Staphylococcus aureus Cell Wall Biosynthesis Modulates Bone Invasion and Osteomyelitis Pathogenesis

• DOI: 10.3389/fmicb.2021.723498
• Publication Date: 2021-08-16T09:44:41Z
• Authors: Elysia A. Masters; Gowrishankar Muth...; Lananh Ho; Ann Lindley Gill; Karen L. de Mesy ...; Chad A. Galloway; James L. McGrath; Hani A. Awad; Steven R. Gill; Edward M. Schwarz
• Keywords: autolysin; 0303 health sciences; 03 medical and health sciences; surface adhesion; osteomyelitis; cell wall; S. aureus; PBP 3; Microbiology; QR1-502; 3. Good health

Staphylococcus aureus invasion of the osteocyte lacuno-canalicular network (OLCN) is a novel mechanism bacterial persistence and immune evasion in chronic osteomyelitis. Previous work highlighted S. cell wall transpeptidase, penicillin binding protein 4 (PBP4), surface adhesin, C (SasC), as critical factors for deformation propagation through nanopores vitro , representative confined canaliculi vivo . Given these findings, we hypothesized that synthesis machinery adhesins enable durotaxis- haptotaxis-guided OLCN, respectively. Here, investigated select mutants (Δpbp3, Δatl, ΔmreC) adhesin (ΔclfA ΔsasC) nanopore osteomyelitis pathogenesis In evaluation microfluidic silicon membrane-canalicular array (μSiM-CA) showed pbp3 atl clfA sasC deletion reduced propagation. Using murine model implant-associated osteomyelitis, proteins were found to be key modulators pathogenesis, while had minimal effects. Specifically, decreased septic implant loosening abscess formation medullary cavity, no significant differences. Further, peri-implant osteolysis, osteoclast activity, receptor activator nuclear factor kappa-B ligand (RANKL) production following deletion. Most notably, transmission electron microscopy (TEM) imaging infected bone was only gene herein associated with submicron Together, results demonstrate enzymes are OLCN