Intracellular Staphylococcus aureus and antibiotic resistance: Implications for treatment of staphylococcal osteomyelitis

Journal of Orthopaedic Research - Tập 24 Số 1 - Trang 87-93 - 2006
J. Kent Ellington1, Mitchel B. Harris2, Michael Hudson3, Sonia Vishin3, Lawrence X. Webb4, Robert J. Sherertz5
1Department of Orthopaedic Surgery, Carolinas Medical Center, 1000 Blythe Boulevard, Charlotte, North Carolina 28223, USA.
2Department of Orthopaedic Surgery, Harvard Medical School, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts 02115. Telephone: 617‐732‐5385; Fax: 617‐732‐6937
3Department of Biology, UNC Charlotte, 9201 University City Boulevard, Charlotte, North Carolina 28223
4Department of Orthopaedic Surgery, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, North Carolina 27103
5Department of Infectious Disease, Wake Forest University School of Medicine, Medical Center Boulevard, Winston Salem, North Carolina 27103

Tóm tắt

AbstractStaphylococcus aureus is responsible for 80% of human osteomyelitis. It can invade and persist within osteoblasts. Antibiotic resistant strains of S. aureus make successful treatment of osteomyelitis difficult. Null Hypothesis: antibiotic sensitivities of S. aureus do not change after exposure to the osteoblast intracellular environment. Human and mouse osteoblast cultures were infected and S. aureus cells were allowed to invade. Following times 0, 12, 24, and 48 h ( ± the addition of erythromycin, clindamycin, and rifampin at times 0 or 12 h), the osteoblasts were lysed and intracellular bacteria enumerated. Transmission electron microscopy was performed on extracellular and intracellular S. aureus cells. In mouse osteoblasts, administration of bacteriostatic antibiotics at time 0 prevented the increase in intracellular S. aureus. If the antibiotics were delayed 12 h, this did not occur. When rifampin (bactericidal) was introduced at time 0 to human and mouse osteoblasts, there was a significant decrease in number of intracellular S. aureus within osteoblasts compared to control. If rifampin was delayed 12 h, this did not occur. Significant time‐dependent S. aureus structural changes were observed after exposure to the osteoblast intracellular environment. These studies demonstrate that once S. aureus is established intracellularly for 12 h, the bacteria are less sensitive to antibiotics capable of eukaryotic cell penetration (statistically significant). These antibiotic sensitivity changes could be due in part to the observed structural changes. This leads to the rejection of our null hypotheses that the antibiotic sensitivities of S. aureus are unaltered by their location. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

Từ khóa


Tài liệu tham khảo

10.1056/NEJM197001222820406

10.1093/clinids/10.6.1102

10.1097/00003086-199708000-00030

10.1111/j.1365-2958.1994.tb01046.x

Cheung AI, 1995, Cloning expression and nucleotide sequence of a Staphylococcus aureus gene (fbpA) encoding a fibrinogen‐binding protein, Infect Immun, 63, 1914, 10.1128/iai.63.5.1914-1920.1995

10.1002/j.1460-2075.1987.tb02511.x

10.1111/j.1432-1033.1991.tb16468.x

10.1111/j.1365-2958.1994.tb00304.x

McGavin MH, 1993, Identification of a Staphylococcus aureus extracellular matrix‐binding protein with broad specificity, Infect Immun, 61, 2479, 10.1128/iai.61.6.2479-2485.1993

10.1074/jbc.271.26.15803

Patti JM, 1992, Molecular characterization and expression of a gene encoding a Staphylococcus aureus collagen adhesin, J Biol Chem, 267, 4766, 10.1016/S0021-9258(18)42898-0

10.1007/s007740050040

10.1002/jbmr.5650100509

10.1006/mpat.1999.0272

10.1006/mpat.1995.0075

10.1128/IAI.67.5.2677-2681.1999

10.1016/S8756-3282(99)00239-2

10.1128/IAI.69.3.1581-1586.2001

10.1128/IAI.68.9.5075-5083.2000

10.1089/107999001300177484

10.1086/315138

10.1128/IAI.69.9.5235-5242.2001

10.1128/IAI.71.3.1209-1216.2003

10.1111/j.1574-6968.2000.tb09096.x

Gillaspy AF, 1996, Role of the accessory gene regulator (agr) in pathogenesis of staphylococcal osteomyelitis, Infect Immun, 63, 3373, 10.1128/iai.63.9.3373-3380.1995

10.1086/315138

Wilson CB, 1982, Gentamicin is inactive against bacteria sequestered in the eucaryotic intracellular environment. Cellular antibiotic pharmacology, Semin Perinatol, 6, 205

10.1139/m87-025

10.1128/AAC.17.4.591

10.1093/infdis/132.5.493

10.1128/AAC.44.9.2276-2285.2000

10.1089/mdr.1996.2.239

10.1128/iai.43.3.825-833.1984

de Jonge BL, 1992, Peptidoglycan composition in heterogeneous Tn551 mutants of a methicillin‐resistant Staphylococcus aureus strain, J Biol Chem, 267, 11255, 10.1016/S0021-9258(19)49904-3

Ellington JK, 2003, Intracellular Staphylococcus aureus. A mechanism for the indolence of osteomyelitis, J Bone Joint Surg Br, 85, 918, 10.1302/0301-620X.85B6.13509

Thông tin
Thông tin xuất bản

Journal of Orthopaedic Research

Tập 24 Số 1

87-93

Thông tin tác giả