ORCID Profile
0000-0003-4988-409X
Current Organisations
Monash University
,
University of Oxford
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Wiley
Date: 10-2019
DOI: 10.1002/ECE3.5704
Publisher: Wiley
Date: 14-02-2022
DOI: 10.1111/IMB.12764
Abstract: One approach to control dengue virus transmission is the symbiont Wolbachia , which limits viral infection in mosquitoes. Despite plans for its widespread use in Aedes aegypti , Wolbachia 's mode of action remains poorly understood. Many studies suggest that the mechanism is likely multifaceted, involving aspects of immunity, cellular stress and nutritional competition. A previous study from our group used artificial selection to identify a new mosquito candidate gene related to viral blocking alpha‐mannosidase‐2a ( alpha‐Mann‐2a ) with a predicted role in protein glycosylation. Protein glycosylation pathways tend to be involved in complex host–viral interactions however, the function of alpha‐mannosidases has not been described in mosquito–virus interactions. We examined alpha‐Mann‐2a expression in response to virus and Wolbachia infections and whether reduced gene expression, caused by RNA interference, affected viral loads. We show that dengue virus (DENV) infection affects the expression of alpha‐Mann‐2a in a tissue‐ and time‐dependent manner, whereas Wolbachia infection had no effect. In the midgut, DENV prevalence increased following knockdown of alpha‐Mann‐2a expression in Wolbachia ‐free mosquitoes, suggesting that alpha‐Mann‐2a interferes with infection. Expression knockdown had the same effect on the togavirus chikungunya virus, indicating that alpha‐Mann‐2a may have broad antivirus effects in the midgut. Interestingly, we were unable to knockdown the expression in Wolbachia ‐infected mosquitoes. We also provide evidence that alpha‐Mann‐2a may affect the transcriptional level of another gene predicted to be involved in viral blocking and cell adhesion cadherin87a . These data support the hypothesis that glycosylation and adhesion pathways may broadly be involved in viral infection in Ae. aegypti .
Publisher: Springer Science and Business Media LLC
Date: 15-11-2016
DOI: 10.1038/NCOMMS13430
Abstract: 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.
Publisher: Public Library of Science (PLoS)
Date: 08-04-2016
Publisher: Springer Science and Business Media LLC
Date: 26-08-2019
Publisher: Springer Science and Business Media LLC
Date: 18-02-2021
DOI: 10.1038/S41396-021-00911-3
Abstract: 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 ersity 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 in iduals 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 erged 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.
Publisher: Wiley
Date: 05-12-2016
DOI: 10.1111/MEC.13906
Publisher: Cold Spring Harbor Laboratory
Date: 25-11-2019
DOI: 10.1101/847087
Abstract: Wolbachia is an intracellular bacterium that blocks virus replication in insects and has been introduced into the mosquito, Aedes aegypti for the biocontrol of arboviruses including dengue, Zika and chikungunya. Despite ongoing research, the mechanism of Wolbachia -mediated virus blocking remains unclear. We recently used experimental evolution to reveal that Wolbachia -mediated dengue blocking could be selected upon in the A. aegypti host and showed evidence that strong levels of blocking could be maintained by natural selection. In this study, we investigate the genetic variation associated with blocking and use these analyses to generate testable hypotheses surrounding the mechanism of Wolbachia -mediated dengue blocking. From our results, we hypothesise that Wolbachia may block virus replication by increasing the regeneration rate of mosquito cells via the Notch signalling pathway. We also propose that Wolbachia modulates the host’s transcriptional pausing pathway either to prime the host’s anti-viral response or to directly inhibit viral replication.
Publisher: Springer Science and Business Media LLC
Date: 15-03-2016
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Suzanne A Ford.