Research focus: from canine infections to assessing the impact of HPV Vaccine in Scotland
A compilation of notable publication highlights from the Edinburgh Infectious Diseases network over the past month.
Rapid metagenomic sequencing for diagnosis and antimicrobial sensitivity prediction of canine bacterial infections
Summary: Antimicrobial resistance is a major threat to human and animal health, requiring appropriate antimicrobial use. Traditional culture and sensitivity testing take 48-72 hours, leading to the use of broad-spectrum antimicrobials. Researchers from The Roslin Institute and Royal (Dick) School of Veterinary Studies, present a rapid, culture-free diagnostics pipeline using metagenomic nanopore sequencing from clinical urine and skin samples of dogs.
Their approach identifies bacterial pathogens within 5 hours, including difficult-to-culture species and predict antibiotic sensitivity with up to 95% accuracy for urine samples. Skin swabs may require an additional host depletion step due to higher host DNA. This pipeline facilitates individually tailored veterinary treatment plans on the same day, promoting better antimicrobial stewardship.
Ring N, Low AS, Wee B, Paterson GK, Nuttall T, Gally D, Mellanby R, Fitzgerald JR, Microb Genom. 2023 Jul;9(7). doi: 10.1099/mgen.0.001066.
Estimating long-term vaccine effectiveness against SARS-CoV-2 variants: a model-based approach
Summary: The Institute of Immunology and Infection Research studied vaccine effectiveness against SARS-CoV-2 and its variants. They found sustained protection against Omicron for six months after the third vaccine dose, but it gradually wanes after a year. Administering a variant-matched vaccine as the fourth dose, targeting Omicron BA.1/2, could prevent almost twice as many hospitalizations and deaths compared to using the ancestral vaccine.
However, uncertainties remain about using immunogenicity data to predict vaccine effectiveness and the impact of infection-induced immunity on future efficacy.
Hogan AB, Wu SL, Doohan P, Olivera Mesa D, Toor J, Watson OJ, Winskill P, Charles G, Barnsley G, Riley EM, Khoury DS, Ferguson NM, Ghani AC, Nat Commun. 2023 Jul 19;14(1):4325. doi: 10.1038/s41467-023-39736-3.
Environmentally sensitive photosensitizers enable targeted photodynamic ablation of Gram-positive antibiotic resistant bacteria
Summary: Researchers from the Centre for Inflammation Research and the Institute for Regeneration and Repair have developed a promising approach to tackle bacterial infections. These infections pose significant challenges to human health, causing millions of deaths annually due to high antibiotic usage and antimicrobial resistance.
The researchers used nitrobenzoselenadiazoles, environmentally sensitive organic photosensitizers, to create theranostics with light-controlled antimicrobial activity. By combining these agents with bacteria-targeting moieties, they produced effective photodynamic agents that could visualize and eradicate multidrug-resistant Gram-positive pathogens, including biofilm-forming strains. This chemical strategy offers a potential solution for developing new antimicrobial therapies to combat refractory bacterial infections.
Benson S, Kiang A, Lochenie C, Lal N, Mohanan SMPC, Williams GOS, Dhaliwal K, Mills B, Vendrell M, Theranostics. 2023 Jun 26;13(11):3814-3825. doi: 10.7150/thno.84187. eCollection 2023.
Microbiotoxicity: antibiotic usage and its unintended harm to the microbiome
Summary: This review, led by the Centre for Inflammation Research, examines the association between antibiotic use and the development of antimicrobial resistance and microbiome dysregulation, which can lead to adverse health outcomes. The authors analyze recent interventional studies and clinical evidence to shed light on the potential risks of antibiotics on a patient's microbiome.
They propose the term "microbiotoxicity" to describe the unintended harms of antibiotics on the microbiome. The review offers a framework for clinicians to consider the microbiotoxic effects when prescribing antibiotics, alongside their intended benefits. While more causal evidence is needed, the growing body of research underscores the importance of understanding the impact of antibiotics on the microbiome.
Theodosiou AT, Jones CE, Read RC, Bogaert D, Curr Opin Infect Dis. 2023 Jul 19. doi: 10.1097/QCO.0000000000000945.
Self-Adjuvanting Calcium-Phosphate-Coated Microcrystal-Based Vaccines Induce Pyroptosis in Human and Livestock Immune Cells
Summary: Researchers investigated the potential of calcium phosphate-modified protein-coated microcrystals (CaP-PCMCs) as a self-adjuvanting vaccine delivery system. CaP-PCMCs have shown enhanced antigen-specific IgG responses in mice. In this study, they explored the interaction between CaP-PCMCs and mammalian immune cells in vitro. Incubation with CaP-PCMCs induced rapid pyroptosis in immune cells from cattle, sheep, and humans, accompanied by interleukin-1β release and Caspase-1 activation.
