January 2025: A collection of publication highlights from Edinburgh Infectious Diseases over the past month. Chinese rufous horseshoe bat Alternative splicing expands the antiviral IFITM repertoire in Chinese rufous horseshoe bats PhD student Nelly Mak, from the Richard Sloan lab in the Centre for Inflammation Research has published a paper in PLoS Pathogens showing how splice variation in antiviral IFITM genes in bats broadens their innate immune responses. Bats are a recurring source of viral spillovers and pandemics and it is thought their unique antiviral and anti-inflammatory immunology might be behind this phenomenon. In this study, researchers examined antiviral IFITM proteins in the Chinese horseshoe bat, the origin of the SARS coronavirus that emerged in 2002 and a known carrier of SARS-CoV-2 like viruses. They showed that splice variation allows IFITM proteins in bats to make multiple forms of IFITM proteins that can can block off different cell entry routes to coronaviruses and influenza A virus. This finding is important in understanding how viruses are propagated in horseshoe bats and spillover from them into the human population. Citation: Mak NSC, Liu J, Zhang D, Taylor J, Li X, Rahman K, Chen F, Datta SAK, Lai KK, Shi Z, Temperton N, Irving AT, Compton AA, Sloan RD. PLoS Pathog. 2024 Dec 26. Read the full article here A naturally occurring mitochondrial genome variant confers broad protection from infection in Drosophila Responses to infection vary among individuals even when exposed to the same pathogen. Much of this variation is due to the genes directly involved in immunity, but mitochondria are emerging as one of the factors modulating immune responses. Mitochondria are cellular organelles with their own genome (mtDNA) involved in many important processes, including producing ATP, the energy currency of the cells. mtDNA mutations leading to mitochondrial dysfunction are often considered harmful upon exposure to pathogens. Researchers from the School of Biological Sciences used a fruit fly model where unique mtDNA variants are placed in a controlled nuclear genomic background to find out how mtDNA shapes infection outcomes upon bacterial, viral and parasitoid infections. They found that mtDNA variation alters the efficiency of immune response and describe a mtDNA variant that confers protection against variety of pathogens by inducing higher numbers of immune cells prior to and during infection. Citation: Salminen TS, Vesala L, Basikhina Y, Kutzer M, Tuomela T, Lucas R, Monteith K, Prakash A, Tietz T, Vale PF. PLoS Genet. 2024 Nov 11 Read the full article here Microbiotoxicity: A call to arms for cross-sector protection of the human microbiome Recent studies add to the growing body of evidence showing that antibiotic use can be harmful to the human microbiome. Researchers from the Centre for Inflammation Research and colleagues have coined the term 'microbiotoxicity' to describe unintended harms of antibiotic therapy to the microbiome, proposing a framework for prescribers to weigh these bystander effects against intended therapeutic benefits. It is becoming increasingly clear that microbiotoxicity extends far beyond antibiotics, encompassing non-antibiotic pharmaceuticals, dietary additives, and biocide-containing consumer products, thus researchers argue that all products with antimicrobial properties may cause unintended microbiotoxicity. Citation: Theodosiou AA, Fady PE, Bennett N, Read RC, Bogaert D, Jones CE. J Infect. 2025 Jan 7. Read the full article here Antimicrobial resistance profiles and molecular epidemiology of Klebsiella pneumoniae isolates from Scottish bovine mastitis cases Researchers from Scotland's Rural College, Royal (Dick) School of Veterinary Studies and The Roslin Institute have been studying Klebsiella pneumoniae which are opportunistic pathogens with the ability to cause mastitis in dairy cattle. K. pneumoniae mastitis often has a poor cure rate and can lead to the development of chronic infection, which has an impact on both health and production. Researchers identified K. pneumoniae isolates associated with mastitis in dairy cattle. Forty-two isolates identified as K. pneumoniae were subject to whole-genome sequencing. Across the dataset, there were notable levels of observable AMR against a variety of antibiotics. Citation: Pollock J, Foster G, Henderson K, Bell J, Hutchings MR, Paterson GK. Epidemiol Infect. 