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Identification of miRNA Biomarkers Associated With Staphylococcal Musculoskeletal Infections
Claudia Siverino1, Eric Sumrall1, Jorge Úbeda Garrido1
1AO Research Institute Davos, Davos Platz, Switzerland.
Abstract:
Musculoskeletal infections (MSKIs) pose significant challenges in orthopedic surgery. These infections are often caused by Staphylococcus aureus and S. epidermidis. Early diagnosis is crucial, as it allows prompt treatment before the infection becomes chronic and more difficult to manage. This study evaluated the expression of microRNAs (miRNAs) in the serum of patients with staphylococcal MSKI and their potential as biomarkers. Serum samples from patients with confirmed staphylococcal MSKI were used for RNA sequencing and validation (n = 24 S. aureus, n = 25 S. epidermidis and n = 25 controls). In S. aureus-infected patients compared to uninfected controls, 23 miRNAs were upregulated and 20 downregulated, while 94 miRNAs were upregulated and 31 downregulated in those infected with S. epidermidis. Validation experiments revealed the upregulation of hsa-miR-1246, hsa-miR-483-5p, and hsa-miR-1290, and the downregulation of hsa-miR-1-3p, hsa-miR-148b-3p, and hsa-miR-23a-3p in S. aureus-infected patients compared to both S. epidermidis-infected patients and uninfected controls. Human peripheral blood mononuclear cells treated in vitro with bacterial culture supernatants exhibited a similar pattern of miRNA expression. Receiver operating characteristic (ROC) curve analyses demonstrated that combining four miRNAs (miR-1246, miR-1290, miR-148b-3p, and miR-23a-3p) achieved a high diagnostic accuracy, with an area under the curve of 0.96, distinguishing S. aureus from S. epidermidis-infected patients. In summary, this study identified four differentially expressed miRNAs in S. aureus-infected patients compared to those with S. epidermidis infections and uninfected controls. These findings allow miRNA to be used as MSKI markers and to study their effect on immune responses during bacterial infections.
Insights
This study identifies four microRNAs (miRNAs) as potential biomarkers for diagnosing Staphylococcus aureus musculoskeletal infections (MSKIs). These specific miRNAs can help differentiate S. aureus from S. epidermidis infections, aiding orthopedic surgery.
Area of Science:
- Orthopedic Surgery
- Infectious Diseases
- Molecular Biology
- Biomarker Discovery
Background:
- Musculoskeletal infections (MSKIs) present significant challenges in orthopedic surgery, often caused by Staphylococcus aureus and S. epidermidis.
- Early diagnosis is critical for effective treatment and preventing chronic infection.
- MicroRNAs (miRNAs) are emerging as potential diagnostic biomarkers for various conditions.
Purpose of the Study:
- To evaluate serum miRNA expression in patients with staphylococcal MSKIs.
- To identify specific miRNAs that can serve as diagnostic biomarkers for differentiating S. aureus from S. epidermidis infections.
- To explore the role of these miRNAs in the immune response to bacterial infections.
Main Methods:
- Serum samples were collected from patients with confirmed S. aureus MSKI, S. epidermidis MSKI, and healthy controls.
- RNA sequencing was performed to analyze miRNA expression profiles.
- Validation of differentially expressed miRNAs was conducted using quantitative real-time PCR.
- Receiver operating characteristic (ROC) curve analysis was used to assess diagnostic accuracy.
Main Results:
- Significant differences in miRNA expression were observed between S. aureus, S. epidermidis, and control groups.
- Specific miRNAs (hsa-miR-1246, hsa-miR-483-5p, hsa-miR-1290, hsa-miR-1-3p, hsa-miR-148b-3p, hsa-miR-23a-3p) were identified as differentially expressed.
- A panel of four miRNAs (miR-1246, miR-1290, miR-148b-3p, and miR-23a-3p) demonstrated high diagnostic accuracy (AUC=0.96) in distinguishing S. aureus from S. epidermidis infections.
Conclusions:
- This study identified a panel of four miRNAs with potential as diagnostic biomarkers for S. aureus MSKIs.
- These miRNAs can aid in differentiating between S. aureus and S. epidermidis infections, improving orthopedic surgical outcomes.
- Further research into the immunomodulatory roles of these miRNAs in bacterial infections is warranted.
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