Research focus: from chicken vaccines to the global response to AMR

Summary: Researchers from the Institute of Immunology and Infection Research, along with international collaborators, investigated U-insertion/deletion (U-indel) RNA editing in trypanosome mitochondria. They found that this process, guided by gRNAs, potentially regulates respiration in different forms. The specific proteins responsible for controlling editing and the significance of non-canonical editing are still not fully understood.

However, the study highlighted the critical role of KREH2, an associated helicase, in controlling non-canonical editing and a regulatory gRNA. Knockdown of KREH2 had varying effects on editing fidelity and RNA structure in PCF and BSF. Notably, the regulatory gRNA serves a dual function in both canonical editing and RNA structure formation.

Meehan J, McDermott SM, Ivens A, Goodall Z, Chen Z, Yu Z, Woo J, Rodshagen T, McCleskey L, Sechrist R, Stuart K, Zeng L, Rouskin S, Savill NJ, Schnaufer A, Zhang X, Cruz-Reyes J, Nucleic Acids Res. 2023 May 29;gkad453. doi: 10.1093/nar/gkad453.

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Summary: This study, which included Dr. Muwonge from the Roslin Institute, investigated EKE organisms in the maternity environment of a Ugandan referral hospital. Gram-negative bacteria, including E. coli, K. pneumoniae, and Enterobacter, were isolated from mothers, neonates, health workers, and inanimate objects. Carbapenems were effective against most isolates, but multidrug resistance was prevalent.

Analysis suggested transmission of multidrug-resistant EKE to newborns, emphasizing the need for infection prevention and antimicrobial stewardship programs to reduce the spread of drug-resistant bacteria in the hospital.

Mayanja R, Muwonge A, Aruhomukama D, Katabazi FA, Bbuye M, Kigozi E, Nakimuli A, Sekikubo M, Najjuka CF, Kateete DP, PLoS One. 2023 Jun 8;18(6):e0286955. doi: 10.1371/journal.pone.0286955.

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Summary: In collaboration with the School of Biological Sciences, the Roslin Institute conducted a study on Campylobacter jejuni, a leading cause of bacterial gastroenteritis. Previous research has highlighted the effectiveness of glycoconjugate vaccines containing C. jejuni N-glycan in reducing caecal colonisation in chickens. The study aimed to assess the efficacy of live E. coli expressing the N-glycan and glycosylated OMVs derived from them against different C. jejuni strains.

Surprisingly, despite the presence of the C. jejuni N-glycan on the surface of both the live strain and OMVs, no reduction in caecal colonisation by C. jejuni was observed, and specific responses to the N-glycan were not detected.

Vohra P, Bremner A, Nicholls B, Chintoan-Uta C, Corona-Torres R, Stevens MP, Vaccine. 2023 Jun 29;41(29):4295-4301.doi:10.1016/j.vaccine.2023.05.046.

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Summary: Researchers from the Institute of Evolutionary Biology and Royal (Dick) School of Veterinary Studies explored virus host shifts and their role in emerging infectious diseases. They investigated the susceptibility of 64 Staphylococcaceae bacteria strains to bacteriophage ISP, a potential phage therapy. Host phylogeny was found to significantly influence susceptibility, both within and among species. Assessment methods showed varying correlations, indicating limitations of plaque assays alone.

Predicting susceptibility based on phylogenetic relationships proved generally effective, except in cases where phylogeny provided no informative data. These findings enhance our understanding of phage infections and their impact on virus host shifts.

Walsh SK, Imrie RM, Matuszewska M, Paterson GK, Weinert LA, D Hadfield JD, Buckling A, Longdon B, PLoS Pathog. 2023 Jun 8;19(6):e1011433. doi: 10.1371/journal.ppat.1011433.

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Summary: In a collaborative effort led by researchers from the Usher Institute, a comprehensive analysis of 114 national action plans (NAPs) on antimicrobial resistance was conducted across 114 countries. Utilizing a governance framework encompassing 18 domains and 54 indicators, the study evaluated policy design, implementation tools, and monitoring and evaluation strategies.

The mean antimicrobial resistance governance score was 51, with Norway achieving the highest score of 85, while the Federated States of Micronesia obtained the lowest score of 28. Participation domain scored highest at 83, whereas accountability and feedback mechanism domains scored the lowest, both at 30. Policy design and implementation tools domains exhibited similar scores (54), whereas monitoring and evaluation efforts were relatively lower at 38.

