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"Ford, Suzanne"
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Super sleuths
\"Violet and Dash are back for another Super adventure! This time, the siblings find themselves stuck in an after-school program. Everything about it seems so boring and normal, but they discover a new way to practice their powers to become even better Supers. Violet, Dash, and their friend Chance want to be ready for anything, especially when they investigate the biggest mystery of all: who left the strange and sinister notes in Chance's locker? A super villain could be closer than they think...\"--Page [4] of cover.
CHILDBOOK
Harnessing the Power of Defensive Microbes: Evolutionary Implications in Nature and Disease Control
[...]defensive microbes are already being applied in phage therapy and bacteriotherapy for humans, as well as to control vector-borne and agricultural diseases (Table 2). [...]coevolution between defensive microbes and parasites could provide \"real-time\" disease control, whereby evolutionary changes in parasites are met by rapid reciprocal evolution in defensive microbes. [...]microbe-mediated defence can be directly favoured when microbial fitness depends strongly on host fitness [45], such as when microbes are vertically transmitted (e.g., Wolbachia in Table 1) or when the host exercises \"partner choice\" or \"host sanctions\" and selectively cultures defensive microbes [8, 9, 11].
Journal Article
In Vivo Microbial Coevolution Favors Host Protection and Plastic Downregulation of Immunity
Abstract
Microbiota can protect their hosts from infection. The short timescales in which microbes can evolve presents the possibility that “protective microbes” can take-over from the immune system of longer-lived hosts in the coevolutionary race against pathogens. Here, we found that coevolution between a protective bacterium (Enterococcus faecalis) and a virulent pathogen (Staphylococcus aureus) within an animal population (Caenorhabditis elegans) resulted in more disease suppression than when the protective bacterium adapted to uninfected hosts. At the same time, more protective E. faecalis populations became costlier to harbor and altered the expression of 134 host genes. Many of these genes appear to be related to the mechanism of protection, reactive oxygen species production. Crucially, more protective E. faecalis populations downregulated a key immune gene, , known to be effective against S. aureus infection. These results suggest that a microbial line of defense is favored by microbial coevolution and may cause hosts to plastically divest of their own immunity.
Journal Article
Microbe-mediated host defence drives the evolution of reduced pathogen virulence
Microbes that protect their hosts from pathogens are widespread in nature and are attractive disease control agents. Given that pathogen adaptation to barriers against infection can drive changes in pathogen virulence, ‘defensive microbes’ may shape disease severity. Here we show that co-evolving a microbe with host-protective properties (
Enterococcus faecalis
) and a pathogen (
Staphylococcus aureus
) within
Caenorhabditis elegans
hosts drives the evolution of reduced pathogen virulence as a by-product of adaptation to the defensive microbe. Using both genomic and phenotypic analyses, we discover that the production of fewer iron-scavenging siderophores by the pathogen reduces the fitness of the defensive microbe and underpins the decline in pathogen virulence. These data show that defensive microbes can shape the evolution of pathogen virulence and that the mechanism of pathogen resistance can determine the direction of virulence evolution.
Some microbes protect their hosts from pathogens and likely drive pathogens’ evolution. Here, Ford
et al.
show that a host-protective microbe selects for reduced virulence of a pathogen in the model organism
Caenorhabditis elegans
.
Journal Article
MLST revisited: the gene-by-gene approach to bacterial genomics
Assessing the genetic variation of bacteria has become ever more complex as more sequencing data has become available. Here, Maiden and colleagues propose a gene-by-gene approach of analysing whole-genome data; this approach is based on their experience with multilocus sequence typing (MLST) and reflects the functional and evolutionary relationships among bacteria.
Multilocus sequence typing (MLST) was proposed in 1998 as a portable sequence-based method for identifying clonal relationships among bacteria. Today, in the whole-genome era of microbiology, the need for systematic, standardized descriptions of bacterial genotypic variation remains a priority. Here, to meet this need, we draw on the successes of MLST and 16S rRNA gene sequencing to propose a hierarchical gene-by-gene approach that reflects functional and evolutionary relationships and catalogues bacteria 'from domain to strain'. Our gene-based typing approach using online platforms such as the Bacterial Isolate Genome Sequence Database (BIGSdb) allows the scalable organization and analysis of whole-genome sequence data.
Journal Article
Rapid evolution of microbe-mediated protection against pathogens in a worm host
Microbes can defend their host against virulent infections, but direct evidence for the adaptive origin of microbe-mediated protection is lacking. Using experimental evolution of a novel, tripartite interaction, we demonstrate that mildly pathogenic bacteria (
Enterococcus faecalis
) living in worms (
Caenorhabditis elegans
) rapidly evolved to defend their animal hosts against infection by a more virulent pathogen (
Staphylococcus aureus
), crossing the parasitism–mutualism continuum. Host protection evolved in all six, independently selected populations in response to within-host bacterial interactions and without direct selection for host health. Microbe-mediated protection was also effective against a broad spectrum of pathogenic
S. aureus
isolates. Genomic analysis implied that the mechanistic basis for
E. faecalis
-mediated protection was through increased production of antimicrobial superoxide, which was confirmed by biochemical assays. Our results indicate that microbes living within a host may make the evolutionary transition to mutualism in response to pathogen attack, and that microbiome evolution warrants consideration as a driver of infection outcome.
