Institute of Microbiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.
Service of Infectious Diseases, Department of Medicine, Lausanne University Hospital, Lausanne, Switzerland.
Sci Rep. 2024 Aug 27;14(1):19804. doi: 10.1038/s41598-024-70608-y.
Fusobacterium necrophorum is a Gram-negative anaerobic bacterium responsible for localized infections of the oropharynx that can evolve into bacteremia and/or septic thrombophlebitis of the jugular vein or peritonsillar vein, called Lemierre's syndrome. To identify microbial genetic determinants associated with the severity of this life-threatening disease, 70 F. necrophorum strains were collected and grouped into two categories according to the clinical presentation: (i) localized infection, (ii) bacteremia with/without Lemierre's syndrome. Comparative genomic analyses revealed two clades with distinct genetic content, one clade being significantly enriched with isolates from subjects with bacteremia. To identify genetic determinants contributing to F. necrophorum pathogenicity, genomic islands and virulence factor orthogroups (OVFs) were predicted. The presence/absence profiles of OVFs did not group isolates according to their clinical category, but rather according to their phylogeny. However, a variant of lktA, a key virulence factor, with a frameshift deletion that results in two open reading frames, was associated with bacteremia. Moreover, a genome-wide association study identified three orthogroups associated with bacteremic strains: (i) cas8a1, (ii) a sodium/solute symporter, and (iii) a POP1 domain-containing protein. Further studies must be performed to assess the functional impact of lktA mutation and of these orthogroups on the physiopathological mechanisms of F. necrophorum infections.
败毒梭菌是一种革兰氏阴性厌氧菌，可引起口咽部局部感染，进而发展为败血性颈静脉或扁桃体周静脉血栓性静脉炎，即莱姆病综合征。为了确定与这种危及生命疾病严重程度相关的微生物遗传决定因素，我们收集了 70 株败毒梭菌，并根据临床表现将其分为两类：（i）局部感染，（ii）菌血症伴/不伴莱姆病综合征。比较基因组分析揭示了两个具有不同遗传组成的分支，其中一个分支显著富集了来自菌血症患者的分离株。为了确定导致败毒梭菌致病性的遗传决定因素，我们预测了基因组岛和毒力因子直系同源群（OVFs）。OVFs 的存在/缺失谱并未根据临床类别对分离株进行分组，而是根据其系统发育进行分组。然而，lktA 的一个变体，即关键毒力因子，具有移码缺失导致两个开放阅读框，与菌血症相关。此外，全基因组关联研究确定了与菌血症菌株相关的三个直系同源群：（i）cas8a1，（ii）一种钠/溶质转运体，和（iii）一种含有 POP1 结构域的蛋白质。需要进一步研究来评估 lktA 突变和这些直系同源群对败毒梭菌感染生理病理机制的功能影响。
