Research Focus: From sleeping sickness in domestic dogs to infectious, neoplastic lung disease in sheep

A collection of publication highlights from the Edinburgh Infectious Diseases network over the past month.

Africanis dog in Botswana

Domestic dogs as reservoirs for African trypanosomiasis in Mambwe district, eastern Zambia

Researchers from the department of Infection Medicine within the College of Medicine and Veterinary Medicine have been looking into the control of African trypanosomiasis (sleeping sickness) which faces a lot of challenges due to the involvement of wild and domestic animal reservoirs. Researchers focussed on the reservoir role of such dogs in maintaining and transmitting diverse species of trypanosomes that are infective to humans and livestock in Zambia's Mambwe district.

 

This study demonstrates that the Trypanosoma reservoir community in Zambia is wider than was thought and includes domesticated dogs. As dogs are active carriers of human and livestock-infective trypanosomes, they pose a risk of transmitting AT in endemic villages of Mambwe.

 

Citation: Lisulo M, Namangala B, Mweempwa C, Banda M, Chambaro H, Moonga L, Kyoko H, Chihiro S, Picozzi K, Maciver SK, MacLeod ET. Sci Rep. 2024 Sep 10;14(1):21062. doi: 10.1038/s41598-024-69834-1. 

Can biosampling really be "non-invasive"? An examination of the socially invasive nature of physically non-invasive biosampling in urban and rural Malawi

Researchers from the Centre for Biomedicine, Self and Society within the Usher Institute have been researching whether biosampling can ever be "non-invasive". 

 

Glucocorticoids are understood to represent useful biomarkers of stress and can be measured in saliva, hair, and breastmilk. Collection of these biomarkers is used in biobank and cohort studies and are said to be "non-invasive". Researchers have conducted a qualitative study using focus groups to determine the feasbility and acceptability of collecting "non-invasive" biological samples in Malawi.

 

Participants described biomaterials intended for "non-invasive" collection as sometimes highly sensitive, with sampling procedures raising community concerns. The study concluded that when researchers engage with communities about biosampling, they must ensure they are not furthering therapeutic misconceptions and actively seek to dispel these.

 

Citation: Ndambo MK, Bunn C, Pickersgill M, Stewart RC, Crampin AC, Nyasulu M, Kanyenda B, Mnthali W, Umar E, Reynolds RM, Manda-Taylor L. Glob Bioeth. 2024 Sep 9;35(1):2398303. doi: 10.1080/11287462.2024.2398303. 

In vitro and ex vivo models of microbial keratitis: Present and future

Researchers from the Centre for Inflammation Research are providing vital research into Microbial keratitis (MK) which is an infection of the corena leading to significant morbidity, being the fifth leading cause of blindness worldwide. There is an urgent need for a better understandding of this infection in order to improve patient outcomes.

 

As a result, researchers present current in vitro and ex vivo MK model systems and examine their varied design, outputs, reporting standards, and strengths and limitations. There remains a dependence on in vivo models to study MK.

 

Looking to the future, researchers draw from the broader field of corneal disease modelling, which utilises, for example, three-dimensional co-culture models and dynamic environments observed in bioreactors and organ-on-a-chip scenarios. 

 

Citation: Cheng KKW, Fingerhut L, Duncan S, Prajna NV, Rossi AG, Mills B. Prog Retin Eye Res. 2024 Sep;102:101287. doi: 10.1016/j.preteyeres.2024.101287. Epub 2024 Jul 14.

Peptide-mimetic treatment of Pseudomonas aeruginosa in a mouse model of respiratory infection

The rise of drug reistance has become a global problem. In particular, Pseudomonas aeruginosa is a multi-drug resistance pathogen and remains a serious issue with limited solutions due to its complex resistance mechanisms.

 

Researchers from the Institute for Immunology and Infection Research have found that a potential new therapeutic, the peptide-mimetic TM5, is effective at killing P. aeruginosa and displays sufficiently low toxicity in mammalian cells to allow for use in treatment of infections.

 

TM5 kills P. aeruginosa more rapidly than traditional antibiotics, within 30-60 min in vitro, and is effective against a range of clinical isolates, including extensively drug resistant strains. 

 

Researchers conclude that TM5 shows promise as an alternative therapy for P. aeruginosa respiratory infections.

 

Citation: Moule MG, Benjamin AB, Burger ML, Herlan C, Lebedev M, Lin JS, Koster KJ, Wavare N, Adams LG, Bräse S, Munoz-Medina R, Cannon CL, Barron AE, Cirillo JD. Commun Biol. 2024 Aug 22;7(1):1033. doi: 10.1038/s42003-024-06725-1. Erratum in: Commun Biol. 2024 Sep 13;7(1):1137. doi: 10.1038/s42003-024-06863-6.

