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Endotoxin and nanobacteria in polycystic kidney disease
J T Hjelle1, M A Miller-Hjelle, I R Poxton
1Departments of Biomedical and Therapeutic Sciences, Pathology, and Surgery, University of Illinois College of Medicine at Peoria, Peoria, Illinois 61656, USA. Hjelle@uic.edu
Background:
Microbes have been suspected as provocateurs of polycystic kidney disease (PKD), but attempts to isolate viable organisms have failed. Bacterial endotoxin is the most often reported microbial product found in PKD fluids. We assessed potential microbial origins of endotoxin in cyst fluids from 13 PKD patients and urines of PKD and control individuals.
Methods:
Fluids were probed for endotoxin and nanobacteria, a new bacterium, by the differential Limulus Amebocyte Lysate assay (dLAL), genus-specific antilipopolysaccharide (LPS) antibodies, monoclonal antibodies to nanobacteria, and hyperimmune serum to Bartonella henselae (HS-Bh). Selected specimens were also assessed by transmission electron microscopy (TEM) and nanobacterial culture methods.
Results:
LPS or its antigenic metabolites were found in more than 75% of cyst fluids tested. Nanobacteria were cultured from 11 of 13 PKD kidneys, visualized in 8 of 8 kidneys by TEM, and immunodetected in all 13 PKD kidneys. By immunodetection, nanobacterial antigens were found in urine from 7 of 7 PKD males, 1 of 7 PKD females, 3 of 10 normal males, and 1 of 10 normal females. "Nanobacterium sanguineum" was dLAL positive and cross-reactive with antichlamydial LPS and HS-Bh. Some cyst fluids were also positive for LPS antigens from Escherichia coli, Bacteroides fragilis and/or Chlamydia, and HS-Bh, as were liver cyst fluids from one patient. Tetracycline and citrate inhibited nanobacterial growth in vitro.
Conclusion:
Nanobacteria or its antigens were present in PKD kidney, liver, and urine. The identification of candidate microbial pathogens is the first step in ascertaining their contribution, if any, to human disease.
Insights
Researchers found evidence of nanobacteria and bacterial endotoxin in polycystic kidney disease (PKD) cyst fluids and urine. This suggests a potential microbial link to PKD, warranting further investigation into these pathogens.
Area of Science:
- Microbiology
- Nephrology
- Pathogen Discovery
Background:
- Microbial involvement in polycystic kidney disease (PKD) is suspected but unproven.
- Previous studies reported bacterial endotoxin in PKD fluids, but viable organisms were not isolated.
- This study investigated potential microbial origins of endotoxin in PKD cyst fluids and urine.
Purpose of the Study:
- To assess the presence and origin of microbial products, specifically endotoxin and nanobacteria, in PKD cyst fluids and urine.
- To identify potential microbial pathogens contributing to PKD.
- To explore the characteristics and detection methods for nanobacteria in PKD samples.
Main Methods:
- Differential Limulus Amebocyte Lysate assay (dLAL) and genus-specific antilipopolysaccharide (LPS) antibodies were used to detect endotoxin.
- Monoclonal antibodies to nanobacteria and hyperimmune serum to Bartonella henselae (HS-Bh) were employed for immunodetection.
- Transmission electron microscopy (TEM) and nanobacterial culture methods were utilized for visualization and isolation.
Main Results:
- LPS or antigenic metabolites were detected in over 75% of PKD cyst fluids.
- Nanobacteria were cultured, visualized by TEM, and immunodetected in PKD kidneys and cyst fluids.
- Nanobacterial antigens were found in urine of PKD patients, with varying prevalence by sex, and in some healthy individuals.
Conclusions:
- Nanobacteria or their antigens were identified in PKD kidney, liver, and urine samples.
- This study provides the first identification of candidate microbial pathogens in PKD.
- Further research is needed to ascertain the contribution of these identified microbes to human PKD.