Distinct expression trend of signature antigens of Staphylococcus aureus osteomyelitis correlated with clinical outcomes

The major limitations of clinical outcome predictions of osteomyelitis mediated by Staphylococcus aureus (S. aureus) are not specific and definitive. To this end, current studies aim to investigate host immune responses of trend changes of the iron‐regulated surface determinant (Isd) of IsdA, IsdB, IsdH, cell wall‐modifying proteins of amidase (Amd) and glucosaminidase (Gmd), and secreted virulence factor of chemotaxis inhibitory protein S. aureus (CHIPS) and staphylococcal complement inhibitor (SCIN) longitudinally to discover their correlationship with clinical outcomes. A total of 55 patients with confirmed S. aureus infection of the long bone by clinical and laboratory methods were recruited for the study. Whole blood was collected at 0, 6, 12 months for the serum that was used to test IsdA, IsdB, IsdH, Gmd, Amd, CHIPS, and SCIN using a customized Luminex assay after clinical standard care parameters were collected. The patients were then divided into two groups: (1) infection controlled versus (2) adverse outcome based on clinical criteria for statistical analysis. We found that standard clinical parameters were unable to distinguish therapeutic outcomes. Significant overexpression of all antigens was confirmed in infection patients at 0‐, 6‐, and 12‐month time points. A distinct expression trend and dynamic changes of IsdB, Amd, Gmd, and CHIPS were observed between infection controlled and adverse outcome patients, while the IsdA, IsdH, SCIN remained demonstrated no statistical significance. We conclude that dynamic changes of specific antigens could predict clinical outcomes of S. aureus osteomyelitis. Clinical Relevance: The trend changes of host immune responses to S. aureus specific antigens of IsdB, Gmd, Amd, and CHIPS could predict clinical outcomes of S. aureus osteomyelitis.

[1]  C. Beck,et al.  Lack of Humoral Immunity Against Glucosaminidase Is Associated with Postoperative Complications in Staphylococcus aureus Osteomyelitis. , 2020, The Journal of bone and joint surgery. American volume.

[2]  C. Fekete,et al.  Characterization of methicillin-resistant Staphylococcus aureus through genomics approach , 2020, 3 Biotech.

[3]  Ronan K. Carroll,et al.  Reading between the Lines: Utilizing RNA-Seq Data for Global Analysis of sRNAs in Staphylococcus aureus , 2020, mSphere.

[4]  R. Buckley,et al.  The AO trauma CPP bone infection registry: Epidemiology and outcomes of Staphylococcus aureus bone infection , 2020, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[5]  C. Beck,et al.  Deriving a dose and regimen for anti-glucosaminidase antibody passive-immunisation for patients with Staphylococcus aureus osteomyelitis. , 2020, European cells & materials.

[6]  S. Kates,et al.  Development and challenges in setting up an international bone infection registry , 2019, Archives of Orthopaedic and Trauma Surgery.

[7]  W. Obremskey,et al.  Recommendations for Systemic Antimicrobial Therapy in Fracture-Related Infection: A Consensus From an International Expert Group , 2019, Journal of orthopaedic trauma.

[8]  S. Gill,et al.  Evolving concepts in bone infection: redefining “biofilm”, “acute vs. chronic osteomyelitis”, “the immune proteome” and “local antibiotic therapy” , 2019, Bone Research.

[9]  Fu-Der Wang,et al.  Distribution of virulence genes in bacteremic methicillin-resistant Staphylococcus aureus isolates from various sources. , 2019, Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi.

[10]  S. Gill,et al.  Tracking Anti-Staphylococcus aureus Antibodies Produced In Vivo and Ex Vivo during Foot Salvage Therapy for Diabetic Foot Infections Reveals Prognostic Insights and Evidence of Diversified Humoral Immunity , 2018, Infection and Immunity.

[11]  C. Jo,et al.  Seasonal Variation and Weather Changes Related to the Occurrence and Severity of Acute Hematogenous Osteomyelitis in Children , 2018, Journal of the Pediatric Infectious Diseases Society.

[12]  S. Yoon,et al.  Disruption of the Gut Ecosystem by Antibiotics , 2017, Yonsei medical journal.

[13]  R. G. Richards,et al.  Fracture-related infection: A consensus on definition from an international expert group. , 2017, Injury.

[14]  S. Kates,et al.  Epidemiological, Clinical and Microbiological Characteristics of Patients with Post-Traumatic Osteomyelitis of Limb Fractures in Southwest China: A Hospital-Based Study , 2017, Journal of bone and joint infection.

[15]  H. Gregersen,et al.  Chinese health care system and clinical epidemiology , 2017, Clinical epidemiology.

[16]  R. G. Richards,et al.  Orthopaedic device-related infection: current and future interventions for improved prevention and treatment , 2016, EFORT open reviews.

[17]  S. Kates,et al.  Regional characteristics of postoperative bacterial infection and antibiotic resistance following traumatic limb fractures , 2016 .

[18]  C. Beck,et al.  A Diagnostic Serum Antibody Test for Patients With Staphylococcus aureus Osteomyelitis , 2015, Clinical orthopaedics and related research.

[19]  R. Sampath,et al.  PCR-Electrospray Ionization Mass Spectrometry for Direct Detection of Pathogens and Antimicrobial Resistance from Heart Valves in Patients with Infective Endocarditis , 2013, Journal of Clinical Microbiology.

[20]  C. Malone,et al.  Alpha-Toxin Induces Programmed Cell Death of Human T cells, B cells, and Monocytes during USA300 Infection , 2012, PloS one.

[21]  J. Parvizi,et al.  New Definition for Periprosthetic Joint Infection: From the Workgroup of the Musculoskeletal Infection Society , 2011, Clinical orthopaedics and related research.

[22]  J. V. van Dijl,et al.  A multiplex assay for the quantification of antibody responses in Staphylococcus aureus infections in mice. , 2011, Journal of immunological methods.

[23]  A. van Belkum,et al.  Heterogeneity of the humoral immune response following Staphylococcus aureus bacteremia , 2010, European Journal of Clinical Microbiology & Infectious Diseases.

[24]  W. Sewell,et al.  Clinical uses of intravenous immunoglobulin , 2005, Clinical and experimental immunology.

[25]  B. Kocsis,et al.  Comparison of Antibody Repertoires against Staphylococcus aureus in Healthy Individuals and in Acutely Infected Patients , 2005, Clinical Diagnostic Laboratory Immunology.

[26]  T. Foster The Staphylococcus aureus "superbug". , 2004, The Journal of clinical investigation.

[27]  E. Regan,et al.  Orthopaedics in the Buddhist kingdom of Bhutan. , 2002, Clinical orthopaedics and related research.

[28]  R. Zagursky,et al.  Transcription Profiling-Based Identification ofStaphylococcus aureus Genes Regulated by the agrand/or sarA Loci , 2001, Journal of bacteriology.

[29]  G. Calandra,et al.  Evaluation of new anti-infective drugs for the treatment of osteomyelitis in adults. Infectious Diseases Society of America and the Food and Drug Administration. , 1992, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.