Infectious bronchitis virus vaccination, but not the presence of XCR1, is correlated with large differences in chicken caecal microbiota

The chicken immune system and microbiota play vital roles in maintaining gut homeostasis and protecting against pathogens. In mammals XCR1+ conventional dendritic cells play a major role in gut homeostasis.

 

Researchers from The Roslin Institute and Scotland's Rural College have hypothesized that these cells play similar roles in sustaining gut homeostasis in chickens and chickens lacking these cells were likely to contain dysbiotic caecal microbiota (the substitution of normal gut flora to dysfunctional gut flora that can promote disease states). 

 

Researchers found that a lack of XCR1 was not correlated with significant changes in the chicken microbiotas. However, IBV vaccination was found to correlate with significant differences in the richness and beta diversity of the microbiota.

 

Citation: Glendinning L, Wu Z, Vervelde L, Watson M, Balic A. Microb Genom. 2024 Sep;10(9). doi: 10.1099/mgen.0.001289.

Mitochondrial background can explain variable costs of immune deployment

Researchers from the Institute of Ecology and Evolution have been looking at immune responses to infections. These responses are vital for organismal health and surivival. 

 

Researchers employed Drosophila melanogaster cybrid lines and explosed female flies carrying one of nine distinct mitotypes to either a benign, heat-killed bacterial pathogen or to a sterile control and measured lifespan, fecundity, and locomotor activity.

 

Their results suggests that costs of immunity are highly variable depending on the mitochondrial genome, adding to a growing body of work highlighting the important role of mitochondrial variation in host-pathogen interactions.

 

Citation: Kutzer MAM, Cornish B, Jamieson M, Zawistowska O, Monteith KM, Vale PF. J Evol Biol. 2024 Aug 27;37(9):1125-1133. doi: 10.1093/jeb/voae082.

Differential roles for the oxygen sensing enzymes PHD1 and PHD3 in the regulation of neutrophil metabolism and function

Neutrophils are essential in the early innate immune response to pathogens. Harnessing their antimicrobial powers, without driving excessive and damaging inflammatory responses, represents an attractive therapeutic possibility.
 
Researchers from the Institute for Regeneration and Repair used a combination of in vivo and ex vivo models, utilising neutrophil and myeloid specific PHD1 or PHD3 deficient mouse lines to investigate the roles of oxygen sensing prolyl hydroxylase enzymes in the regulation of neutrophilic inflammation and immunity.
 
Researchers found that PHD1 deficiency drives alterations in neutrophil metabolism and recruitment, in an oxygen dependent fashion.
 
Citation: Watts E, Willison J, Arienti S, Sadiku P, Coelho P, Sanchez-Garcia M, Zhang A, Murphy F, Dickinson R, Mirchandani A, Morrison T, Lewis A, Vermaelen W, Ghesquiere B, Carmeliet P, Mazzone M, Maxwell P, Pugh C, Dockrell D, Whyte M, Walmsley S. Wellcome Open Res. 2024 Sep 2;8:569. doi: 10.12688/wellcomeopenres.19915.2.

Tracking Ovine Pulmonary Adenocarcinoma Development Using an Experimental Jaagsiekte Sheep Retrovirus Infection Model

Researchers from the Moredun Research Institute, the Royal (Dick) School of Veterinary Studies, The Roslin Institute, Edinburgh Imaging Facility and the Centre for Clinical Brain Studies have conducted a major project on Ovine Pulmonary Adenocarcinoma (OPA). OPA is an infectious, neoplastic lung disease of sheep that causes large animal welfare and economic issues throughout the world.

 

Researchers report the development of an experimentally induced OPA model intended to monitor and track events after Jaagsiekte sheep retrovirus (JSRV) infection.

 

Researchers believe that the range of OPA lesion types induced by this model replicates aspects of naturally occurring disease and will improve OPA research by providing novel insights into JSRV infectivity and OPA disease progression.

 

Citation: Cousens C, Meehan J, Collie D, Wright S, Chang Z, Todd H, Moore J, Grant L, Daniel CR, Tennant P, Ritchie A, Nixon J, Proudfoot C, Guido S, Brown H, Gray CD, MacGillivray TJ, Clutton RE, Greenhalgh SN, Gregson R, Griffiths DJ, Spivey J, Storer N, Eckert CE, Gray M. Genes (Basel). 2024 Aug 2;15(8):1019. doi: 10.3390/genes15081019.

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