Biology subjects

Brockhurst, M.

Publications and source records attributed to Brockhurst, M..

At least 19 recordsLinked to original sources

bioRxiv2026

Engineering the Pseudomonas aeruginosa virus-isolation host viPAO1 reveals how host genetic barriers shape recoverable phage diversity

Cultured phage collections provide essential access to viral biology, but they capture only a small and biased fraction of natural phage diversity. Key barriers to diverse phage isolation are likely to include the prophages and defence systems present in the genomes of isolation hosts. Here, we show that removal of these host genetic barriers expands recoverable phage diversity in Pseudomonas aeruginosa. We constructed a series of progressively more permissive hosts derived from MPAO1 by sequentially deleting intracellular defence systems and resident prophages, culminating in viPAO1 (virus-isolation PAO1). Sequential removal of these barriers increased phage susceptibility, with Gabija and type I restriction-modification acting as major barriers to phage infection. In comparative isolation experiments, removal of intracellular barriers produced the largest increase in phage recovery, while additional receptor modification altered the composition of recovered phage subsets. viPAO1 also substantially increased recovery of phage contigs from environmental samples. Scaling this approach across 1090 clinical isolates enabled recovery of a curated collection of 69 individually purified temperate P. aeruginosa phages spanning 24 predicted genera, including 15 putative novel genera. Together, these findings demonstrate that removal of host genetic barriers to infection enhances recoverable phage diversity and establish permissive host engineering as a practical strategy for uncovering under-sampled regions of cultured phage diversity.

microbiology↗

bioRxiv2026

Multiple ecological and evolutionary mechanisms drive treatment-induced antibiotic resistance

The emergence of resistance within patients during antibiotic treatment is an important cause of treatment failure. However, the ecological and evolutionary mechanisms driving within-patient emergence remain poorly understood. Here, we analysed 24,478 Pseudomonas aeruginosa isolates sampled from 180 bronchiectasis patients during a clinical trial to understand how ciprofloxacin-resistant infections emerged over a one-year period of pulse-dosing. Pre-existing resistance predominated, accelerating resistance emergence relative to patients where resistance emerged by spontaneous mutation or strain immigration. Selective sweeps of costly mutations increased resistance over time in some patients, whereas in others oscillating resistance levels were driven by antibiotic treatment and resistance-growth trade-offs between genetically divergent subpopulations. Our findings show that infections under identical treatment follow diverse and sometimes complex ecological and evolutionary paths to antibiotic resistance, with implications for better predicting and managing treatment-induced antibiotic resistance.

evolutionary biology↗

bioRxiv2025

Intracellular niche specialisation drives evolutionary entrapment of endosymbiotic algae

Endosymbiosis underpins the evolution of complex life and the function of diverse ecosystems, but the mechanisms driving the origin and stability of endosymbiosis remain unclear. Fitness trade-offs between intracellular and extracellular niches could drive the emergence of stable endosymbiosis if adaptation to the intracellular niche reduces fitness in the extracellular niche, reinforcing endosymbiosis through niche specialisation by the endosymbiont. We tested this hypothesis by quantifying phenotypic divergence between endosymbiotic and free-living populations of a facultative algal endosymbiont along trait axes predicted to contrast between its intracellular and extracellular lifestyles. Consistent with endosymbiont specialisation, we observed strong divergence involving multiple traits between endosymbiotic and free-living populations. Specifically, endosymbionts showed convergent losses of multiple nitrogen metabolism pathways, increased export of maltose and glucose, increased sensitivity to acidification, higher and less variable photosynthetic efficiency, and reduced free-living growth rate. Intracellular environments are stable, safe from natural enemies, and come with a reliable supply of specific nutrients, but are acidic and place demands upon endosymbionts to provision their hosts; our data suggest that adapting to this niche is likely to reduce free-living growth and survival of endosymbionts. Our findings support fitness trade-offs between contrasting intracellular and extracellular environments as a mechanism stabilising endosymbiosis by driving evolutionary entrapment of niche-specialist endosymbionts.

evolutionary biology↗

bioRxiv2025

De novo genome sequence assembly of the model algal endosymbiont Micractinium conductrix derived from its host Paramecium bursaria 186b

