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

Muthukrishnan, Gowrishankar; Masters, Elysia A; Daiss, John L.; Schwarz, Edward M.

doi:10.1007/s11914-019-00548-4

Cited by 108 publications

(111 citation statements)

References 115 publications

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“…While this work has identified the autolysin antigens as potential targets (27,(41)(42)(43), it also identified IsdB as the most immunodominant antigen (17). Our clinical research approach has been focused on elucidating the immune proteome against S. aureus in patients with MSKI and correlating their humoral immunity with their clinical outcome (16,17,(19)(20)(21)(44)(45)(46). While this work also found autolysin antigens to have human vaccine potential, we also found a clear signal that humoral immunity against IsdB is associated with poor clinical outcomes, including amputation and septic death (16,17,20).…”

Section: Discussionmentioning

confidence: 99%

IsdB antibody–mediated sepsis following S. aureus surgical site infection

Nishitani¹,

Ishikawa²,

Morita³

et al. 2020

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Section: Discussionmentioning

confidence: 99%

IsdB antibody–mediated sepsis following S. aureus surgical site infection

Nishitani¹,

Ishikawa²,

Morita³

et al. 2020

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“…S . aureus persistence in chronic osteomyelitis can be attributed to a variety of immune evasion mechanisms specific to the bone microenvironment [ 12 , 13 ]. These mechanisms include Staphylococcus abscess communities (SACs) within the bone marrow and soft tissue [ 14 – 16 ], biofilm formation on necrotic tissue and implant hardware when present [ 17 , 18 ], and most notably, invasion and colonization of the immune-privileged osteocyte lacuno-canalicular network (OLCN) of cortical bone [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Identification of Penicillin Binding Protein 4 (PBP4) as a critical factor for Staphylococcus aureus bone invasion during osteomyelitis in mice

et al. 2020

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Staphylococcus aureus infection of bone is challenging to treat because it colonizes the osteocyte lacuno-canalicular network (OLCN) of cortical bone. To elucidate factors involved in OLCN invasion and identify novel drug targets, we completed a hypothesis-driven screen of 24 S. aureus transposon insertion mutant strains for their ability to propagate through 0.5 μm-sized pores in the Microfluidic Silicon Membrane Canalicular Arrays (μSiM-CA), developed to model S. aureus invasion of the OLCN. This screen identified the uncanonical S. aureus transpeptidase, penicillin binding protein 4 (PBP4), as a necessary gene for S. aureus deformation and propagation through nanopores. In vivo studies revealed that Δpbp4 infected tibiae treated with vancomycin showed a significant 12-fold reduction in bacterial load compared to WT infected tibiae treated with vancomycin (p<0.05). Additionally, Δpbp4 infected tibiae displayed a remarkable decrease in pathogenic bone-loss at the implant site with and without vancomycin therapy. Most importantly, Δpbp4 S. aureus failed to invade and colonize the OLCN despite high bacterial loads on the implant and in adjacent tissues. Together, these results demonstrate that PBP4 is required for S. aureus colonization of the OLCN and suggest that inhibitors may be synergistic with standard of care antibiotics ineffective against bacteria within the OLCN.

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“…Biofilms are notably involved in osteomyelitis, an infection of the bone characterized by bacterial colonization leading to inflammatory reaction and the resorption of bone [ 23 ]. The bacterial presence can be due to an adjacent contaminated bone, a bacteremia, or a colonized implant [ 24 ]. The latter, named Prosthetic Joint Infections or Periprosthetic Joint Infections (PJIs), is defined as an osteomyelitis infection characterized by a post-operative infection that occurs after the prosthetic joint surgery [ 24 ].…”

Section: Role Of Bacterial Biofilm In Prosthetic Joint Infectionsmentioning

confidence: 99%

Antibiotic Tolerance of Staphylococcus aureus Biofilm in Periprosthetic Joint Infections and Antibiofilm Strategies

et al. 2020

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The need for bone and joint prostheses is currently growing due to population aging, leading to an increase in prosthetic joint infection cases. Biofilms represent an adaptive and quite common bacterial response to several stress factors which confer an important protection to bacteria. Biofilm formation starts with bacterial adhesion on a surface, such as an orthopedic prosthesis, further reinforced by matrix synthesis. The biofilm formation and structure depend on the immediate environment of the bacteria. In the case of infection, the periprosthetic joint environment represents a particular interface between bacteria, host cells, and the implant, favoring biofilm initiation and maturation. Treating such an infection represents a huge challenge because of the biofilm-specific high tolerance to antibiotics and its ability to evade the immune system. It is crucial to understand these mechanisms in order to find new and adapted strategies to prevent and eradicate implant-associated infections. Therefore, adapted models mimicking the infectious site are of utmost importance to recreate a relevant environment in order to test potential antibiofilm molecules. In periprosthetic joint infections, Staphylococcus aureus is mainly involved because of its high adaptation to the human physiology. The current review deals with the mechanisms involved in the antibiotic resistance and tolerance of Staphylococcus aureus in the particular periprosthetic joint infection context, and exposes different strategies to manage these infections.

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

Cited by 108 publications

References 115 publications

IsdB antibody–mediated sepsis following S. aureus surgical site infection

IsdB antibody–mediated sepsis following S. aureus surgical site infection

Identification of Penicillin Binding Protein 4 (PBP4) as a critical factor for Staphylococcus aureus bone invasion during osteomyelitis in mice

Antibiotic Tolerance of Staphylococcus aureus Biofilm in Periprosthetic Joint Infections and Antibiofilm Strategies

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