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.