Endosymbiosis is a major driver of evolutionary innovation and underpins the function of diverse ecosystems. The origins and evolution of endosymbiosis are challenging to study experimentally due to the short-lived culturability of many microbial strains derived from endosymbiotic interactions. The facultative endosymbiosis between the ciliate, Paramecium bursaria, and the green alga, Micractinium conductrix (Chlorellaceae, Trebouxiophyceae), is ecologically widespread and has emerged as a powerful lab-tractable model system. This endosymbiosis is founded upon a reciprocal nutrient exchange, but each of the species can be cultured independently enabling quantification of symbiotic fitness effects, new partnerships to be generated in the lab, and co-associations to be subject to experimental evolution. To date, evolve-and-resequence approaches have been limited due to a lack of high-quality genome assemblies enabling gene variants to be identified. Here, we report a near telomere-to-telomere genome assembly for M. conductrix 186b, using a range of sequencing technologies. Comparative analysis shows that this is one of the most complete Chlorellaceae algal genome assemblies available to date. To aid accurate gene calling and annotation we conducted both RNAseq and Iso-Seq transcriptome sequencing experiments. Collectively these omics datasets will facilitate: i) comparative genomics studies of endosymbiont evolution, ii) evolve-and-resequence experiments, iii) genome-scale metabolic modelling studies, and iv) identification of targets for genetic modification experiments and biotechnological applications. Significance statementEndosymbiosis, where one species, the endosymbiont, lives inside the cell of another species, the host, has played a key role in evolution of complex life. However, the origins and evolution of obligate endosymbioses are often challenging to study because the key events are hidden deep in evolutionary time. Facultative microbial endosymbioses, such as between the ciliate Paramecium bursaria and the green alga Micractinium conductrix, offer experimentally tractable model systems where interacting species can be grown independently or in association allowing studies of the origin, evolution and fitness effects of symbiosis. Here we report the genome sequence for M. conductrix from P. bursaria 186b, enabling genomic studies of the evolution of endosymbiosis and simplifying gene target acquisition for microbe engineering and biotechnological applications.

genomics↗

bioRxiv2025

Plasmid dependent phage eliminate pathogenic bacteria and antibiotic resistance plasmids from the chicken gut microbiome

Conjugative plasmids are a key reservoir of antimicrobial resistance (AMR) in commensal and pathogenic bacteria within the gut microbiome. Plasmid-dependent phage (PDPs) are a promising therapeutic option directly targeting AMR plasmids, but the efficacy of PDP therapy in vivo is poorly understood. Here, we show that treatment with the PRD1 phage eliminated Salmonella enterica carrying a broad-host range IncP AMR plasmid (RP4) from the chicken gut microbiome. Moreover, PRD1 treatment prevented the transfer of the RP4 plasmid to other members of the gut microbiome, whilst causing only minimal disruption to microbiome composition. Our results demonstrate that PDP therapy rapidly eliminates AMR from a natural gut microbiome by killing pathogenic bacteria and blocking AMR plasmid transmission to commensals, highlighting the conjugative pilus as a promising antimicrobial target.

microbiology↗

bioRxiv2025

Resistance mutation supply modulates the benefit of CRISPR immunity against virulent phages

Only a fraction of bacterial genomes encode CRISPR-Cas systems but the selective causes of this variation are unexplained. How naturally virulent bacteriophages (phages) select for CRISPR immunity has rarely been tested experimentally. Here, we show against a panel of genetically and functionally diverse virulent phages that CRISPR immunity was not universally beneficial, and its fitness effect varied strongly between phages in predictable ways. In addition to mechanisms known to alter the effectiveness of CRISPR immunity, such as encoding a matching spacer or a protective nuclear shell, we show that the fitness effect of CRISPR immunity negatively correlated with the probability of evolving receptor-based resistance to the phage via spontaneous mutation. Supply of resistance mutations differed strongly between very closely related lipopolysaccharide-binding phages and was associated with variation at the C-terminus of the tail fibre protein altering residues involved in hydrogen bonding and the predicted binding site. Our results show that CRISPR immunity is more beneficial against virulent phages that are harder to evolve resistance to via receptor mutations, suggesting that virulent phage community composition and diversity will be important drivers of the prevalence of CRISPR immunity.

microbiology↗

bioRxiv2024

Inflammation-like environments limit the loss of quorum sensing in Pseudomonas aeruginosa

