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Evidence of Staphylococcus Aureus Deformation, Proliferation, and Migration in Canaliculi of Live Cortical Bone in Murine Models of Osteomyelitis
Author(s) -
de Mesy Bentley Karen L,
Trombetta Ryan,
Nishitani Kohei,
BelloIrizarry Sheila N,
Ninomiya Mark,
Zhang Longze,
Chung Hung Li,
McGrath James L,
Daiss John L,
Awad Hani A,
Kates Stephen L,
Schwarz Edward M
Publication year - 2017
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3055
Subject(s) - bone canaliculus , staphylococcus aureus , osteocyte , osteomyelitis , cortical bone , bone infection , microbiology and biotechnology , bone cell , biology , biofilm , pathology , bacteria , osteoblast , medicine , immunology , in vitro , biochemistry , genetics
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.