Biology subjects

Gage, H.

Publications and source records attributed to Gage, H..

4 recordsLinked to original sources

bioRxiv2025

Reduced efficacy of an anti-toxin vaccine from senescence-driven attenuation of toxin virulence

It remains unclear why vaccines targeting prominent microbial virulence factors often fail in clinical trials. Because microbial virulence depends on interaction with the host immune system, we investigated how changes in host immune function alter vaccine efficacy. Using a vaccine against Staphylococcus aureus alpha toxin (Hla), which targets host metalloprotease ADAM10 on myeloid cells, we show that Hla virulence is reduced in aged mice due to diminished ADAM10 activity and impaired myeloid cell function. Depletion of myeloid cells with cyclophosphamide in young mice similarly reduced toxin virulence. Immunization against Hla conferred strong protection against Staphylococcus aureus infection in young but not aged mice. These findings indicate that pathogenic functions of microbial factors characterized in immunocompetent young animals may not predict virulence or vaccine efficacy in immunocompromised hosts. These findings underscore the need to account for host immune status in the development and evaluation of vaccines targeting microbial virulence factors.

microbiology↗

bioRxiv2023

Spores of the fungal pathogen Cryptococcus exhibit cell type-specific carbon source utilization during germination

Spores are critical morphotypes required for long-term survival of most fungi. Under the right environmental conditions, spores can escape dormancy and differentiate into vegetatively growing cells through the process of germination. For fatal human fungal pathogens like Cryptococcus, germination is the key differentiation process required for spores to initiate vegetative growth and ultimately cause disease; however, relatively little is known about the molecular mechanisms that control germination. To this end, we performed an extensive characterization of Cryptococcus spore germination through the morphological assessment of germinating spores, the inhibition of key eukaryotic processes, and the detailed quantification of fungal spore germination kinetics under numerous nutrient conditions. We identified temporal associations between molecular and morphological events and determined that carbon metabolism pathways (both glycolysis and oxidative phosphorylation) were required from the beginning of germination. We further determined that carbon sources are primarily used as fuel rather than as simply triggers of germination commitment, and identified spore-specific carbon source utilization that is absent in yeast. Finally, we discovered the first spore-specific enzyme, Nth2, a trehalase that is required for germination when trehalose is the primary available carbon source. Together this work provides an extensive characterization of Cryptococcus spore germination and suggests that germination is more than simply a modified cell cycle but is rather a highly adapted differentiation process.

microbiology↗

bioRxiv2023

Invasive Californian death caps develop mushrooms unisexually and bisexually

Canonical sexual reproduction among basidiomycete fungi involves the fusion of two haploid individuals of different sexes, resulting in a heterokaryotic mycelial body made up of genetically different nuclei1. Using population genomics data, we discovered mushrooms of the deadly invasive Amanita phalloides are also homokaryotic, evidence of sexual reproduction by single individuals. In California, genotypes of homokaryotic mushrooms are also found in heterokaryotic mushrooms, implying nuclei of homokaryotic mycelia also promote outcrossing. We discovered death cap mating is controlled by a single mating-type locus (A. phalloides is bipolar), but the development of homokaryotic mushrooms appears to bypass mating-type gene control. Ultimately, sporulation is enabled by nuclei able to reproduce alone as well as with others, and nuclei competent for both unisexuality and bisexuality have persisted in invaded habitats for at least 17 but potentially as long as 30 years. The diverse reproductive strategies of invasive death caps are likely facilitating its rapid spread, revealing a profound similarity between plant, animal and fungal invasions2,3.

microbiology↗

bioRxiv2020

Physiotherapist and Podiatrist Independent Prescribing in the United Kingdom: A quasi experimental study

BackgroundIncreasing numbers of nurses, pharmacists and allied health professionals across the world have prescribing rights: over 90,000 of the eligible United Kingdom workforce are qualified as non-doctor prescribers. In order to inform future developments, it is important to understand the benefits and impact of prescribing by allied health professionals including physiotherapists and podiatrists. Aim: to compare outcomes of Physiotherapist and Podiatrist Independent Prescriber (PP-IP) patients with those of Physiotherapist and Podiatrist non-prescribers (PP-NPs). Outcome measures included patient satisfaction, ease of access to services, quality of life and cost implications. Design: a quasi-experimental, post-test control group design Methods: Using mixed methods outcomes were compared between 7 sites where care was provided from a PP-IP (3 podiatrist and 4 physiotherapist IPs) and 7 sites from a PP-NP (3 podiatrist and 4 physiotherapist NPs). Patients were followed up for 2 months (2015-2016). Results: 489 patients were recruited: n=243 IP sites, and n=246 NP sites. Independent prescribing was found to be highly acceptable, and equivalent in terms of quality of life (p>0.05) and patient satisfaction (p[≤]0.05) compared to care provided by NPs. PP-IP care delivery was found to be more resource intensive than NP-PP, with longer consultation duration for IPs (around 6.5 mins), and a higher proportion of physiotherapy patients discussed with medical colleagues (around 9.5 minutes). ConclusionThis study provides new knowledge that PP-IPs provide high levels of care. PP-IP care delivery was found to be more resource intensive. Further research is required to explore cost effectiveness. A more focussed exploration within each profession using targeted outcome measures would enable a more robust comparison, inform future developments around the world and help ensure non-doctor prescribing is recognised as an effective way to alleviate shortfalls in the global workforce.

scientific communication and education↗