Involvement of mitogen-activated protein kinase pathways in Staphylococcus aureus invasion of normal osteoblasts

Area of Science:

• Cell Biology
• Microbiology
• Immunology

Background:

• Staphylococcus aureus is a common pathogen that invades osteoblasts, the cells responsible for bone formation.
• Intracellular persistence of S. aureus within osteoblasts contributes to chronic bone infections.
• The role of host cell signaling pathways, such as mitogen-activated protein kinases (MAPKs), in bacterial invasion is not fully understood.

Purpose of the Study:

• To investigate the involvement of osteoblast MAPK pathways in Staphylococcus aureus invasion.
• To determine which specific MAPK pathways are activated during S. aureus infection of osteoblasts.
• To elucidate the relationship between bacterial adherence, gene expression, and MAPK activation.

Main Methods:

• Infection of human and mouse osteoblasts with S. aureus.
• Measurement of MAPK pathway activation through phosphorylation assays (ERK 1/2, stress-activated protein kinases, p38 MAPK).
• Assessment of bacterial adherence and dependence on active bacterial gene expression.

Main Results:

• S. aureus infection significantly increased phosphorylation of extracellular signal-regulated kinases (ERK 1 and 2) in osteoblasts.
• ERK 1/2 activation correlated with the time course of bacterial invasion and was induced by bacterial adherence.
• While stress-activated protein kinases were upregulated, the p38 MAPK pathway was not activated; c-Jun was phosphorylated, but Elk-1 and ATF-2 were not.

Conclusions:

• Osteoblast ERK 1/2 and stress-activated protein kinase pathways are activated during S. aureus invasion.
• ERK 1/2 activation is dependent on bacterial adherence and active gene expression.
• These findings highlight specific host cell signaling pathways involved in S. aureus osteoblast pathogenesis.