Ona Rogiers1,2,3,4, Michelle Holtappels1,2, Wafi Siala5,6, Mohamed Lamkanfi3,4, Françoise Van Bambeke5, Katrien Lagrou7, Patrick Van Dijck1,2, Sona Kucharíková1,2. 1. VIB-KU Leuven Center for Microbiology, Kasteelpark Arenberg 31, Leuven, Belgium. 2. Laboratory of Molecular Cell Biology, Institute of Botany and Microbiology, KU Leuven, Kasteelpark Arenberg 31, Leuven, Belgium. 3. Center for Inflammation Research, VIB, Technologiepark 927, Zwijnaarde, Belgium. 4. Department of Internal Medicine, Ghent University, Technologiepark 927, Zwijnaarde, Belgium. 5. Pharmacologie cellulaire et moléculaire, Louvain Drug Research Institute Université catholique de Louvain, Avenue Mounier 73/B1.73.05, 1200 Woluwe-Saint-Lambert, Brussels, Belgium. 6. OneLIFE S.A., Avenue Albert Einstein, 15, Louvain-la-Neuve, Belgium. 7. KU Leuven, Department of Microbiology and Immunology Laboratory of Clinical Bacteriology and Mycology, UZ Herestraat 49, Leuven, Belgium.
Abstract
Objectives: We aimed to establish a novel murine intra-abdominal foreign body infection model to study the activity of anidulafungin and tigecycline against dual species Candida albicans/Staphylococcus aureus biofilms. Methods: In vitro and in vivo single and dual species biofilms were developed inside serum-coated triple-lumen catheters placed in 24-well plates or implanted intraperitoneally in BALB/c mice. The effect of tigecycline and anidulafungin alone and in combination was tested using clinically relevant concentrations. Scanning electron microscopy was used to visualize the mature biofilm structure developed intraperitoneally. Flow cytometry was used to determine the immunological response upon infection. Immunoblot analysis allowed us to determine the effect of anidulafungin on poly-β-(1,6)-N-acetylglucosamine in in vitro-grown S. aureus biofilms. Results: We determined the MIC, MBC and in vitro susceptibility profile for anidulafungin and tigecycline against C. albicans and S. aureus in mixed and single species biofilms. We demonstrated that anidulafungin acts synergistically when combined with tigecycline against in vivo intra-abdominal biofilms. Moreover, we reveal that anidulafungin reduces the abundance of S. aureus poly-β-(1,6)-N-acetylglucosamine. The influx of neutrophils is much increased when infected with mixed biofilms compared with single species biofilms. Conclusions: Currently, treatment of intra-abdominal infections, in particular polymicrobial catheter-associated peritonitis, is ineffective. To the best of our knowledge, this is the first study that provides insight into new possible options for treatment of C. albicans/S. aureus biofilms present in the abdominal cavity.
Objectives: We aimed to establish a novel murineintra-abdominal foreign body infection model to study the activity of anidulafungin and tigecycline against dual species Candida albicans/Staphylococcus aureus biofilms. Methods: In vitro and in vivo single and dual species biofilms were developed inside serum-coated triple-lumen catheters placed in 24-well plates or implanted intraperitoneally in BALB/c mice. The effect of tigecycline and anidulafungin alone and in combination was tested using clinically relevant concentrations. Scanning electron microscopy was used to visualize the mature biofilm structure developed intraperitoneally. Flow cytometry was used to determine the immunological response upon infection. Immunoblot analysis allowed us to determine the effect of anidulafungin on poly-β-(1,6)-N-acetylglucosamine in in vitro-grown S. aureus biofilms. Results: We determined the MIC, MBC and in vitro susceptibility profile for anidulafungin and tigecycline against C. albicans and S. aureus in mixed and single species biofilms. We demonstrated that anidulafungin acts synergistically when combined with tigecycline against in vivo intra-abdominal biofilms. Moreover, we reveal that anidulafungin reduces the abundance of S. aureus poly-β-(1,6)-N-acetylglucosamine. The influx of neutrophils is much increased when infected with mixed biofilms compared with single species biofilms. Conclusions: Currently, treatment of intra-abdominal infections, in particular polymicrobial catheter-associated peritonitis, is ineffective. To the best of our knowledge, this is the first study that provides insight into new possible options for treatment of C. albicans/S. aureus biofilms present in the abdominal cavity.