title: Evidence of Staphylococcus Aureus Deformation, Proliferation, and Migration in Canaliculi of Live Cortical Bone in Murine Models of Osteomyelitis.
abstract: Although Staphylococcus aureus osteomyelitis is considered to be incurable, the major bacterial reservoir in live cortical bone has remained unknown. In addition to biofilm bacteria on necrotic tissue and implants, studies have implicated intracellular infection of osteoblasts and osteocytes as a mechanism of chronic osteomyelitis. Thus, we performed the first systematic transmission electron microscopy (TEM) studies to formally define major reservoirs of S. aureus in chronically infected mouse (Balb/c J) long bone tissue. Although rare, evidence of colonized osteoblasts was found. In contrast, we readily observed S. aureus within canaliculi of live cortical bone, which existed as chains of individual cocci and submicron rod-shaped bacteria leading to biofilm formation in osteocyte lacunae. As these observations do not conform to the expectations of S. aureus as non-motile cocci 1.0 to 1.5 μm in diameter, we also performed immunoelectron microscopy (IEM) following in vivo BrdU labeling to assess the role of bacterial proliferation in canalicular invasion. The results suggest that the deformed bacteria: (1) enter canaliculi via asymmetric binary fission; and (2) migrate toward osteocyte lacunae via proliferation at the leading edge. Additional in vitro studies confirmed S. aureus migration through a 0.5-μm porous membrane. Collectively, these findings define a novel mechanism of bone infection, and provide possible new insight as to why S. aureus implant-related infections of bone tissue are so challenging to treat. © 2016 American Society for Bone and Mineral Research.
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.|Department of Pathology & Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.|Department of Orthopaedics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Karen L
authors.initials: KL
authors.lastname: de Mesy Bentley
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.|Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Trombetta
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Kohei
authors.initials: K
authors.lastname: Nishitani
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Sheila N
authors.initials: SN
authors.lastname: Bello-Irizarry
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Ninomiya
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Longze
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Hung Li
authors.initials: HL
authors.lastname: Chung
authors.affiliation: Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: McGrath
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Daiss
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.|Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Hani A
authors.initials: HA
authors.lastname: Awad
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.|Department of Orthopaedic Surgery, Virginia Commonwealth University Medical Center, Richmond, VA, USA.
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Kates
authors.affiliation: University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.|Department of Pathology & Laboratory Medicine, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.|Department of Orthopaedics, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.|Department of Biomedical Engineering, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
authors.forename: Edward M
authors.initials: EM
authors.lastname: Schwarz
mesh_terms: D000818:Animals; D000071538:Cortical Bone / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010019:Osteomyelitis / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D013203:Staphylococcal Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D013211:Staphylococcus aureus / Q000235:genetics / Q000378:metabolism*
keywords: CANALICULAR SYSTEM; CORTICAL BONE; DUROTAXIS; ELECTRON MICROSCOPY; HAPTOTAXIS; OSTEOMYELITIS; STAPHYLOCOCCUS AUREUS