Research Focus: From parasites in sheep to new approaches for preventing STIs

February 2025: A collection of publication highlights from Edinburgh Infectious Diseases over the past month.

Soay sheep
Soay sheep

T-helper cell phenotypes are repeatable, positively correlated, and associated with helminth infection in wild Soay sheep

Researchers from the Moredun Research Institute and Institute of Ecology and Evolution have been looking into the causes of helminth infections in wild Soay sheep. Helminths are parastic worms.

 

T-helper (Th) cells co-ordinate immune responses to ensure that infections with diverse parasites are controlled effectively. Although laboratory models have reported that Th1 and Th2 can be antagonistic, this has been challenged by studies of natural infections. 

 

Between 2019 and 2022 researchers completed 759 captures of 538 wild Soay sheep and monitored body weight, parasite egg counts, Th phenotypes, cytokines, and GIN-specific antibodies. 

 

They found that while different Th cell counts, cytokines and antibody isotypes were generally positively correlated with each other, no strong positive associations were observed between these measurements. 

 

Their results provide insights into how different aspects of immune function interact to produce effective responses to complex infections but suggest longer-term data collection is required to address the causes of these interactions.

 

Citation: Corripio-Miyar Y, Hayward AD, Lemon H, Bal X, Cunnea C, Kenyon F, Pilkington JG, Pemberton JM, Nussey DH, McNeilly TN. Discov Immunol. 2025 Feb 8;4(1):kyae017. doi: 10.1093/discim/kyae017. PMID: 39963298; PMCID: PMC11832277.

The potential virulence of Listeria monocytogenes strains isolated from fresh produce processing facilities as determined by an invertebrate Galleria mellonella model

Researchers from Edinburgh Napier University have been investgiating the virulence of nine Listeria monocytogenes strains from fresh produce-processing facilities using the Galleria mellonella (wax moth larvae) infection model. 

 

Researchers observed significant differences in mortality rates among the Listeria strains, with some causing significantly higher larval deaths than others. These differences in virulence did not correlate with the predicted virulence, nor the strains' growth rates in laboratory media.

 

The study suggests that L. monocytogenes strains from fresh produce-processing facilities exhibit varying levels of pathogenicity, posing potential risks to human health.

 

Citation: Bah U, de Llanos Frutos R, Donnellan S, Smith A, Flockhart A, Singleton I, Wheelhouse N. PLoS One. 2024 Dec 12;19(12):e0311839. doi: 10.1371/journal.pone.0311839. PMID: 39666623; PMCID: PMC11637379.

Identification of novel PfEMP1 variants containing domain cassettes 11, 15 and 8 that mediate the Plasmodium falciparum virulence-associated rosetting phenotype

A recent paper in PLoS Pathogens led by two Hosts Parasites and Global Health PhD students Dr Flo McLean and Brian Omondi in the School of Biological Sciences reveals new ways that malaria parasites bind to red blood cells. 

 

The study focussed on the parasite adhesion property of rosetting, whereby Plasmodium falciparum-infected red cells stick to uninfected human red cells to form clumps that hinder blood flow in microvessels and contribute to the pathology of life-threatening malaria.  

 

The new work harnesses a treasure-trove of parasite genome sequence data and a set of culture-adapted Kenyan parasite lines to identify parasite adhesion molecules expressed on the surface of infected red cells that are responsible for rosette formation.

 

The findings are important in understanding the host-parasite interactions underlying the unique virulence of P. falciparum and informing the potential for adhesion-blocking therapies to treat severe malaria.  

 

Citation: McLean FE, Omondi BR, Diallo N, Otoboh S, Kifude C, Abdi AI, Lim R, Otto TD, Ghumra A, & Rowe JA. (2025). PLoS Pathogens, 21(1), e1012434. https://doi.org/10.1371/journal.ppat.1012434  

Structural basis of promiscuous inhibition of Listeria virulence activator PrfA by oligopeptides

A new study by the Vazquez-Boland group (Centre for Inflammation Research) in collaboration with colleagues at the University of Umea in Sweden, elucidates the strucutural mechanism behind the promiscuous (sequence-indepedent) inhibition of the Listeria central virulence regulator PrfA by environmental oligopeptides. 

 

The mechanism is critical for ensuring that the fitness-costly virulence programme of the foodborne pathogen Listeria monocytogenes is not expressed outside the host, when the bacteria are living saprophytically in the environment. 

