Oxalobacter formigenes

The genome of O. formigenes has been sequenced by at least three different researchers. It has a G+C content of 49.6%.^[9][11]

Based on fatty acid profile, 16S ribosomal RNA sequencing, and DNA probes specific to the oxc (oxalyl-CoA decarboxylase) gene and frc (formyl-CoA transferase), O. formigenes has been divided into two groups.^{[1][12][13][14]} Group 1 has less diversity and better growth compared to group 2. To date, most research has focused on group 1 strains due to their ease of growth.

Interestingly, analysis with the DNA probes showed that group 2 may be further divided into two subgroups.^[13] Whole genome sequencing has revealed that the original O. formigenes taxon can be divided into three additional species: Oxalobacter aliiformigenes, Oxalobacter paeniformigenes, and Oxalobacter paraformigenes.^[11]

O. formigenes uses oxalate as its primary carbon source.^[1] Oxalate is absorbed through an oxalate:formate antiporter (OxlT) in a 1:1 proportion.^[15] Imported oxalate is then converted to oxalyl-CoA via formyl-CoA transferase (frc). Oxalyl-CoA is decarboxylated using and H⁺ via oxalyl-CoA decarboxylase (oxc), releasing CO₂, and generating formyl-CoA, which is used for the frc reaction. In total, approximately 1 mol of formate and CO₂ are produced per mol of oxalate consumed.^[16] 3H⁺ are imported via an ATPase to provide H⁺ for the decarboxylation reaction.^[17]

Biomass in O. formigenes is primarily generated by oxalate consumption through the metabolism of oxalyl-CoA in the glycerate pathway.^[18][19] Acetate and carbonate are also used for cell biomass, but to a lesser extent than oxalate.^[18]

O. formigenes was isolated in oxalate-containing anerobic media.^[1] Currently, O. formigenes is grown in anaerobic Hungate tubes using a CO₂-bicarbonate buffered oxalate media.^[2] Optimal growth is achieved at a pH between 6 and 7. Oxalate is used at 20 mM for freezer recovery and general maintenance but concentrations can be increased to 100 mM for increased cell density. While oxalate is the main carbon source, small amounts of acetate and yeast extract are supportive of growth.^[2][16] O. formigenes can reach stationary phase in approximately 24 – 48 hours but is sometimes delayed to 72 hours.

Enriched anaerobic complex media (e.g. Brain heart infusion) fail to support the growth of O. formigenes unless supplemented with oxalate. Therefore, these media can be used to assess the purity of O. formigenes cultures.

Given the fastidious nature of O. formigenes, traditional methods for antibiotic susceptibility testing are not sufficient. Instead, bacteria are cultured in the presence of antibiotics and screened for viability using opaque anaerobic oxalate agar.^[2][20][21] This method demonstrated that O. formigenes is resistant to nalidixic acid, ampicillin, amoxicillin, streptomycin, and vancomycin.^[20][21] O. formigenes was also found to be susceptible to ciprofloxacin, clarithromycin, clindamycin, doxycycline, gentamicin, levofloxacin, metronidazole, and tetracycline.^[20][21]

O. formigenes is found in the mammalian gastrointestinal tract and often isolated from feces. In addition to culture-based methods, O. formigenes is presence is detected using molecular methods such as qPCR and next generation sequencing.

Humans are not typically born with O. formigenes and only become colonized when they begin crawling around in their environment.^[22] In adulthood, the frequency of O. formigenes in the gut microbiota varies across different populations. In North India, O. formigenes is prevalent in approximately 65% of the population.^[23] In South Korea and Japan, O. formigenes is present in about 75% of individuals.^[24][25] In the United States of America, O. formigenes is only detected in about 30% of the human population.^[26][27] Populations who do not practice modern medicine or life in a Western lifestyle typically have an increased prevalence of O. formigenes, which could imply that these practices affect O. formigenes colonization.^[28][29]

The idea that ruminants are colonized by oxalate-degrading bacteria came from the observation that sheep grazing on oxalate-rich plants (e.g. Halogeton glomeratus) consumed large quantities of this plant and died of renal intoxication from oxalate.^[2] However, by slowly acclimatizing sheep to high-oxalate intake, they would survive the consumption of large quantities of oxalate-rich plants.^[30] This led to the proposal that resident oxalate-degrading bacteria were enriched by the gradual introduction to an oxalate-rich diet, which protected the sheep from oxalate-induced renal damage.^[31][32] In 1980, the first oxalate-degrading bacteria were isolated from the rumen of sheep, and it was later named Oxalobacter formigenes.^[1][16]