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Staphylococcus aureus Infects Osteoclasts and Replicates Intracellularly.

Jennifer L Krauss1, Philip M Roper1, Anna Ballard1

  • 1Division of Bone & Mineral Diseases, Musculoskeletal Research Center, Washington University School of Medicine, Saint Louis, Missouri, USA.

Mbio
|October 17, 2019
PubMed
Summary

Staphylococcus aureus can infect and multiply within osteoclasts, the bone-resorbing cells, unlike macrophages. This intracellular bacterial proliferation in osteoclasts may drive osteomyelitis progression and recurrence.

Keywords:
RANKLStaphylococcus aureusboneintracellular bacteriaosteoclastsosteomyelitis

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Area of Science:

  • Microbiology
  • Immunology
  • Bone Biology

Background:

  • Osteomyelitis (OM) is bone inflammation often caused by Staphylococcus aureus.
  • While osteoblasts are known targets, osteoclast involvement in OM pathogenesis is unclear.
  • S. aureus infection of osteoclasts could explain OM recurrence and chronicity.

Purpose of the Study:

  • To investigate the potential for Staphylococcus aureus to infect and replicate within osteoclasts.
  • To determine the role of osteoclast differentiation and signaling in S. aureus intracellular survival.
  • To elucidate the contribution of osteoclasts to Staphylococcus aureus evasion of immune responses.

Main Methods:

  • Osteoclasts (OCs) differentiated from bone marrow macrophages (BMMs) using RANKL.
  • Intracellular survival assays and flow cytometry to quantify bacterial burden.
  • Confocal and time-lapse microscopy to visualize intracellular infection and phagolysosome colocalization.
  • Manipulation of NFATc1 and alternative NF-κB signaling pathways.

Main Results:

  • Staphylococcus aureus successfully infected and replicated within mature osteoclasts.
  • Intracellular bacterial growth in OCs correlated with NFATc1 levels.
  • Bacterial burden decreased in BMMs, indicating selective OC susceptibility.
  • Reduced phagolysosome colocalization observed in infected OCs.

Conclusions:

  • Osteoclasts serve as a niche for Staphylococcus aureus intracellular proliferation.
  • This intracellular survival mechanism in OCs may promote OM progression and immune evasion.
  • Osteoclasts play a previously unrecognized role in the pathogenesis of osteomyelitis.