Effect of savirin in the prevention of biofilm-related Staphylococcus aureus prosthetic joint infection
Background: Most of the arthroplasty surgery failure due to prosthetic joint infections (PJI) is caused by biofilm-associated Staphylococcus aureus. In a recent experimental study, savirin has been used to prevent and treat S. aureus skin infections in animal models. We explored the application of s...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.989417/full |
| _version_ | 1811261863404503040 |
|---|---|
| author | Narayan Pant Narayan Pant Socorro Miranda-Hernandez Catherine Rush Jeffrey Warner Damon P. Eisen |
| author_facet | Narayan Pant Narayan Pant Socorro Miranda-Hernandez Catherine Rush Jeffrey Warner Damon P. Eisen |
| author_sort | Narayan Pant |
| collection | DOAJ |
| description | Background: Most of the arthroplasty surgery failure due to prosthetic joint infections (PJI) is caused by biofilm-associated Staphylococcus aureus. In a recent experimental study, savirin has been used to prevent and treat S. aureus skin infections in animal models. We explored the application of savirin in a PJI mouse model to determine its utility as an adjunct therapy to prevent PJI.Materials and methods: The in-vitro antibacterial and antibiofilm activity of savirin, with or without antibiotics (cefazolin, rifampicin, and vancomycin), against S. aureus were investigated using broth microdilution and crystal violet staining method, respectively. The effect of savirin treatment on the expression of the key biofilm-related genes (icaA, icaD, eno, fib, ebps, and agr) in S. aureus was studied using quantitative reverse transcriptase polymerase chain reaction (qRTPCR). The in-vivo efficacy of savirin alone and with cefazolin to prevent S. aureus PJI was determined using a clinically relevant PJI mouse model. Mice were randomized into five groups (n = 8/group): 1) infected K-wire savirin treated group, 2) infected K-wire cefazolin treated group, 3) infected K-wire savirin plus cefazolin treated group, 4) infected K-wire PBS treated group, 5) sterile K-wire group. Savirin was administered subcutaneously immediately post-surgery and intravenous cefazolin was given on day seven.Results: Savirin inhibited planktonic and biofilm in-vitro growth of S. aureus, showed enhanced inhibitory activity when combined with antibiotics, and down-regulated the expression of key S. aureus biofilm-related genes (icaA, icaD, eno, fib, ebps, and agr). Savirin significantly reduced bacterial counts on joint implants in comparison with the PBS treated control, while savirin plus cefazolin reduced bacterial counts on both implants and peri-prosthetic tissues.Conclusion: Savirin adjuvant therapy may prevent biofilm formation and S. aureus PJI. This study gives baseline data for using savirin for the prevention as well as treatment of S. aureus PJI in future animal studies. |
| first_indexed | 2024-04-12T19:13:31Z |
| format | Article |
| id | doaj.art-5991067c279641f88ba7dd1fa4d0cde5 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T19:13:31Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-5991067c279641f88ba7dd1fa4d0cde52022-12-22T03:19:48ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-09-011310.3389/fphar.2022.989417989417Effect of savirin in the prevention of biofilm-related Staphylococcus aureus prosthetic joint infectionNarayan Pant0Narayan Pant1Socorro Miranda-Hernandez2Catherine Rush3Jeffrey Warner4Damon P. Eisen5College of Medicine and Dentistry, James Cook University, Townsville, QLD, AustraliaAustralian Institute of Tropical Health and Medicine, Townsville, QLD, AustraliaAustralian Institute of Tropical Health and Medicine, Townsville, QLD, AustraliaAustralian Institute of Tropical Health and Medicine, Townsville, QLD, AustraliaAustralian Institute of Tropical Health and Medicine, Townsville, QLD, AustraliaCollege of Medicine and Dentistry, James Cook University, Townsville, QLD, AustraliaBackground: Most of the arthroplasty surgery failure due to prosthetic joint infections (PJI) is caused by biofilm-associated Staphylococcus aureus. In a recent experimental study, savirin has been used to prevent and treat S. aureus skin infections in animal models. We explored the application of savirin in a PJI mouse model to determine its utility as an adjunct therapy to prevent PJI.Materials and methods: The in-vitro antibacterial and antibiofilm activity of savirin, with or without antibiotics (cefazolin, rifampicin, and vancomycin), against S. aureus were investigated using broth microdilution and crystal violet staining method, respectively. The effect of savirin treatment on the expression of the key biofilm-related genes (icaA, icaD, eno, fib, ebps, and agr) in S. aureus was studied using quantitative reverse transcriptase polymerase chain reaction (qRTPCR). The in-vivo efficacy of savirin alone and with cefazolin to prevent S. aureus PJI was determined using a clinically relevant PJI mouse model. Mice were randomized into five groups (n = 8/group): 1) infected K-wire savirin treated group, 2) infected K-wire cefazolin treated group, 3) infected K-wire savirin plus cefazolin treated group, 4) infected K-wire PBS treated group, 5) sterile K-wire group. Savirin was administered subcutaneously immediately post-surgery and intravenous cefazolin was given on day seven.Results: Savirin inhibited planktonic and biofilm in-vitro growth of S. aureus, showed enhanced inhibitory activity when combined with antibiotics, and down-regulated the expression of key S. aureus biofilm-related genes (icaA, icaD, eno, fib, ebps, and agr). Savirin significantly reduced bacterial counts on joint implants in comparison with the PBS treated control, while savirin plus cefazolin reduced bacterial counts on both implants and peri-prosthetic tissues.Conclusion: Savirin adjuvant therapy may prevent biofilm formation and S. aureus PJI. This study gives baseline data for using savirin for the prevention as well as treatment of S. aureus PJI in future animal studies.https://www.frontiersin.org/articles/10.3389/fphar.2022.989417/fullS. aureussavirinmouse modelprosthetic joint infectionadjuvant therapyarthroplasty |
| spellingShingle | Narayan Pant Narayan Pant Socorro Miranda-Hernandez Catherine Rush Jeffrey Warner Damon P. Eisen Effect of savirin in the prevention of biofilm-related Staphylococcus aureus prosthetic joint infection Frontiers in Pharmacology S. aureus savirin mouse model prosthetic joint infection adjuvant therapy arthroplasty |
| title | Effect of savirin in the prevention of biofilm-related Staphylococcus aureus prosthetic joint infection |
| title_full | Effect of savirin in the prevention of biofilm-related Staphylococcus aureus prosthetic joint infection |
| title_fullStr | Effect of savirin in the prevention of biofilm-related Staphylococcus aureus prosthetic joint infection |
| title_full_unstemmed | Effect of savirin in the prevention of biofilm-related Staphylococcus aureus prosthetic joint infection |
| title_short | Effect of savirin in the prevention of biofilm-related Staphylococcus aureus prosthetic joint infection |
| title_sort | effect of savirin in the prevention of biofilm related staphylococcus aureus prosthetic joint infection |
| topic | S. aureus savirin mouse model prosthetic joint infection adjuvant therapy arthroplasty |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.989417/full |
| work_keys_str_mv | AT narayanpant effectofsavirininthepreventionofbiofilmrelatedstaphylococcusaureusprostheticjointinfection AT narayanpant effectofsavirininthepreventionofbiofilmrelatedstaphylococcusaureusprostheticjointinfection AT socorromirandahernandez effectofsavirininthepreventionofbiofilmrelatedstaphylococcusaureusprostheticjointinfection AT catherinerush effectofsavirininthepreventionofbiofilmrelatedstaphylococcusaureusprostheticjointinfection AT jeffreywarner effectofsavirininthepreventionofbiofilmrelatedstaphylococcusaureusprostheticjointinfection AT damonpeisen effectofsavirininthepreventionofbiofilmrelatedstaphylococcusaureusprostheticjointinfection |