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

John A Chmiel; Charles Carr; Gerrit A Stuivenberg; Robertson Venema; Ryan M Chanyi; Kait F Al; Daniel Giguere; Henry Say; Polycronis P Akouris; Sergio Ari Domínguez Romero; Aaron Kwong; Vera Tai; Susan F Koval; Hassan Razvi; Jennifer Bjazevic; Jeremy P Burton

doi:10.3389/fmicb.2022.1011102

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

Front Microbiol. 2022 Dec 21:13:1011102. doi: 10.3389/fmicb.2022.1011102. eCollection 2022.

Authors

John A Chmiel^{1

2}, Charles Carr³, Gerrit A Stuivenberg^{1

2}, Robertson Venema⁴, Ryan M Chanyi⁵, Kait F Al^{1

2}, Daniel Giguere⁶, Henry Say⁶, Polycronis P Akouris^{1

2}, Sergio Ari Domínguez Romero⁶, Aaron Kwong⁷, Vera Tai⁶, Susan F Koval¹, Hassan Razvi⁸, Jennifer Bjazevic⁸, Jeremy P Burton^{1

2

8}

Affiliations

¹ Department of Microbiology and Immunology, Western University, London, ON, Canada.
² Canadian Centre for Human Microbiome and Probiotics Research, London, ON, Canada.
³ Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.
⁴ Department of Medicine, The University of British Columbia, Vancouver, BC, Canada.
⁵ School of Veterinary Science, Massey University, Palmerston North, New Zealand.
⁶ Department of Biology, Western University, London, ON, Canada.
⁷ Department of Medicine, Western University, London, ON, Canada.
⁸ Division of Urology, Department of Surgery, Western University, London, ON, Canada.

Abstract

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.

Keywords: Oxalobacter formigenes; gut microbiome; kidney stone disease; nephrolithiasis and hyperoxaluria; oxalate degradation; phylogenomic and comparative genomic analyses; revised taxonomy.