Defense Heterogeneity in Host Populations Gives Rise to Pathogen Diversity.

AbstractHost organisms can harbor microbial symbionts that defend them from pathogen infection in addition to the resistance encoded by the host genome. Here, we investigated how variation in defenses, generated from host genetic background and symbiont presence, affects the emergence of pathogen genetic diversity across evolutionary time. We passaged the opportunistic pathogen Pseudomonas aeruginosa through populations of the nematode Caenorhabditis elegans varying in genetic-based defenses and prevalence of a protective symbiont. After 14 passages, we assessed the amount of genetic variation accumulated in evolved pathogen lineages. We found that diversity begets diversity. An overall greater level of pathogen whole-genome and per-gene genetic diversity was measured in pathogens evolved in mixed host populations compared with those evolved in host populations composed of one type of defense. Our findings directly demonstrate that symbiont-generated heterogeneity in host defense can be a significant contributor to pathogen genetic variation.

Impact of the COVID-19 pandemic on health-care use among patients with cancer in England, UK: a comprehensive phase-by-phase time-series analysis across attendance types for 38 cancers.

BACKGROUND: The COVID-19 pandemic resulted in the widespread disruption of cancer health provision services across the entirety of the cancer care pathway in the UK, from screening to treatment. The potential long-term health implications, including increased mortality for individuals who missed diagnoses or appointments, are concerning. However, the precise impact of lockdown policies on national cancer health service provision across diagnostic groups is understudied. We aimed to systematically evaluate changes in patterns of attendance for groups of individuals diagnosed with cancer, including the changes in attendance volume and consultation rates, stratified by both time-based exposures and by patient-based exposures and to better understand the impact of such changes on cancer-specific mortality. METHODS: In this retrospective, cross-sectional, phase-by-phase time-series analysis, by using primary care records linked to hospitals and the death registry from Jan 1, 1998, to June 17, 2021, we conducted descriptive analyses to quantify attendance changes for groups stratified by patient-based exposures (Index of Multiple Deprivation, ethnicity, age, comorbidity count, practice region, diagnosis time, and cancer subtype) across different phases of the COVID-19 pandemic in England, UK. In this study, we defined the phases of the COVID-19 pandemic as: pre-pandemic period (Jan 1, 2018, to March 22, 2020), lockdown 1 (March 23 to June 21, 2020), minimal restrictions (June 22 to Sept 20, 2020), lockdown 2 (Sept 21, 2020, to Jan 3, 2021), lockdown 3 (Jan 4 to March 21, 2021), and lockdown restrictions lifted (March 22 to March 31, 2021). In the analyses we examined changes in both attendance volume and consultation rate. We further compared changes in attendance trends to cancer-specific mortality trends. Finally, we conducted an interrupted time-series analysis with the lockdown on March 23, 2020, as the intervention point using an autoregressive integrated moving average model. FINDINGS: From 561 611 eligible individuals, 7 964 685 attendances were recorded. During the first lockdown, the median attendance volume decreased (-35·30% [IQR -36·10 to -34·25]) compared with the preceding pre-pandemic period, followed by a median change of 4·38% (2·66 to 5·15) during minimal restrictions. More drastic reductions in attendance volume were seen in the second (-48·71% [-49·54 to -48·26]) and third (-71·62% [-72·23 to -70·97]) lockdowns. These reductions were followed by a 4·48% (3·45 to 7·10) increase in attendance when lockdown restrictions were lifted. The median consultation rate change during the first lockdown was 31·32% (25·10 to 33·60), followed by a median change of -0·25% (-1·38 to 1·68) during minimal restrictions. The median consultation rate decreased in the second (-33·89% [-34·64 to -33·18]) and third (-4·98% [-5·71 to -4·00]) lockdowns, followed by a 416·16% increase (409·77 to 429·77) upon lifting of lockdown restrictions. Notably, across many weeks, a year-over-year decrease in weekly attendances corresponded with a year-over-year increase in cancer-specific mortality. Overall, the pandemic period revealed a statistically significant reduction in attendances for patients with cancer (lockdown 1 -24 070·19 attendances, p<0·0001; minimal restrictions -19 194·89 attendances, p<0·0001; lockdown 2 -31 311·28 attendances, p<0·0001; lockdown 3 -43 843·38 attendances, p<0·0001; and lockdown restrictions lifted -56 260·50 attendances, p<0·0001) compared with before the pandemic. INTERPRETATION: The UK's COVID-19 pandemic lockdown affected cancer health service access negatively. Many groups of individuals with cancer had declines in attendance volume and consultation rate across the phases of the pandemic. A decrease in attendances might lead to delays in cancer diagnoses, treatment, and follow-up, putting such groups of individuals at higher risk of negative health outcomes, such as cancer-specific mortality. We discuss the factors potentially responsible for explaining changes in service provision trends and provide insight to help inform clinical follow-up for groups of individuals at risk, alongside potential future policy changes in the care of such patients. FUNDING: Wellcome Trust, National Institute for Health Research University College London Hospitals Biomedical Research Centre, National Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, Academy of Medical Sciences, and the University College London Overseas Research Scholarship.

