About this Research Topic

Background

Bacterial bone and joint infections (BJI) remain among the most challenging and difficult-to-treat complications of musculoskeletal trauma or orthopedic surgery. These infections range from implant-associated infections such as peri-prosthetic joint infection, fracture-related infection, instrumented spinal infections; to native skeletal infections such as acute hematogenous osteomyelitis, diabetic foot infection, septic arthritis, and vertebral osteomyelitis. Bone and joint infections can be a challenge to treat, with the need for extensive bone resection and prolonged antibiotic therapy. Even with appropriate treatment, patients suffering from BJI often experience infection-associated complications and unacceptably high recurrence rates.

The Staphylococcus genus causes up to two-thirds of all bone and joint infections, with Staphylococcus aureus the most frequently isolated pathogen, and a significant portion of staphylococcal isolates being methicillin-resistant. Research into host-pathogen interactions has revealed several factors that have enabled S. aureus to become the predominant pathogen in bone and joint infection. Through surface adhesins, it can bind and colonize bone and other exposed proteinaceous surfaces; it can invade and propagate through the osteocyte lacuno-canalicular network; it can form biofilms on any orthopedic device and on necrotic bone; and it can survive within abscess communities despite the accumulation of host defense cells. This is in addition to the numerous other virulence factors supporting infection in other tissues such as toxin secretion, immune evasion, and persister cell formation that further support the establishment of infection and protect from host and antibiotic attack.

An improved understanding of the fundamental biological processes underlying bone and joint infections should serve to identify new treatment and diagnostic modalities that have been rather limited in recent decades. With this Research Topic, we welcome researchers to contribute basic and translational research articles on the rapidly evolving field of staphylococcal skeletal infections. The primary focus areas include understanding host-pathogen interactions and immune responses (innate and adaptive) during staphylococcal bone and joint infections. In addition, developing diagnostic and prognostic tools for reliably identifying and monitoring these infections is an important focus area.

We welcome the submission of reviews, mini reviews, opinions, perspectives, and novel primary research articles in the aforementioned focus areas. In particular, we seek articles that cover the following subtopics:
• Staphylococcal adaptation to bone during BJI, including genomic, proteomic, or transcriptomic investigations;
• Emerging therapeutics in preclinical or clinical stage targeting BJI, including passive or active vaccines, bone-targeted antibiotics, bacteriophages or endolysins, dual antibiotic, osteoconductive biomaterials for tissue regeneration after BJI, augmentation of osteoclastogenic signaling or activity;
• The interplay between gut microbiota and BJI;
• The role of cytokines in modulating host responses during BJI;
• The role of skeletal cell pattern recognition receptors in the pathogenesis of osteomyelitis;
• Novel immunodiagnostic approaches utilizing humoral antibody and cell mediated (cytokines) responses;
• The role of comorbidities in the incidence or progression of bone and joint infections (e.g., diabetes, obesity, etc.); and
• Novel models of BJI that incorporate human cells, tissues, or humanized mice.

Keywords: Host-Pathogen Interactions, Staphylococcal Infections, Immunodiagnostics, Bone Infections, Staphylococcus aureus

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