Table_4_New perspectives on an old grouping: The genomic and phenotypic variability of Oxalobacter formigenes and the implications for calcium oxalate stone prevention.xlsx

Oxalobacter formigenes is a unique bacterium with the ability to metabolize oxalate as a primary carbon source. Most kidney stones in humans are composed of calcium and oxalate. Therefore, supplementation with an oxalate-degrading bacterium may reduce stone burden in patients suffering from recurrent calcium oxalate-based urolithiasis. Strains of O. formigenes are divided into two groups: group I and group II. However, the differences between strains from each group remain unclear and elucidating these distinctions will provide a better understanding of their physiology and potential clinical applications. Here, genomes from multiple O. formigenes strains underwent whole genome sequencing followed by phylogenetic and functional analyses. Genetic differences suggest that the O. formigenes taxon should be divided into an additional three species: Oxalobacter aliiformigenes sp. nov, Oxalobacter paeniformigenes sp. nov, and Oxalobacter paraformigenes sp. nov. Despite the similarities in the oxalyl-CoA gene (oxc), which is essential for oxalate degradation, these strains have multiple unique genetic features that may be potential exploited for clinical use. Further investigation into the growth of these strains in a simulated fecal environment revealed that O. aliiformigenes strains are capable of thriving within the human gut microbiota. O. aliiformigenes may be a better therapeutic candidate than current group I strains (retaining the name O. formigenes), which have been previously tested and shown to be ineffective as an oral supplement to mitigate stone disease. By performing genomic analyses and identifying these novel characteristics, Oxalobacter strains better suited to mitigation of calcium oxalate-based urolithiasis may be identified in the future.

产甲酸草酸杆菌（Oxalobacter formigenes）是一类特殊的细菌，能够以草酸作为主要碳源进行代谢。人类绝大多数肾结石由钙与草酸构成，因此补充降解草酸的细菌或可减轻复发性草酸钙性尿路结石患者的结石负荷。产甲酸草酸杆菌的菌株可分为两组：I组与II组。然而，两组菌株间的差异尚不明确，阐明这些差异有助于更好地理解其生理学特性与潜在临床应用价值。本研究对多株产甲酸草酸杆菌的基因组开展全基因组测序，并进行系统发育与功能分析。遗传学差异分析显示，产甲酸草酸杆菌类群可进一步划分为3个新种：类甲酸草酸杆菌（Oxalobacter aliiformigenes sp. nov）、近甲酸草酸杆菌（Oxalobacter paeniformigenes sp. nov）以及副甲酸草酸杆菌（Oxalobacter paraformigenes sp. nov）。尽管负责草酸降解的关键基因草酰辅酶A基因（oxalyl-CoA gene, oxc）序列相似，但这些菌株具备多项独特的遗传特征，有望应用于临床。对这些菌株在模拟粪便环境中的生长特性进行进一步研究后发现，类甲酸草酸杆菌能够在人类肠道菌群中存活增殖。类甲酸草酸杆菌或比现有I组菌株（仍保留产甲酸草酸杆菌的学名）更适合作为治疗候选菌株——此前针对I组菌株的临床试验显示，其作为口服补充剂无法有效缓解结石病症。通过基因组分析与这些新特征的发掘，未来或可筛选出更适配草酸钙性尿路结石缓解治疗的草酸杆菌菌株。