Warming alters life-history traits and competition in a phage community.

Host-parasite interactions are highly susceptible to changes in temperature due to mismatches in species thermal responses. In nature, parasites often exist in communities, and responses to temperature are expected to vary between host-parasite pairs. Temperature change thus has consequences for both host-parasite dynamics and parasite-parasite interactions. Here, we investigate the impact of warming (37°C, 40°C, and 42°C) on parasite life-history traits and competition using the opportunistic bacterial pathogen Pseudomonas aeruginosa (host) and a panel of three genetically diverse lytic bacteriophages (parasites). We show that phages vary in their responses to temperature. While 37°C and 40°C did not have a major effect on phage infectivity, infection by two phages was restricted at 42°C. This outcome was attributed to disruption of different phage life-history traits including host attachment and replication inside hosts. Furthermore, we show that temperature mediates competition between phages by altering their competitiveness. These results highlight phage trait variation across thermal regimes with the potential to drive community dynamics. Our results have important implications for eukaryotic viromes and the design of phage cocktail therapies.IMPORTANCEMammalian hosts often elevate their body temperatures through fevers to restrict the growth of bacterial infections. However, the extent to which fever temperatures affect the communities of phages with the ability to parasitize those bacteria remains unclear. In this study, we investigate the impact of warming across a fever temperature range (37°C, 40°C, and 42°C) on phage life-history traits and competition using a bacterium (host) and bacteriophage (parasite) system. We show that phages vary in their responses to temperature due to disruption of different phage life-history traits. Furthermore, we show that temperature can alter phage competitiveness and shape phage-phage competition outcomes. These results suggest that fever temperatures have the potential to restrict phage infectivity and drive phage community dynamics. We discuss implications for the role of temperature in shaping host-parasite interactions more widely.

The impacts of host association and perturbation on symbiont fitness.

Symbiosis can benefit hosts in numerous ways, but less is known about whether interactions with hosts benefit symbionts-the smaller species in the relationship. To determine the fitness impact of host association on symbionts in likely mutualisms, we conducted a meta-analysis across 91 unique host-symbiont pairings under a range of spatial and temporal contexts. Specifically, we assess the consequences to symbiont fitness when in and out of symbiosis, as well as when the symbiosis is under suboptimal or varying environments and biological conditions (e.g., host age). We find that some intracellular symbionts associated with protists tend to have greater fitness when the symbiosis is under stressful conditions. Symbionts of plants and animals did not exhibit this trend, suggesting that symbionts of multicellular hosts are more robust to perturbations. Symbiont fitness also generally increased with host age. Lastly, we show that symbionts able to proliferate in- and outside host cells exhibit greater fitness than those found exclusively inside or outside cells. The ability to grow in multiple locations may thus help symbionts thrive. We discuss these fitness patterns in light of host-driven factors, whereby hosts exert influence over symbionts to suit their own needs. Supplementary Information: The online version contains supplementary material available at 10.1007/s13199-024-00984-6.

