Introduction
Osteomyelitis is an inflammatory disease characterized by bacterial infection causing bone destruction and secondary bone proliferation. It can be caused by aerobic or anaerobic bacteria, branched bacteria, and fungi. Epidemiological studies have shown that Staphylococcus aureus is the most common and predominant pathogen causing osteomyelitis[1, 2]. Bone tissue is prone to chronic transformation and difficult to completely cure after infection with Staphylococcus aureus, leading to recurrent infections[3]. Studies have shown that Staphylococcus aureus forms a biofilm mainly on the pits of cortical bone or dead bone tubules after infecting bone tissue, and secretes a large amount of immune-regulatory proteins, toxins, and other virulence factors, causing immune cell death, complement activation disorders, and immune evasion of Staphylococcus aureus[4, 5]. Therefore, osteomyelitis caused by Staphylococcus aureus has a high recurrence rate, and remains a challenging medical problem in China and worldwide.
Staphylococcus aureus is a gram-positive pathogen widely present in the population, mainly found on the human skin and nasal cavity[6, 7]. The cell wall of Staphylococcus aureus is composed of 90% peptidoglycan and 10% wall teichoic acid, which gives it a strong ability to adapt to the environment and resist adverse factors[8-10]. It spreads widely in the population and causes a series of diseases in the human body, such as vascular, lower respiratory tract, soft tissue, and skin infections, endocarditis, and osteomyelitis[11]. It is well known that Staphylococcus aureus mainly infects the host through its surface recognition proteins, anchors itself to the host cell surface by mediating some adhesion mechanisms, releases toxins to induce host immune reactions, and ultimately infects the host[12, 13]. Studies have found that Staphylococcus aureus can express up to 24 cell wall-anchored proteins, which can be divided into the MSCRAMM family, G5-E repeat domain protein family, Three-Helical Bundles family, NEAT motif family, legume lectin domain protein family, nucleotidase motif, etc., based on their secondary structure characteristics[14, 15]. Among them, the MSCRAMM family mainly consists of proteins located on the surface of Staphylococcus aureus that can recognize and adhere to various host components[16]. It is crucial for the adhesion, invasion, and immune evasion mechanisms of the pathogen and as a member of the MSCRAMM family, SDRC protein’s biological effects are immeasurable[17, 18].
SDRC protein mainly plays a biological role by mediating the formation of Staphylococcus aureus biofilm[19]. BARBU E M et al. used a phage library to screen the interaction between amino acids 247-251 and 288-292 at the C-terminus of the N2 domain of SDRC protein and found that SDR protein can promote biofilm formation[19-21]. Meanwhile, inhibiting the interaction of SDRC protein itself inhibits biofilm formation, fully demonstrating the critical role of SDRC protein in Staphylococcus aureus infectious diseases.
In our study, we first knocked out the SDRC protein in the structure of Staphylococcus aureus in vitro, and explored the specific role of SDRC protein in osteomyelitis by constructing a mouse osteomyelitis model infected with Staphylococcus aureus. At the same time, we also combined transcriptome sequencing technology to further explore the specific mechanism by which the SDRC protein affects the progression of osteomyelitis, aiming to elevate the treatment of osteomyelitis to a new level.