 

The structural insights gained though this study can be exploited to develop anti-virulence drugs to prevent and treat foodborne listeriosis.  

 

Citation: Tobias Hainzl, Mariela Scortti, Cecilia Lindgren, Christin Grundström, Emilia Krypotou, José A. Vázquez-Boland, A. Elisabeth Sauer-Eriksson, Cell Reports, Volume 44, Issue 2, 2025, 115290, ISSN 2211-1247. https://doi.org/10.1016/j.celrep.2025.115290.

Controlled human infection model of Neisseria lactamica in late pregnancy investigating mother-to-infant transmission in the UK: a single-arm pilot trial

Researchers from the Bogaert lab in the Centre for Inflammation Research have been looking into the infant respiratory microbiome, which is largely derived from the mother, and manipulating this maternal respiratory flora in order to influence the infant microbiome. 

 

Neisseria lactamica is a harmless bacteria that correlates inversely with Neisseria meningitidis carriage and disease. In this single-arm trial, 21 healthy pregnant female participants aged 18 years or older were inoculated at 36-38 weeks' with N. lactamica.  15 mothers became colonised with the bacteria, but no vertical transimission to their infants was observed.

 

As the world's first perinatal Controlled Human Infection Model (CHIM), this trial demonstrates that this model in pregnancy is feasible, and that N. lactamica can safely and efficiently colonise pregnant individuals. 

 

Citation: Theodosiou AA, Bogaert D, Cleary DW, Dale AP, Gbesemete DF, Guy JM, Laver JR, Raud L, Jones CE, Read RC. Lancet Microbe. 2025 Feb 19:100986. doi: 10.1016/j.lanmic.2024.100986. Epub ahead of print. PMID: 39986292.

Chromosomal genome assembly resolves drug resistance loci in the parasitic nematode Teladorsagia circumcincta

The parasitic nematode Teladorsagia circumcincta (T. circumcincta) is one of the most important pathogens of sheep and goats in temperate climates worldwide and can rapidly evolve resistance to drugs.
 
Researchers from Moredun Research Institute and the Royal (Dick) School of Veterinary Studies have generated a highly contiguous genome assembly for the UK T. circumcincta isolate to understand the genetics of drug resistance.
 
Their genome-wide analyses of drug resistance, combining evidence from three distinct experiments, identified selection around known candidate genes as well as novel regions.
 
These insights into contemporary and historic genetic selection further emphasise the importance of contiguous genome assemblies in interpreting genome-wide genetic variation associated with drug resistance
 
Citation: McIntyre J, Morrison A, Maitland K, Berger D, Price DRG, Dougan S, Grigoriadis D, Tracey A, Holroyd N, Bull K, Rose Vineer H, Glover MJ, Morgan ER, Nisbet AJ, McNeilly TN, Bartley Y, Sargison N, Bartley D, Berriman M, Cotton JA, Devaney E, Laing R, Doyle SR. PLoS Pathog. 2025 Feb 6;21(2):e1012820. doi: 10.1371/journal.ppat.1012820. PMID: 39913358; PMCID: PMC11801625.

DoxyPEP: thinking towards implementation

Researchers from the Usher Institute have been looking into DoxyPEP, which is a promising new approach to preventing bacterial sexually transmitted infections (STIs), and involves taking the antibiotic doxycycline after potential exposure. 

 

As STI rates rise, interest in DoxyPEP is growing, but its implementation raises important questions about access, stigma, and antimicrobial resistance. 

 

This paper brings together insights from an expert roundtable at the University of Edinburgh, where clinicians, researchers, activists, and community members discussed how to ensure DoxyPEP is introduced in a way that is equitable and effective. Drawing lessons from the rollout of HIV PrEP, the discussion emphasized the need for community-driven models, balanced conversations around antibiotic use, and a holistic approach that sees sexual health as more than just infection prevention. The recording of the session can also be found in the HIV Matters podcast

 

Citation: Jaime Garcia-Iglesias, Chase Ledin, John Gilmore, Manik Kohli, Eddy Smith, Benjamin Weil, Laia Ventura Garcia,The Lancet Infectious Diseases, 2025, ISSN 1473-3099, https://doi.org/10.1016/S1473-3099(25)00077-5.