2025 Jan 17. Read the full article here Human ACE2 transgenic pigs are susceptible to SARS-CoV-2 and develop COVID-19-like disease Researchers from the University of Edinburgh have been looking into animal models that can accurately reflect COVID-19 as this is vital for understanding mechanisms of the disease and development of vaccines and therapeutics. Pigs are valuable models for human disease because of their genetic, anatomical, physiological and immunological similarties to humans. However, pigs are not susceptible to SARS-CoV-2 infection which limits their utility as a model in this case. Therefore, researchers have developed transgenic pigs expressing human ACE2 (an enzyme) that are susceptible to SARS-CoV-2 infection Researchers found that clinical signs consistent with COVID-19, including fever, coughing and respiratory distress were observed and therefore this study establishes human ACE2 transgenic pigs as a large animal model that accurately reflects many aspects of COVID-19 disease. Citation: Chau LF, Lillico S, Opriessnig T, Blake R, Tardy L, Lee CH, Maxwell S, Warren C, Thornton E, Mclaughlin CL, McLachlan G, Tait-Burkard C, Fletcher S, Anderson S, Brown S, Gibbard L, Tzelos T, MacMillan-Christensen D, Baillie JK, Dorward DA, Griffiths DJ, Grey F. Nat Commun. 2025 Jan 17 Read the full article here The burden of hepatitis E virus infection among Ghanaian pregnant women Hepatitis E virus (HEV) infection poses a significant burden on pregnant women, with associated negative outcomes. Researchers from the School of Biological Sciences and Edinburgh Medical School are looking to understand its impact on maternal and fetal health in Ghana. Researchers conducted a cross-sectional survey in the antenatal clinics of 10 district hospitals in five regions of Ghana. The study involved 1,000 pregnant women attending antenatal care. Assays were employed to determine HEV seroprevalence (the level of a pathogen in a population) and prevalence. HEV-Immunoglobulin G (IgG) seroprevalence of 8.3% was recorded among the pregnant women with 1% HEV-antigen prevalence. 19.8% of the pregnant women reported poor pregnancy outcomes in previous pregnancies. Age, educational attainment, and region were significant predictors of HEV IgG seropositivity. As a result, researchers suggest pregnancy care must be significantly improved to reduce maternal and foetal morbidity and mortality. Citation: Bagulo H, Majekodunmi AO, Welburn SC, Bimi L. Front Public Health. 2025 Jan 7. Read the full article here Asymptomatic infection and antibody prevalence to co-occurring avian influenza viruses vary substantially between sympatric seabird species following H5N1 outbreaks Researchers from the Institute of Ecology and Evolution, Royal (Dick) School of Veterinary Studies and the Roslin Institute are studying high pathogenicity avian influenza virus (AIV) which has led to substantial global mortality across a range of host species. Co-occurring species showed marked differences in mortality, generating an urgent need for better epidemiological understanding within affected populations. Researchers tested for antibodies, indicative of previous exposure and recovery, and for active viral infection in apparently healthy individuals (n = 350) across five co-occurring seabird species on the Isle of May, Scotland, during 2023. Researchers found low levels of active, but asymptomatic, AIV infection in individuals (1.6-4.5%). Our results emphasise the importance of testing healthy individuals to understand the prevalence of co-circulating AIV subtypes in wild populations. Citation: Greco F, Ravenswater HM, Ruiz-Raya F, D'Avino C, Newell MA, Hewitt J, Taylor E, Benninghaus E, Daunt F, Goodman G, Steel D, Park J, Philip E, Thomas SS, Slomka MJ, Falchieri M, Reid SM, James J, Banyard AC, Burthe SJ, Cunningham EJA. Sci Rep. 2025 Jan 9. Read the full article here Protective Efficacy of Decreasing Antigen Doses of a Chlamydia abortus Subcellular Vaccine Against Ovine Enzootic Abortion in a Pregnant Sheep Challenge Model Researchers from the Moredun Research Institute, along with Biomathematics and Statistics Scotland, have been looking into the cause of ovine enzootic abortion - Chlamydia abortus. Although the disease can be controlled using commercial inactivated and live whole-organism vaccines, there are issues with both, particularly concerning efficacy and safety. Recently, there has been development of a new COMC (chlamydial outer membrane complex) vaccine. In this study, researchers evaluated the COMC vaccine in a dose-response titration of the chlamydial antigen content of the vaccine using an established pregnant sheep challenge model. They found no abortions occurred in the 15 and 10 µg groups. The abortion rates (0-14%) were significantly below that of the challenge control group (33%) and thus the results show that a dose of 10 µg antigen in the vaccine will be optimal in terms of maximising efficacy. Citation: Mak NSC, Liu J, Zhang D, Taylor J, Li X, Rahman K, Chen F, Datta SAK, Lai KK, Shi Z, Temperton N, Irving AT, Compton AA, Sloan RD. PLoS Pathog. 2024 Dec 26. Read the full article here Publication date 27 Jan, 2025
