Investigation of the antimicrobial susceptibility, virulence determinants and phylogenetics of clinical Fusobacterium necrophorum strains isolated at the UK Anaerobe Reference Laboratory over four decades (1982-2019)

Abstract

Fusobacterium necrophorum is a strict anaerobic Gram-negative rod, which causes a wide range of infections. The clinical spectrum varies substantially, from asymptomatic carriage, to easily treated pharyngitis and life-threatening septic thrombophlebitis, with devastating and long-lasting sequelae. Despite a myriad of published case reports and scientific papers, relatively little is understood about the antimicrobial susceptibility, pathogenesis and phylogeny of F. necrophorum, due to the rarity of severe disease and difficulty growing and characterising the bacterium. Whole genome multi-locus sequence (wgMLST) and single nucleotide polymorphism (SNP) typing of nearly 400 F. necrophorum strains showed a high degree of congruence and indicates that F. necrophorum is likely a transmissible pathogen. The existence of clade- and subspecies-specific virulence genes amongst strains confirm some of the findings of smaller studies, although contrasting results were also noted. Associations of known virulence determinants with disease state or decade of isolation were not found, indicating that host factors have an important part to play in F. necrophorum pathogenicity and should be investigated further. Agreement between antimicrobial resistance phenotype and genotype was observed for clindamycin and tetracyclines. Antimicrobial susceptibility analysis of strains tested between 2016 and 2021 (n=313) revealed resistance to antimicrobials commonly recommended for F. necrophorum antibiotic chemotherapy, particularly penicillin. Absence of genomic clustering amongst resistant study isolates suggests there hasn’t been clonal spread of resistance genes over time. Additional antibiotic susceptibility surveillance and exploration of clinical breakpoints, along with treatment outcomes, is essential to inform upcoming evidence-based therapeutic guidance. A paucity of UK-based F. necrophorum patient experience media and information have been highlighted. Given the potentially lifelong, and life-limiting, impact of severe disease on people, and their families, this is an important area for forthcoming research and publication to ensure there is a patient-centred approach to F. necrophorum infection in the future.

Date of Award	20 Jun 2024
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Philip Day (Supervisor)