An in vitro platform for elucidating the molecular genetics of S. aureus invasion of the osteocyte lacuno-canalicular network during chronic osteomyelitis

Nanomedicine. 2019 Oct:21:102039. doi: 10.1016/j.nano.2019.102039. Epub 2019 Jun 24.

Abstract

Staphylococcus aureus osteomyelitis is a devasting disease that often leads to amputation. Recent findings have shown that S. aureus is capable of invading the osteocyte lacuno-canalicular network (OLCN) of cortical bone during chronic osteomyelitis. Normally a 1 μm non-motile cocci, S. aureus deforms smaller than 0.5 μm in the sub-micron channels of the OLCN. Here we present the μSiM-CA (Microfluidic - Silicon Membrane - Canalicular Array) as an in vitro screening platform for the genetic mechanisms of S. aureus invasion. The μSiM-CA platform features an ultrathin silicon membrane with defined pores that mimic the openings of canaliculi. While we anticipated that S. aureus lacking the accessory gene regulator (agr) quorum-sensing system would not be capable of invading the OLCN, we found no differences in propagation compared to wild type in the μSiM-CA. However the μSiM-CA proved predictive as we also found that the agr mutant strain invaded the OLCN of murine tibiae.

Keywords: Accessory gene regulator; Bone on a chip; Osteomyelitis; Silicon nanomembrane; Staphylococcus aureus.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cortical Bone / microbiology
  • Cortical Bone / pathology
  • Humans
  • Mice
  • Osteocytes / microbiology*
  • Osteocytes / pathology
  • Osteomyelitis / genetics*
  • Osteomyelitis / microbiology
  • Osteomyelitis / pathology
  • Quorum Sensing / genetics
  • Staphylococcal Infections / genetics*
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / pathology
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / pathogenicity*

Supplementary concepts

  • Chronic recurrent multifocal osteomyelitis