Within-host environments are complex and multidimensional, making it challenging to link evolutionary responses of colonizing pathogens to causal selective drivers. Loss of quorum sensing (QS) via mutation of the master regulator, lasR, is a common adaptation of Pseudomonas aeruginosa during chronic infections. Here, we use experimental evolution in host-mimicking media to show that loss of QS is constrained by environmental factors associated with host inflammation. Specifically, environments combining oxidative stress and abundant free amino acids limited loss of QS, whereas QS loss was rapid in the absence of oxidative stress regardless of amino acids. Under oxidative stress, lasR mutations were contingent upon first decoupling regulation of oxidative stress responses from QS via mutations in the promoter region of the primary catalase, katA, or in the oxidative stress regulator, oxyR, enabling maintenance of oxidative stress tolerance. Together, our findings suggest that host inflammatory responses likely delay the loss of QS whilst colonizers undergo stepwise evolution, first adapting to survive lethal stressors before responding to other nutritional selective drivers that favour loss of QS.

evolutionary biology↗

bioRxiv2024

Genetic bioaugmentation-mediated bioremediation of terephthalate in soil microcosms using an engineered environmental plasmid

Harnessing in situ microbial communities to clean-up polluted natural environments is a potentially efficient means of bioremediation, but often the necessary genes to breakdown pollutants are missing. Genetic bioaugmentation, whereby the required genes are delivered to resident bacteria via horizonal gene transfer, offers a promising solution to this problem. Here we engineered a conjugative plasmid previously isolated from soil, pQBR57, to carry a synthetic set of genes allowing bacteria to consume terephthalate, a chemical component of plastics commonly released during their manufacture and breakdown. Our engineered plasmid caused a low fitness cost and was stably maintained in terephthalate contaminated soil by the bacterium P. putida. Plasmid carriers efficiently bioremediated contaminated soil, achieving complete breakdown of 3.2 mg/g of terephthalate within 8 days. The engineered plasmid horizontally transferred the synthetic operon to P. fluorescens in situ, and the resulting transconjugants degraded 10 mM terephthalate during a 180-hour incubation. Our findings show that environmental plasmids carrying synthetic catabolic operons can be useful tools for in situ engineering of microbial communities to perform clean-up even of complex environments like soil.

synthetic biology↗

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

Multidrug resistance plasmids commonly reprogramme expression of metabolic genes in Escherichia coli

Multidrug resistant Escherichia coli is a leading cause of global mortality. Transfer of plasmids carrying genes encoding beta-lactamases, carbapenamases, and colistin resistance genes between lineages is driving the rising rates of hard to treat nosocomial and community infections. Multidrug resistance (MDR) plasmid acquisition commonly causes transcriptional disruption, and whilst a number of studies have shown strain-specific fitness and transcriptional effects of an MDR plasmid across diverse bacterial lineages, fewer studies have compared impacts of different MDR plasmids in a common bacterial host. As such, our ability to predict which MDR plasmids are the most likely to be maintained and spread in bacterial populations is limited. Here, we introduced eight diverse MDR plasmids encoding resistances against a range of clinically important antibiotics into E. coli K-12 MG1655 and measured their fitness costs and transcriptional impacts. The scale of the transcriptional responses varied substantially between plasmids, ranging from >650 to <20 chromosomal genes being differentially expressed. However, neither the scale of regulatory disruption nor the plasmid size correlated with the magnitude of the plasmid fitness cost, which also varied between plasmids. The identities of differentially expressed genes varied among plasmids, although expression of certain metabolic genes and functions were convergently affected by multiple plasmids, including the downregulation of genes involved in L-methionine transport and metabolism. Our data show the complexity of interaction between host genetic background and plasmid genetic background in determining the impact of MDR plasmid acquisition on E. coli. ImportanceThe increase of infections that are resistant to multiple classes of antibiotics, including those isolates that carry carbapenamases, beta-lactamases, and colistin resistance genes, is of global concern. Many of these resistances are spread by conjugative plasmids. Understanding more about how an isolate responds to an incoming plasmid that encodes antibiotic resistance will provide information that could be used to predict the emergence of MDR lineages. Here, the identification of metabolic networks as being particularly sensitive to incoming plasmids suggests possible targets for reducing plasmid transfer.

