limits infectious disease in populations. Overall, we found broad support for the monoculture effect across host and parasite species. The effect was independent of host range, host reproduction, parasite diversity, and the method by which the monoculture effect was recorded. Conversely, we found that parasite functional group, virulence, and empirical environment matters. Together, these results highlight the general susceptibility of genetically homogenous populations to infection. Consequently, this phenomenon could become increasingly common and alarming for at-risk populations due to human-driven declines in genetic diversity and shifts in parasite distributions.

ecology↗