MnTE-2-PyP disrupts Staphylococcus aureus biofilms in a novel fracture model.
bone
infection
therapeutics
treatment
Journal
Journal of orthopaedic research : official publication of the Orthopaedic Research Society
ISSN: 1554-527X
Titre abrégé: J Orthop Res
Pays: United States
ID NLM: 8404726
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
05
12
2020
received:
13
06
2020
accepted:
16
12
2020
pubmed:
22
12
2020
medline:
19
4
2022
entrez:
21
12
2020
Statut:
ppublish
Résumé
Biofilm-associated infections in orthopedic surgery lead to worse clinical outcomes and greater morbidity and mortality. The scope of the problem encompasses infected total joints, internally fixed fractures, and implanted devices. Diagnosis is difficult. Cultures are often negative, and antibiotic treatments are ineffective. The infections resist killing by the immune system and antibiotics. The organized matrix structure of extracellular polymeric substances within the biofilm shields and protects the bacteria from identification and immune cell action. Bacteria in biofilms actively modulate their redox environment and can enhance the matrix structure by creating an oxidizing environment. We postulated that a potent redox-active metalloporphyrin MnTE-2-PyP (chemical name: manganese (II) meso-tetrakis-(N-methylpyridinium-2-yl) porphyrin) that scavenges reactive species and modulates the redox state to a reduced state, would improve the effect of antibiotic treatment for a biofilm-associated infection. An infected fracture model with a midshaft femoral osteotomy was created in C57B6 mice, internally fixed with an intramedullary 23-gauge needle and seeded with a biofilm-forming variant of Staphylococcus aureus. Animals were divided into three treatment groups: control, antibiotic alone, and combined antibioticplus MnTE-2-PyP. The combined treatment group had significantly decreased bacterial counts in harvested bone, compared with antibiotic alone. In vitro crystal violet assay of biofilm structure and corresponding nitroblue tetrazolium assay for reactive oxygen species (ROS) demonstrated that MnTE-2-PyP decreased the biofilm structure and reduced ROS in a correlated and dose-dependent manner. The biofilm structure is redox-sensitive in S. aureus and an ROS scavenger improved the effect of antibiotic therapy in model of biofilm-associated infections.
Substances chimiques
Anti-Bacterial Agents
0
Metalloporphyrins
0
Reactive Oxygen Species
0
manganese tetrakis-(N-ethyl-2 pyridyl) porphyrin
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2439-2445Informations de copyright
© 2020 Orthopaedic Research Society. Published by Wiley Periodicals LLC.
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