These findings emphasize the urgency for enhanced international efforts and improved monitoring to effectively address the extensive impact and severity of antimicrobial resistance.

Patel J, Harant A, Fernandes G, Mwamelo AJ, Hein W, Dekker D, Sridhar D, Lancet Infect Dis. 2023 Jun;23(6):706-718. doi: 10.1016/S1473-3099(22)00796-4.

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Summary: Inconsistent findings exist regarding the association between RSV subgroup distribution and timing of RSV seasonal epidemics. A global-level analysis, conducted with the assistance of the Usher Institute, considered meteorological factors and compiled data from 36 studies in 20 countries.

RSV subgroup distribution had minimal impact on seasonal characteristics globally. The joint influence of subgroup distribution and meteorological factors explained only a small portion of the variation. Further studies should explore population susceptibility, mobility, and viral interference.

Deng S, Ling Guo, Cohen C, Meijer A, Moyes J, Pasittungkul S, Poovorawan Y, Teirlinck A, van Boven M, Wanlapakorn N, Wolter N, Paget J, Nair H, Li Y, for Respiratory Virus Global Epidemiology Network and PROMISE investigators, J Infect Dis. 2023 May 30;jiad192. doi: 10.1093/infdis/jiad192.

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Summary: Respiratory syncytial virus (RSV) causes lower respiratory tract infections in adults, leading to hospitalizations. Another study conducted by the Usher Institute estimated RSV-associated hospitalizations in Europe. Among adults aged 18 years and above, there are approximately 158,229 (95% CI: 140,865-175,592) hospitalizations annually, with 92% occurring in adults aged 65 years and above. The annual average hospitalizations for adults aged 75-84 years is estimated at 74,519 (69,923-79,115), and for those aged 85 years and above, it is 37,904 (32,444-43,363). These estimates highlight the significant burden of RSV-associated hospitalizations in adults, comparable to that in young children.

Osei-Yeboah R, Spreeuwenberg P, Del Riccio M, Fischer TK, Egeskov-Cavling AM, Bøås H, van Boven M, Wang X, Lehtonen T, Bangert M, Campbell H, Paget J; RESCEU investigators, J Infect Dis. 2023 May 29;jiad189. doi: 10.1093/infdis/jiad189.

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Summary: 

Researchers investigated S. pyogenes colonization and serological responses in children receiving LAIV or no intervention. Nasopharyngeal swabs were collected at baseline, day 7, and day 21 to detect colonization, and anti-streptococcal IgG levels were measured, including in children acquiring S. pyogenes during the study.

Colonization prevalence ranged from 7-13%. LAIV group children showed a higher likelihood of colonization over time. Significant IgG level increases were observed after asymptomatic colonization, particularly for M1 and SpyCEP proteins.

These findings suggest a modest increase in asymptomatic S. pyogenes colonization with LAIV and highlight its immunological implications. The study, including researchers from the Centre for Inflammation Research, underscores the potential of LAIV for studying interactions between influenza and S. pyogenes.

Keeley AJ, Groves D, Armitage EP, Senghore E, Jagne YJ, Sallah HJ, Drammeh S, Angyal A, Hornsby H, de Crombrugghe G, Smeesters PJ, Rossi O, Carducci M, Peno C, Bogaert D, Kampmann B, Marks M, Shaw HA, Turner CR, de Silva TI, MRCG Strep A Study Group, J Infect Dis. 2023 May 29;jiad153. doi: 10.1093/infdis/jiad153.

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Summary: Teladorsagia circumcincta is a parasitic nematode that affects small ruminant production. Due to drug resistance, developing a vaccine is crucial. In a recent study conducted by Moredun Research Institute, a recombinant subunit vaccine was effective in reducing egg excretion and worm burden in Canaria Hair Breed (CHB) lambs, but not in Canaria Sheep (CS). Transcriptomic analysis of abomasal lymph nodes revealed different immune responses between CHB and CS. CHB lambs exhibited type-2 immune responses and genes related to tissue repair, while CS showed downregulation of inflammation and immune response.

These findings contribute to vaccine refinement and understanding variations in immune response among young lambs.

Pérez-Hernández T, Hernández JN, Machín C, McNeilly TN, Nisbet AJ, Matthews JB, Burgess STG, González JF, Vet Parasitol. 2023 May 29;320:109960. doi: 10.1016/j.vetpar.2023.109960.

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