Introduction: Oxalobacter formigenes is a near-ubiquitous bacterium with the unique ability to metabolize oxalate as a sole carbon source. Due to this metabolic function, O. formigenes has a historically complex relationship with stone disease. However, because this organism is known to colonize both stone formers and healthy controls, its role in mitigating stone disease is uncertain. Based on genomic and phenotypic analyses, O. formigenes has been divided into two groups. Oral supplementation to mitigate stone formation has only been tested with group 1 (G1) strains and has demonstrated mixed results. The differences between G1 and group 2 (G2) strains remain unclear. Elucidating these distinctions could provide a better understanding of the physiology and potential clinical applications of the bacterium.
Methods: By combining computational genomics with culture-dependent techniques, we sought to characterize the group differences that exist between strains of O. formigenes. Whole genomes isolated from multiple strains of O. formigenes were sequenced and combined with existing genome assemblies to functionally characterize the strains. In vitro growth curves were used to determine the ability of these strains to use oxalate individually. To investigate how Oxalobacter functions in a diverse microbial setting, a human fecal sample was inoculated into media with or without oxalate and the bacterial community dynamics were monitored over time via 16S rRNA gene sequencing.
Results: Phylogenetic analysis confirmed a high degree of intergroup dissimilarity between G1 and G2 strains. G1 strains were found to have a lower GC content, larger genomes, more functional genes, and increased intragroup similarity when compared to the G2 strains. Interestingly, no genes were identified as unique to animal strains. G1 strains grew faster and to higher cell density than G2 strains. Oxalobacter abundance did not significantly increase in the oxalate fecal bacterial consortium over time, but the community composition significantly changed.
Conclusions: These findings highlight that G1 strains are highly related and may have an enhanced capability to degrade oxalate. With respect to survival and colonization, the diversity of G2 strains could provide increased adaptability, a benefit to potential future G2-based therapeutics such as oral supplementation to stone-formers. Additionally, the lack of major differences between human and animal strains indicates that non-human isolates should also be considered as a candidate intervention for stone disease.
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.jpg "John Chmiel, MSC photo")