The Interaction between Enterobacteriaceae and Calcium Oxalate Deposits

• Published in: PloS one 2015-10, Vol.10 (10), p.e0139575-e0139575
• Main Authors: Barr-Beare, Evan, Saxena, Vijay, Hilt, Evann E, Thomas-White, Krystal, Schober, Megan, Li, Birong, Becknell, Brian, Hains, David S, Wolfe, Alan J, Schwaderer, Andrew L
• Format: Article
• Language: English
• Subjects: Adolescent; Animal models; Animals; Bacteria; Calcium; Calcium oxalate; Calcium Oxalate - metabolism; Care and treatment; Child; Crystals; Deoxyribonucleic acid; Deposits; Disease Models, Animal; DNA; DNA, Bacterial - chemistry; E coli; Enterobacteriaceae; Enterobacteriaceae - genetics; Enterobacteriaceae - metabolism; Enterobacteriaceae infections; Escherichia coli; Escherichia coli - genetics; Escherichia coli - metabolism; Female; Glyoxylates - administration & dosage; Health risks; Humans; Immune response; Immune system; Immunology; In vivo methods and tests; Innate immunity; Inorganic chemistry; Kidney - immunology; Kidney - metabolism; Kidney Calculi - etiology; Kidney Calculi - metabolism; Kidney Calculi - microbiology; Kidney stones; Kidneys; Male; Medicine; Mice; Mice, Inbred C57BL; Microbiology; Nephrolithiasis; Nephrology; Nucleotide sequence; Oxalic acid; Pathogenesis; Proteins; Pyelonephritis; Pyelonephritis - etiology; Risk Factors; RNA, Ribosomal, 16S - chemistry; RNA, Ribosomal, 16S - genetics; Sequence Analysis, DNA; Transcription; Transplants & implants; Urinary tract; Urinary tract diseases; Urinary tract infections; Urine; Urogenital system; Urolithiasis; Urolithiasis - etiology; Urology; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0139575

The role of calcium oxalate crystals and deposits in UTI pathogenesis has not been established. The objectives of this study were to identify bacteria present in pediatric urolithiasis and, using in vitro and in vivo models, to determine the relevance of calcium oxalate deposits during experimental pyelonephritis. Pediatric kidney stones and urine were collected and both cultured and sequenced for bacteria. Bacterial adhesion to calcium oxalate was compared. Murine kidney calcium oxalate deposits were induced by intraperitoneal glyoxalate injection and kidneys were transurethrally inoculated with uropathogenic Escherichia coli to induce pyelonephritis. E. coli of the family Enterobacteriaceae was identified in patients by calcium oxalate stone culture. Additionally Enterobacteriaceae DNA was sequenced from multiple calcium oxalate kidney stones. E. coli selectively aggregated on and around calcium oxalate monohydrate crystals. Mice inoculated with glyoxalate and uropathogenic E. coli had higher bacterial burdens, increased kidney calcium oxalate deposits and an increased kidney innate immune response compared to mice with only calcium oxalate deposits or only pyelonephritis. In a murine model, the presence of calcium oxalate deposits increases pyelonephritis risk, likely due to preferential aggregation of bacteria on and around calcium oxalate crystals. When both calcium oxalate deposits and uropathogenic bacteria were present, calcium oxalate deposit number increased along with renal gene transcription of inner stone core matrix proteins increased. Therefore renal calcium oxalate deposits may be a modifiable risk factor for infections of the kidney and urinary tract. Furthermore, bacteria may be present in calcium oxalate deposits and potentially contribute to calcium oxalate renal disease.