Critical Crystal-Bacteria and Host Interactions Contributing to Kidney Stone Formation

About This Grant

PROJECT SUMMARY This study aims to understand kidney stone formation by examining interactions between calcium oxalate (CaOx) crystals, bacteria, and host factors, with certain bacterial genes playing crucial roles. Kidney stones are increasingly common, especially among children, and current treatments have remained unchanged since the 1960s, focusing on preventing crystal formation rather than addressing the mechanisms that turn crystals into complex stones. Research has identified bacteria like Enterobacteriaceae in kidney stones, with experiments showing E. coli increases CaOx deposits in mice. The urinary microbiome differs in stone formers compared to healthy individuals, with some bacteria promoting stone formation and others offering protection. Genetic sequencing found two biofilm-related genes consistently present in stone-associated bacteria, suggesting potential targets for new treatments. Host immune proteins also contribute to stone formation, with stones containing layers of crystals and organic material. Preliminary data show certain proteins are more active when both E. coli and CaOx are present, forming layered stones. The hypothesis is that interactions between CaOx crystals, immune proteins, and bacteria facilitate stone formation. Aim 1 involves measuring how stone matrix proteins and bacteria interact to promote stone formation, while Aim 2 focuses on studying biofilm-related genes in stone-associated bacteria, using genomics and transcriptomics to identify and validate these genes. This research could lead to innovative treatments targeting specific bacterial genes and mechanisms to prevent and treat kidney stones.