The researchers from the Moredun Foundation and Royal (Dick) School of Veterinary Studies found that this pyroptosis was cell-CaP-PCMCs contact dependent. Results support CaP-PCMCs as a promising vaccine antigen delivery system, particularly for subunit vaccines requiring enhanced adaptive immunity.
Corripio-Miyar Y, MacLeod CL, Mair I, Mellanby RJ, Moore BD, McNeilly TN, Vaccines (Basel). 2023 Jul 11;11(7):1229. doi: 10.3390/vaccines11071229.
The changing nature of HPV associated with high grade cervical lesions in vaccinated populations, a retrospective study of over 1700 cases in Scotland
Summary: A recent study examined over 1700 CIN cases (2011-2017) in young women, jointly conducted by the Scottish HPV Lab, Edinburgh Research Facility and Public Health Scotland. The focus was on HPV 16/18 in relation to vaccination and birth year. The study revealed that vaccinated CIN2 cases had fewer instances of HPV 16/18/31/33 & 45 (with odds ratios of 0.3 & 0.4).
Interestingly, vaccinated CIN2+ cases showed a rise in other HPV types. This shift suggests potential vaccine impact, possibly reducing the progression of CIN2+. These findings hold significant implications for redefining measures related to high-grade diseases.
Cuschieri K , Palmer T, Graham C, Cameron R, Roy K, Br J Cancer. 2023 Aug 10. doi: 10.1038/s41416-023-02386-9.
Nanoscaled Discovery of a Shunt Rifamycin from Salinispora arenicola Using a Three-Color GFP-Tagged Staphylococcus aureus Macrophage Infection Assay
Summary: Antimicrobial resistance poses a global health threat, necessitating urgent development of novel treatments against multi-drug resistant bacteria. Staphylococcus aureus, a significant pathogen in humans and animals, is linked to high morbidity and mortality worldwide. This bacterium's ability to survive within macrophages hinders immune response, promotes dissemination, and undermines antibiotics.
Researchers from the School of Biological Sciences and Roslin Institute collaborated on a study introducing a confocal fluorescence imaging assay, which uses green fluorescent protein (GFP)-tagged S. aureus, to detect macrophage infection and identify potential antibiotics. This approach, combined with nanoscaled chemical analysis, led to the discovery of an active rifamycin analogue—a promising antimicrobial compound with macrophage intracellular activity. This finding presents a significant stride in combating the looming challenge of antimicrobial resistance.
Pham NT, Alves J, Sargison FA , Cullum R, Wildenhain J, Fenical W, Butler MS, Mead DA, Duggan BM, Fitzgerald JR, La Clair JJ, Auer M, ACS Infect Dis. 2023 Aug 11;9(8):1499-1507. doi: 10.1021/acsinfecdis.3c00049.
Distinctive hospital and community resistomes in Scottish urban wastewater: Metagenomics of a paired wastewater sampling design
Summary: Scientists from the Roslin Institute and Usher Institute studied wastewater to learn about resistant bacteria, focusing on hospitals. They compared different places in Scotland – hospitals, communities, and mixed wastewater. Hospitals had more resistant genes, like a storehouse. But further downstream, treatment plants made the "hospital" sign weaker. This shows differences in resistance and how wastewater changes.
Lepper HC, Perry MR, Wee BA , Wills D, Nielsen H, Saria Otani S, Simon M, Aarestrup FM, Woolhouse MEJ , van Bunnik BAD, Sci Total Environ. 2023 Aug 4;165978. doi: 10.1016/j.scitotenv.2023.165978.
Comparison of multiple international metrics for benchmarking antibiotic usage (ABU) using UK beef and sheep data
Summary: Accurate monitoring of antibiotic usage (ABU) in livestock is vital for national antibiotic stewardship. Various ABU metrics exist, but their comparability is unclear. Policymakers require a grasp of metric relationships for effective regulation and international trade.
Led by the Royal (Dick) School of Veterinary Studies, this study analyzes >16,200 antibiotic sales to 686 UK farms, revealing ABU variations among farm types. Metrics alignment was observed (>0.9), demonstrating their reliability in benchmarking. This reassures farmers and facilitates global trade negotiations, where ABU rankings can influence subsidies, penalties, and import/export access for livestock products between countries.
Davies P, Hyde R, Corbishley A, J Antimicrob Chemother. 2023 Aug 16;dkad259. doi: 10.1093/jac/dkad259.