Incomplete immunity in a natural animal-microbiota interaction selects for higher pathogen virulence.

Incomplete immunity in recovered hosts is predicted to favor more virulent pathogens upon re-infection in the population.1 The microbiota colonizing animals can generate a similarly long-lasting, partial immune response, allowing for infection but dampened disease severity.2 We tracked the evolutionary trajectories of a widespread pathogen (Pseudomonas aeruginosa), experimentally passaged through populations of nematodes immune-primed by a natural microbiota member (P. berkeleyensis). This bacterium can induce genes regulated by a mitogen-activated protein kinase (MAPK) signaling pathway effective at conferring protection against pathogen-induced death despite infection.3 Across host populations, this incomplete immunity selected for pathogens more than twice as likely to kill as those evolved in non-primed (i.e., naive) or immune-compromised (mutants with a knockout of the MAPK ortholog) control populations. Despite the higher virulence, pathogen molecular evolution in immune-primed hosts was slow and constrained. In comparison, evolving pathogens in immune-compromised hosts were characterized by substantial genomic differentiation and attenuated virulence. These findings directly attribute the incomplete host immunity induced from microbiota as a significant force shaping the virulence and evolutionary dynamics of novel infectious diseases.

Turning the tide on sex and the microbiota in aquatic animals.

Sex-based differences in animal microbiota are increasingly recognized as of biological importance. While most animal biomass is found in aquatic ecosystems and many water-dwelling species are of high economic and ecological value, biological sex is rarely included as an explanatory variable in studies of the aquatic animal microbiota. In this opinion piece, we argue for greater consideration of host sex in studying the microbiota of aquatic animals, emphasizing the many advancements that this information could provide in the life sciences, from the evolution of sex to aquaculture.

Within- and between-host dynamics of producer and non-producer pathogens.

For infections to be maintained in a population, pathogens must compete to colonize hosts and transmit between them. We use an experimental approach to investigate within-and-between host dynamics using the pathogen Pseudomonas aeruginosa and the animal host Caenorhabditis elegans. Within-host interactions can involve the production of goods that are beneficial to all pathogens in the local environment but susceptible to exploitation by non-producers. We exposed the nematode host to 'producer' and two 'non-producer' bacterial strains (specifically for siderophore production and quorum sensing), in single infections and coinfections, to investigate within-host colonization. Subsequently, we introduced infected nematodes to pathogen-naive populations to allow natural transmission between hosts. We find that producer pathogens are consistently better at colonizing hosts and transmitting between them than non-producers during coinfection and single infection. Non-producers were poor at colonizing hosts and between-host transmission, even when coinfecting with producers. Understanding pathogen dynamics across these multiple levels will ultimately help us predict and control the spread of infections, as well as contribute to explanations for the persistence of cooperative genotypes in natural populations.

Interspecific host competition and parasite virulence evolution.

Virulence, the harm to hosts caused by parasite infection, can be selected for by several ecological factors acting synergistically or antagonistically. Here, we focus on the potential for interspecific host competition to shape virulence through such a network of effects. We first summarize how host natural mortality, body mass changes, population density and community diversity affect virulence evolution. We then introduce an initial conceptual framework highlighting how these host factors, which change during host competition, may drive virulence evolution via impacts on life-history trade-offs. We argue that the multi-faceted nature of both interspecific host competition and virulence evolution still requires consideration and experimentation to disentangle contrasting mechanisms. It also necessitates a differential treatment for parasites with various transmission strategies. However, such a comprehensive approach focusing on the role of interspecific host competition is essential to understand the processes driving the evolution of virulence in a tangled bank.

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

Agricultural crops 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 will 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 fitness outcomes is diverse and span the parasitism-mutualism continuum. We found no evidence that various transmission strategies, or direct effects and indirect (plant-mediated) effects, of phytopathogens have divergent fitness outcomes for the vector. Our finding emphasizes diversity in tripartite interactions and the necessity for pathosystem-specific approaches to vector control.