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

Compensatory mutations reducing the fitness cost of plasmid carriage occur in plant rhizosphere communities

Plasmids drive bacterial evolutionary innovation by transferring ecologically important functions between lineages, but acquiring a plasmid often comes at a fitness cost to the host cell. Compensatory mutations, which ameliorate the cost of plasmid carriage, promote plasmid maintenance in simplified laboratory media across diverse plasmid-host associations. Whether such compensatory evolution can occur in more complex communities inhabiting natural environmental niches where evolutionary paths may be more constrained is, however, unclear. Here we show a substantial fitness cost of carrying the large conjugative plasmid pQBR103 in Pseudomonas fluorescens in the plant rhizosphere. This plasmid fitness cost could be ameliorated by compensatory mutations affecting the chromosomal global regulatory system gacA/gacS, which arose rapidly in plant rhizosphere communities and were exclusive to plasmid carriers. These findings expand our understanding of the importance of compensatory evolution in plasmid dynamics beyond simplified lab media. Compensatory mutations contribute to plasmid survival in bacterial populations living within complex microbial communities in their natural environmental niche.

microbiology↗

bioRxiv2022

Evolutionary responses to acquiring a multidrug resistance plasmid are dominated by metabolic functions across diverse Escherichia coli lineages

Multidrug resistance (MDR) plasmids drive the spread of antibiotic resistance between bacterial lineages. The immediate impact of MDR plasmid acquisition on fitness and cellular processes varies among bacterial lineages, but how the evolutionary processes enabling the genomic integration of MDR plasmids vary is less well understood, particularly in clinical pathogens. Using diverse Escherichia coli lineages experimentally evolved for [~]700 generations, we show that the evolutionary response to gaining the MDR plasmid pLL35 was dominated by chromosomal mutations affecting metabolic and regulatory functions, with both strain-specific and shared mutational targets. The expression of several of these functions, such as anaerobic metabolism, is known to be altered upon acquisition of pLL35. Interactions with resident mobile genetic elements, notably several IS-elements, potentiated parallel mutations, including insertions upstream of hns that were associated with its upregulation and the downregulation of the plasmid-encoded extended-spectrum beta-lactamase gene. Plasmid parallel mutations targeted conjugation-related genes, whose expression was also commonly downregulated in evolved clones. Beyond their role in horizontal gene transfer, plasmids can be an important selective force shaping the evolution of bacterial chromosomes and core cellular functions.

evolutionary biology↗

bioRxiv2022

Plasmid manipulation of bacterial behaviour through translational regulatory crosstalk

Beyond their role in horizontal gene transfer, conjugative plasmids commonly encode homologues of bacterial regulators. Known plasmid regulator homologues have highly targeted effects upon the transcription of specific bacterial traits. Here, we characterise a plasmid translational regulator, RsmQ, capable of taking global regulatory control in Pseudomonas fluorescens and causing a behavioural switch from motile to sessile lifestyle. RsmQ acts as a global regulator controlling the host proteome through direct interaction with host mRNAs and interference with the hosts translational regulatory network. This mRNA interference leads to largescale proteomic changes in metabolic genes, key regulators and genes involved in chemotaxis, thus controlling bacterial metabolism and motility. Moreover, comparative analyses found RsmQ on a large number of divergent plasmids isolated from multiple bacterial host taxa, suggesting the widespread importance of RsmQ for manipulating bacterial behaviour across clinical, environmental, and agricultural niches. RsmQ is a widespread plasmid global translational regulator primarily evolved for host chromosomal control to manipulate bacterial behaviour and lifestyle. Significance StatementPlasmids are recognised for their important role in bacterial evolution as drivers of horizontal gene transfer. Less well understood are the effects of plasmids upon bacterial behaviours by manipulating the expression of key bacterial phenotypes. Until now, examples of plasmid manipulation of their bacterial hosts were limited to highly targeted transcriptional control of a few related traits. In contrast, here we describe the first plasmid global translational regulator evolved to control the bacterial behavioural switch from a motile to a sessile lifestyle and bacterial metabolism, mediated through manipulation of the bacterial proteome. Moreover, this global translational regulator is common across divergent plasmids in a wide range of bacterial host taxa, suggesting that plasmids may commonly control bacterial lifestyle in the clinic, agricultural fields, and beyond.