Journal Article
Host genotype and genetic diversity shape the evolution of a novel bacterial infection
Pathogens continue to emerge from increased contact with novel host species. Whilst these hosts can represent distinct environments for pathogens, the impacts of host genetic background on how a pathogen evolves post-emergence are unclear. In a novel interaction, we experimentally evolved a pathogen (
Staphylococcus aureus
) in populations of wild nematodes (
Caenorhabditis elegans
) to test whether host genotype and genetic diversity affect pathogen evolution. After ten rounds of selection, we found that pathogen virulence evolved to vary across host genotypes, with differences in host metal ion acquisition detected as a possible driver of increased host exploitation. Diverse host populations selected for the highest levels of pathogen virulence, but infectivity was constrained, unlike in host monocultures. We hypothesise that population heterogeneity might pool together individuals that contribute disproportionately to the spread of infection or to enhanced virulence. The genomes of evolved populations were sequenced, and it was revealed that pathogens selected in distantly-related host genotypes diverged more than those in closely-related host genotypes.
S. aureus
nevertheless maintained a broad host range. Our study provides unique empirical insight into the evolutionary dynamics that could occur in other novel infections of wildlife and humans.
Journal Article
Immune-mediated competition benefits protective microbes over pathogens in a novel host species
Microbes that protect against infection inhabit hosts across the tree of life. It is unclear whether and how the host immune system may affect the formation of new protective symbioses. We investigated the transcriptomic response of Caenorhabditis elegans following novel interactions with a protective microbe (Enterococcus faecalis) able to defend against infection by pathogenic Staphylococcus aureus. We have previously shown that E. faecalis can directly limit pathogen growth within hosts. In this study, we show that colonisation by protective E. faecalis caused the differential expression of 1,557 genes in pathogen infected hosts, including the upregulation of immune genes such as lysozymes and C-type lectins. The most significantly upregulated host lysozyme gene, lys-7, impacted the competitive abilities of E. faecalis and S. aureus when knocked out. E. faecalis has an increased ability to resist lysozyme activity compared to S. aureus, suggesting that the protective microbe could gain a competitive advantage from this host response. Our finding that protective microbes can benefit from immune-mediated competition after introduction opens up new possibilities for biocontrol design and our understanding of symbiosis evolution. Crosstalk between the host immune response and microbe-mediated protection should favour the continued investment in host immunity and avoid the potentially risky evolution of host dependence.
Journal Article
The impact of artificial selection for Wolbachia-mediated dengue virus blocking on phage WO
Wolbachia is currently at the forefront of global efforts to control arbovirus transmission from the vector Aedes aegypti . The use of Wolbachia relies on two phenotypes—cytoplasmic incompatibility (CI), conferred by cifA and cifB genes in prophage WO, and Wolbachia -mediated pathogen blocking (WMPB). These traits allow for local, self-sustaining reductions in transmission of dengue (DENV) following release of Wolbachia -infected A . aegypti . Here, aided by previous artificial selection experiment that generated Low and High pathogen blocking lines, we examined the potential link between WMPB and phage WO. We found no evidence that Wolbachia or phage WO relative densities predict DENV blocking strength across selected lines. However, selection resulted in reduced phage WO relative density for the Low WMPB line. The Low blocking line was previously shown to have reduced fitness as a result of selection. Through subsequent genomic analyses, we demonstrate that SNP variation underpinning selection for low blocking led to elevated frequency of potential deleterious SNPs on chromosome 1. The key region on chromosome 1 contains genes relating to cell cycle regulation, oxidative stress, transcriptional pausing, among others, that may have cascading effects on Wolbachia intracellular environment. We hypothesize that reduction in phage WO may be driven by changes in the loci directly under selection for blocking, or by the accumulation of predicted deleterious alleles in linkage disequilibrium with blocking loci resulting from hitchhiking. For the Low line with fewer phage WO, we also detected reduced expression of cifA and cifB CI genes, with patterns of expression varying between somatic and reproductive tissues. In conclusion, we propose that artificial selection for WMPB trait had corresponding impacts on phage WO densities, and also the transcription of CI-causing genes. Future studies may include a more detailed analysis of the regions the A . aegypti chromosome 1’s ability to affect WMPB and other Wolbachia -associated intrinsic factors such as phage WO.
Journal Article
Patient and carer perceptions of video, telephone and in-person clinics for Phenylketonuria (PKU)
Background
In phenylketonuria (PKU), attending multidisciplinary clinic reviews is an important aspect of life-long care. Since the COVID-19 pandemic, video and telephone clinics are used as alternative methods for people with PKU to have contact with their care team. There is limited research concerning patient preference, experience and perceptions of alternative types of clinic review. Individuals from the UK with PKU and their caregivers were invited to complete an online questionnaire, hosted on the National Society for PKU (NSPKU) website and social media platform.
Results
Data was available from 203 respondents. Forty one per cent of respondents (
n
= 49/119) preferred in-person clinics; 41% (
n
= 49) a hybrid of in-person, video and telephone clinics; 9% (
n
= 11) video clinics only, 6% (
n
= 7) telephone only and 3% (
n =
3) were unsure. The main respondent obstacles to in-person clinics were costs, travel and time, but this was balanced by the benefits of a physical examination and better patient engagement/motivation. Twenty one per cent (
n
= 36/169) of respondents were uncomfortable with the number of healthcare professionals (HCPs) in a clinic room. Patients were less likely to consult with a doctor on video (64%,
n
= 91/143) or phone (50%,
n =
59/119) reviews compared to in-person (80%,
n
= 146/183). Issues with video and telephone reviews included the shorter time length of review, distractions, technical issues and poor patient engagement.
Conclusions
Online video and telephone clinic platforms were effective in overcoming the challenging circumstances in management, monitoring and treatment of patients with PKU during the COVID-19 pandemic. However, in-person clinics remain the preferred respondent option. It is important that HCPs are flexible, enabling people with PKU a choice of clinic options according to their individual clinical need and circumstances.
Journal Article