Matrix stones are a rare form of kidney stones. They feature a high percentage of hydrogel-like organic matter, and their formation is closely associated with urinary tract infections. Herein, comprehensive materials and biochemical approaches were taken to map the organic-inorganic interface and gather insights into the host-microbe interplay in pathological renal biomineralization. Surgically extracted soft and slimy matrix stones were examined using micro-X-ray computed tomography and various microspectroscopy techniques. Higher-mineral-density laminae were positive for calcium-bound Alizarin red. Lower-mineral-density laminae revealed periodic acid-Schiff-positive organic filamentous networks of varied thickness. These organic filamentous networks, which featured a high polysaccharide content, were enriched with zinc, carbon, and sulfur elements. Neutrophil extracellular traps (NETs) along with immune response-related proteins, including calprotectin, myeloperoxidase, CD63, and CD86, also were identified in the filamentous networks. Expressions of NETs and upregulation of polysaccharide-rich mucin secretion are proposed as a part of the host immune defense to "trap" pathogens. These host-microbe derived organic matrices can facilitate heterogeneous nucleation and precipitation of inorganic particulates, resulting in macroscale aggregates known as "matrix stones". These insights into the plausible aggregation of constituents through host-microbe interplay underscore the unique "double-edged sword" effect of the host immune response to pathogens and the resulting renal biominerals.
ACS nanoscience Au. 2023 Jul 07*** epublish ***
Yushi Bai, Yongmei Wang, Misun Kang, Claire M Gabe, Sudarshan Srirangapatanam, Austin Edwards, Marshall Stoller, Stefan J Green, Shaul Aloni, Nobumichi Tamura, Elia Beniash, Markus Hardt, Sunita P Ho
Department of Preventive and Restorative Dental Sciences, School of Dentistry, University of California San Francisco, San Francisco, California 94143, United States., Department of Oral and Craniofacial Sciences, School of Dentistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15213, United States., Biological Imaging Development Center, University of California San Francisco, San Francisco, California 94143, United States., Department of Urology, School of Medicine, University of California San Francisco, San Francisco, California 94143, United States., Department of Internal Medicine, Division of Infectious Diseases, Rush Medical College, Rush University, Chicago, Illinois 60612, United States., The Molecular Foundry, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States., Advanced Light Source, Lawrence Berkeley National Laboratory, Berkeley, California 94720, United States., Center for Salivary Diagnostics, The Forsyth Institute, Cambridge, Massachusetts 02142, United States.