Parvathi S Kumar1, Clifford T Mauriello2, Pamela S Hair3, Nicholas S Rister4, Courtney Lawrence5, Reem H Raafat6, Kenji M Cunnion7. 1. 855 W. Brambleton Avenue, Eastern Virginia Medical School, Norfolk, VA 23507, USA. Electronic address: Parvathi.kumar@chkd.org. 2. 855 W. Brambleton Avenue, Eastern Virginia Medical School, Norfolk, VA 23507, USA. Electronic address: Clifford.Mauriello@SanfordHealth.org. 3. 855 W. Brambleton Avenue, Eastern Virginia Medical School, Norfolk, VA 23507, USA. Electronic address: hairps@evms.edu. 4. 855 W. Brambleton Avenue, Eastern Virginia Medical School, Norfolk, VA 23507, USA. Electronic address: Nicholas.rister@chkd.org. 5. 855 W. Brambleton Avenue, Eastern Virginia Medical School, Norfolk, VA 23507, USA. Electronic address: mslawrence@gmail.com. 6. 601Children's lane Division of Nephrology, Children's Hospital of The King's Daughters, Norfolk, VA 23507, USA. Electronic address: reem.raafat@chkd.org. 7. 855 W. Brambleton Avenue, Eastern Virginia Medical School, Norfolk, VA 23507, USA; 601Children's lane, Division of Infectious diseases, Children's Hospital of The King's Daughters, Norfolk, VA 23507, USA. Electronic address: cunniokm@evms.edu.
Abstract
BACKGROUND: Staphylococcus aureus peritonitis is a serious complication of Chronic Peritoneal Dialysis (CPD) and associated with a higher risk for severe and recurrent infections compared with other bacteria. We have previously shown that complement-mediated effectors essential for optimal opsonophagocytosis of S. aureus are inhibited by high glucose concentrations. Since most commonly used peritoneal dialysis (PD) fluids are glucose-based, we hypothesized that glucose-based PD fluids likely inhibit complement host defenses against S. aureus. METHODS: Commercially available PD fluids were tested: glucose-based (Dianeal), Dianeal supplemented with amino acids, icodextrin-based (Extraneal) and amino acid-based (Nutrineal). Control PD fluid was generated to simulate Dianeal excluding the glucose. Three commercially available glucose concentrations were tested: Dianeal 1.5% (15 gm/1000 ml), Dianeal 2.5% (25 gm/1000 ml) and Dianeal 4.25% (42.5 gm/1000 ml). Complement effectors against S. aureus were analyzed including opsonization with C3-fragments, anaphylatoxin generation, and phagocytosis efficiency. We also evaluated clinical strains, including MRSA strains, and specific complement activation pathways. RESULTS: Glucose-based PD fluids inhibited complement opsonization of S. aureus (≥7-fold reduction) and inhibited S. aureus-induced generation of anaphylatoxins C3a and C5a (>10-fold reduction) compared to non-glucose based PD fluids. Dianeal 1.5%, 2.5% and 4.25%, all similarly inhibited C3-mediated opsonization. Glucose-based PD fluids showed a ≥4-fold reduction in opsonization of clinical strains of S.aureus, including MRSA strains. Decreased opsonization of S.aureus in the glucose-based PD fluid compared with non-glucose based fluids correlated with decreased phagocytosis by neutrophils. CONCLUSION: Complement-mediated opsonophagocytosis of S. aureus and anaphylatoxin generation were severely inhibited in glucose-based PD fluids compared with non-glucose-based PD fluids. By inhibiting complement host defenses, glucose-based PD fluids may increase the risk of and severity of S. aureus peritonitis for CPD patients using these fluids.
BACKGROUND:Staphylococcus aureus peritonitis is a serious complication of Chronic Peritoneal Dialysis (CPD) and associated with a higher risk for severe and recurrent infections compared with other bacteria. We have previously shown that complement-mediated effectors essential for optimal opsonophagocytosis of S. aureus are inhibited by high glucose concentrations. Since most commonly used peritoneal dialysis (PD) fluids are glucose-based, we hypothesized that glucose-based PD fluids likely inhibit complement host defenses against S. aureus. METHODS: Commercially available PD fluids were tested: glucose-based (Dianeal), Dianeal supplemented with amino acids, icodextrin-based (Extraneal) and amino acid-based (Nutrineal). Control PD fluid was generated to simulate Dianeal excluding the glucose. Three commercially available glucose concentrations were tested: Dianeal 1.5% (15 gm/1000 ml), Dianeal 2.5% (25 gm/1000 ml) and Dianeal 4.25% (42.5 gm/1000 ml). Complement effectors against S. aureus were analyzed including opsonization with C3-fragments, anaphylatoxin generation, and phagocytosis efficiency. We also evaluated clinical strains, including MRSA strains, and specific complement activation pathways. RESULTS:Glucose-based PD fluids inhibited complement opsonization of S. aureus (≥7-fold reduction) and inhibited S. aureus-induced generation of anaphylatoxins C3a and C5a (>10-fold reduction) compared to non-glucose based PD fluids. Dianeal 1.5%, 2.5% and 4.25%, all similarly inhibited C3-mediated opsonization. Glucose-based PD fluids showed a ≥4-fold reduction in opsonization of clinical strains of S.aureus, including MRSA strains. Decreased opsonization of S.aureus in the glucose-based PD fluid compared with non-glucose based fluids correlated with decreased phagocytosis by neutrophils. CONCLUSION: Complement-mediated opsonophagocytosis of S. aureus and anaphylatoxin generation were severely inhibited in glucose-based PD fluids compared with non-glucose-based PD fluids. By inhibiting complement host defenses, glucose-based PD fluids may increase the risk of and severity of S. aureus peritonitis for CPDpatients using these fluids.
Authors: Kenji M Cunnion; Neel K Krishna; Haree K Pallera; Angela Pineros-Fernandez; Magdielis Gregory Rivera; Pamela S Hair; Brittany P Lassiter; Ryan Huyck; Mary A Clements; Antoinette F Hood; George T Rodeheaver; Patrick S Cottler; Jerry L Nadler; Anca D Dobrian Journal: PLoS One Date: 2017-01-20 Impact factor: 3.240