Mechanisms of Immune Evasion and Bone Tissue Colonization That Make Staphylococcus aureus the Primary Pathogen in Osteomyelitis

Curr Osteoporos Rep. 2019 Dec;17(6):395-404. doi: 10.1007/s11914-019-00548-4.

Abstract

Purpose of review: Staphylococcus aureus is the primary pathogen responsible for osteomyelitis, which remains a major healthcare burden. To understand its dominance, here we review the unique pathogenic mechanisms utilized by S. aureus that enable it to cause incurable osteomyelitis.

Recent findings: Using an arsenal of toxins and virulence proteins, S. aureus kills and usurps immune cells during infection, to produce non-neutralizing pathogenic antibodies that thwart adaptive immunity. S. aureus also has specific mechanisms for distinct biofilm formation on implants, necrotic bone tissue, bone marrow, and within the osteocyte lacuno-canicular networks (OLCN) of live bone. In vitro studies have also demonstrated potential for intracellular colonization of osteocytes, osteoblasts, and osteoclasts. S. aureus has evolved a multitude of virulence mechanisms to achieve life-long infection of the bone, most notably colonization of OLCN. Targeting S. aureus proteins involved in these pathways could provide new targets for antibiotics and immunotherapies.

Keywords: Adaptive immunity; Canalicular invasion; Immune proteome; Orthopedic infections; Osteomyelitis; Staphylococcus aureus.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Abscess / immunology
  • Adaptive Immunity / immunology*
  • B-Lymphocytes / immunology
  • Biofilms
  • Bone and Bones / immunology*
  • Bone and Bones / microbiology
  • Humans
  • Immune Evasion*
  • Immunity, Cellular / immunology
  • Immunity, Humoral / immunology
  • Osteoblasts / microbiology
  • Osteoclasts / microbiology
  • Osteocytes / microbiology
  • Osteomyelitis / immunology*
  • Osteomyelitis / microbiology
  • Staphylococcal Infections / immunology*
  • Staphylococcal Infections / microbiology
  • Staphylococcal Protein A / immunology
  • Staphylococcus aureus / immunology
  • Staphylococcus aureus / pathogenicity*

Substances

  • Staphylococcal Protein A