Blocking Binding of Bacteria to Fibrinogen Prevents Biofilm Formation and Catheter-Associated Bladder Infection in Mice
By LabMedica International staff writers Posted on 30 Sep 2014 |
Image: To adhere to catheters and start urinary tract infections, bacteria extend microscopic fibers with sticky proteins at their ends. Researchers have developed a vaccine that blocks the EbpA protein, visible as a white bulge above, and stops infections in mice (Photo courtesy of Dr. John Heuser, Washington University School of Medicine).
A team of molecular microbiologists has identified and targeted a critical step in biofilm formation and developed a vaccine that prevents catheter-associated urinary tract infections in mice.
Enterococci bacteria are a frequent cause of catheter-associated urinary tract infections, the most common type of hospital-acquired infection. Treatment has become increasingly difficult due to the emergence of multiantibiotic-resistant enterococcal strains and their ability to form biofilms on catheters. Furthermore, the insertion of a catheter into the bladder provokes an inflammatory response that results in the catheter being covered with the blood-clotting protein fibrinogen, which shields bacteria from the antibiotics.
Investigators at the Washington University School of Medicine (St. Louis, MO, USA) worked with a mouse model that demonstrated formation of catheter-associated biofilms by Enterococcus faecalis.
They reported in the September 17, 2014, online edition of the journal Science Translational Medicine that biofilm formation depended on EbpA, which is the minor subunit at the tip of a heteropolymeric surface fiber known as the endocarditis- and biofilm-associated pilus (Ebp).
EbpA is a protein of the adhesin family that mediates bacterial attachment to host fibrinogen, which is released and deposited on catheters after introduction of the catheter into the mouse bladder. Fibrinogen-binding activity resides in the amino-terminal domain of EbpA (EbpANTD), and vaccination with EbpA and EbpANTD, but not its carboxyl-terminal domain or other Ebp subunits, inhibited biofilm formation in vivo and protected against catheter-associated urinary tract infection.
Analyses in vitro demonstrated that anti-bacterial protection was associated with a serum antibody response that blocked EbpA binding to fibrinogen and the formation of a fibrinogen-dependent biofilm on catheters.
“Catheter-associated urinary tract infections are very common,” said first author, Dr. Ana Lidia Flores-Mireles, a postdoctoral research associate in molecular microbiology at the Washington University School of Medicine. “Antibiotic resistance is increasing rapidly in the bacteria that cause these infections, so developing new treatments is a priority.”
“We took a closer look at this protein and found that one-half of it is essential for binding to fibrinogen to induce infections,” said Dr. Flores-Mireles. “This protein is like the anchor of a boat. Without the anchor, the infection is at the mercy of the waves and gets washed away. The segment of genetic code that makes this part of the protein is also found in the genes of many other bacteria that cause urinary tract infections, so a vaccine, antibody, or drug that blocks this part of the protein may help prevent other infections linked to catheters in the urinary tract and in other parts of the body.”
Related Links:
Washington University School of Medicine
Enterococci bacteria are a frequent cause of catheter-associated urinary tract infections, the most common type of hospital-acquired infection. Treatment has become increasingly difficult due to the emergence of multiantibiotic-resistant enterococcal strains and their ability to form biofilms on catheters. Furthermore, the insertion of a catheter into the bladder provokes an inflammatory response that results in the catheter being covered with the blood-clotting protein fibrinogen, which shields bacteria from the antibiotics.
Investigators at the Washington University School of Medicine (St. Louis, MO, USA) worked with a mouse model that demonstrated formation of catheter-associated biofilms by Enterococcus faecalis.
They reported in the September 17, 2014, online edition of the journal Science Translational Medicine that biofilm formation depended on EbpA, which is the minor subunit at the tip of a heteropolymeric surface fiber known as the endocarditis- and biofilm-associated pilus (Ebp).
EbpA is a protein of the adhesin family that mediates bacterial attachment to host fibrinogen, which is released and deposited on catheters after introduction of the catheter into the mouse bladder. Fibrinogen-binding activity resides in the amino-terminal domain of EbpA (EbpANTD), and vaccination with EbpA and EbpANTD, but not its carboxyl-terminal domain or other Ebp subunits, inhibited biofilm formation in vivo and protected against catheter-associated urinary tract infection.
Analyses in vitro demonstrated that anti-bacterial protection was associated with a serum antibody response that blocked EbpA binding to fibrinogen and the formation of a fibrinogen-dependent biofilm on catheters.
“Catheter-associated urinary tract infections are very common,” said first author, Dr. Ana Lidia Flores-Mireles, a postdoctoral research associate in molecular microbiology at the Washington University School of Medicine. “Antibiotic resistance is increasing rapidly in the bacteria that cause these infections, so developing new treatments is a priority.”
“We took a closer look at this protein and found that one-half of it is essential for binding to fibrinogen to induce infections,” said Dr. Flores-Mireles. “This protein is like the anchor of a boat. Without the anchor, the infection is at the mercy of the waves and gets washed away. The segment of genetic code that makes this part of the protein is also found in the genes of many other bacteria that cause urinary tract infections, so a vaccine, antibody, or drug that blocks this part of the protein may help prevent other infections linked to catheters in the urinary tract and in other parts of the body.”
Related Links:
Washington University School of Medicine
Latest BioResearch News
- Genome Analysis Predicts Likelihood of Neurodisability in Oxygen-Deprived Newborns
- Gene Panel Predicts Disease Progession for Patients with B-cell Lymphoma
- New Method Simplifies Preparation of Tumor Genomic DNA Libraries
- New Tool Developed for Diagnosis of Chronic HBV Infection
- Panel of Genetic Loci Accurately Predicts Risk of Developing Gout
- Disrupted TGFB Signaling Linked to Increased Cancer-Related Bacteria
- Gene Fusion Protein Proposed as Prostate Cancer Biomarker
- NIV Test to Diagnose and Monitor Vascular Complications in Diabetes
- Semen Exosome MicroRNA Proves Biomarker for Prostate Cancer
- Genetic Loci Link Plasma Lipid Levels to CVD Risk
- Newly Identified Gene Network Aids in Early Diagnosis of Autism Spectrum Disorder
- Link Confirmed between Living in Poverty and Developing Diseases
- Genomic Study Identifies Kidney Disease Loci in Type I Diabetes Patients
- Liquid Biopsy More Effective for Analyzing Tumor Drug Resistance Mutations
- New Liquid Biopsy Assay Reveals Host-Pathogen Interactions
- Method Developed for Enriching Trophoblast Population in Samples