microbiology↗

bioRxiv2021

Functional diversity increases the efficacy of phage combinations

Phage therapy is a promising alternative to traditional antibiotics for treating bacterial infections. Such phage-based therapeutics typically contain multiple phages, but how the efficacy of phage combinations scales with phage richness, identity and functional traits is unclear. Here, we experimentally tested the efficacy of 827 unique phage combinations ranging in phage richness from 1 to 12 phages. The efficacy of phage combinations increased with phage richness. However, complementarity between functionally diverse phages allowed efficacy to be maximised at lower levels of phage richness in functionally diverse combinations. These findings suggest that phage functional diversity is the key property of effective phage combinations, enabling the design of simple but effective phage therapies that overcome the practical and regulatory hurdles that limit development of more diverse phage therapy cocktails.

microbiology↗

bioRxiv2021

The dilution effect limits plasmid horizontal transmission in multispecies bacterial communities

By transferring ecologically important traits between species, plasmids drive genomic divergence and evolutionary innovation in their bacterial hosts. Bacterial communities are often diverse and contain multiple coexisting plasmids, but the dynamics of plasmids in multispecies communities are poorly understood. Here, we show, using experimental multispecies communities containing two plasmids, that bacterial diversity limits the horizontal transmission of plasmids due to the dilution effect; an epidemiological phenomenon whereby living alongside less proficient host species reduces the expected infection risk for a focal host species. In addition, plasmid horizontal transmission was also affected by plasmid diversity, such that the rate of plasmid conjugation was reduced from coinfected host cells carrying both plasmids. In diverse microbial communities, plasmid spread may be limited by the dilution effect and plasmid-plasmid interactions reducing the rate of horizontal transmission.

microbiology↗

bioRxiv2021

Plasmid fitness costs are caused by specific genetic conflicts

Plasmids play an important role in bacterial genome evolution by transferring genes between lineages. Fitness costs associated with plasmid acquisition are expected to be a barrier to gene exchange, but the causes of plasmid fitness costs are poorly understood. Single compensatory mutations are often sufficient to completely ameliorate plasmid fitness costs, suggesting that such costs are caused by specific genetic conflicts rather than generic properties of plasmids, such as their size, metabolic burden, or expression level. Here we show -- using a combination of experimental evolution, reverse genetics, and transcriptomics -- that fitness costs of two divergent large plasmids in Pseudomonas fluorescens are caused by inducing maladaptive expression of a chromosomal tailocin toxin operon. Mutations in single genes unrelated to the toxin operon, and located on either the chromosome or the plasmid, ameliorated the disruption associated with plasmid acquisition. We identify one of these compensatory loci, the chromosomal gene PFLU4242, as the key mediator of the fitness costs of both plasmids, with the other compensatory loci either reducing expression of this gene or mitigating its deleterious effects by upregulating a putative plasmid-borne ParAB operon. The chromosomal mobile genetic element Tn6291, which uses plasmids for transmission, remained upregulated even in compensated strains, suggesting that mobile genetic elements communicate through pathways independent of general physiological disruption. Plasmid fitness costs caused by specific genetic conflicts are unlikely to act as a long-term barrier to horizontal gene transfer due to their propensity for amelioration by single compensatory mutations, explaining why plasmids are so common in bacterial genomes.

microbiology↗

bioRxiv2021

HIGH VIRULENCE SELECTS FOR FAST HOST RESISTANCE EVOLUTION

Parasites and pathogens vary strikingly in their virulence and the resulting selection they impose on their hosts. While the evolution of different virulence levels is well studied, the evolution of host resistance in response to different virulence levels is less understood and as of now mainly based on observations and theoretical predictions with few experimental tests. Increased virulence can increase selection for host resistance evolution if resistance costs are outweighed by the benefits of avoiding infection. To test this, we experimentally evolved the bacterium Vibrio alginolyticus in the presence of two variants of the filamentous phage, VALG{Phi}8, that differ in their virulence. The bacterial host exhibited two alternative defence strategies against future phage infection: (1) super infection exclusion (SIE) whereby phage-infected cells were immune to subsequent infection at a cost of reduced growth, and (2) surface receptor mutations (SRM) in genes encoding the MSHA type-IV pilus providing resistance to infection by preventing phage attachment. While SIE emerged rapidly against both phages, SRM evolved faster against the high virulence compared to the low virulence phage. Using a mathematical model of our system we show that increasing virulence strengthens selection for SRM due to the higher costs of infection suffered by SIE immune hosts. In both the experiments and the model, higher levels of SRM in the host population drove more rapid phage extinction. Thus, by accelerating the evolution of host resistance, more virulent phages caused shorter epidemics.

evolutionary biology↗