Staphylococcus Aureus Infection And Acute Hematogenous Osteomyelitis In Children

Osteomyelitis(OM)is a severe inflammatory process of bone and bone marrow.Staphylococcus aureus(S.aureus)is the most common pathogen of OM.Acute hematogenous osteomyelitis(AHO)is mainly seen in prepubertal children.The host-pathogen interaction may affect the occurrence and development of OM.The host's blood transcriptional characteristics can distinguish different infectious diseases.However,the characteristics of the whole blood transcription profiles of S,aureus infection(SI)and OM remain unclear.By analyzing the characteristics of clinical information and whole blood transcription profiles of SI and OM,it is possible to improve the understanding of OM,especially AHO in children,and guide clinical practice.Chapter 1 Clinical characteristics of Staphylococcus aureus infection and osteomyelitisObjective:To analyze the clinical characteristics of SI and OM.Methods:Dataset GSE30119 was downloaded from the GEO database.The research objects were divided into two groups,healthy control group(Ctrl)and S.aureus infection group(SI).The infected children were subdivided into OM-free group(OFI)and OM group(OMI).Multiple comparisons between groups were performed.Observed indexes include demographic characteristics,clinical manifestations,hospitalization status,laboratory tests,isolation of S.aureus strains,and antibiotic treatment.Results:In terms of age,the OMI group was slightly older than the Ctrl group(p=0.037)and the OFI group(p=0.002).In terms of ethnicity,the rate of OM(OMI/SI)decreases in the order of Caucasian(17/24),African-American(24/38),Hispanic(13/30),and Other(3/7).There was no difference in gender between groups.Skin and soft tissue abscess,cellulitis,and bacteremia were common diseases in the top 5 disease spectrum of the OFI group and the OMI group.Bacteremia,myositis and septic arthritis may be more relevant to the pathogenesis of OM.The location of the infection and the severity of the disease may be positively related to the onset of OM.The hospitalization status of the OMI group was more complicated than that of the OFI group.The inflammatory indexs of the SI group were significantly higher than that in the control group,of which,only index ESR was significantly higher in the OMI group than the OFI group.68.69%of the SI group were infected with MRSA.The typing,clones,and virulence genes of all isolates were not significantly different between infected groups.Antibiotics were dominated by single drugs(76.77%),mainly clindamycin(40.4%)and cephalexin(17.17%).The combination of the two drugs is mainly represented by the combination of vancomycin,clindamycin,and rifampicin.Conclusion:SI and OM have unique clinical characteristics,respectively.Chapter 2 Whole blood transcriptional characteristics of Staphylococcus aureus infection and osteomyelitisObjective:To analyze the characteristics of whole blood transcriptional profiles of SI and OM,and to explore candidate genes and pathways.Methods:The grouped GSE30119 raw data were compared between groups and screened for the S.aureus infection-related genes(SARGs)and OM-related genes(OMRGs).GO terms and pathway enrichment analysis were performed on these differentially expressed genes(DEGs),followed by PPI network construction and module analysis.Results:A total of 785 DEGs were screened,of which 376 were up-regulated and 409 were down-regulated.209 SARGs and 377 OMRGs were identified.SARGs are mainly involved in regulating the immune response process.Among them,the formation of neutrophil extracellular traps(NETs)may be crucial for the immune response of SI.However,OMRGs are mainly enriched in transmembrane signal receptor and calcium channel activity,as well as cilia morphogenesis,chromosome silencing,and multicellular organ development.Several proteins,including PHLPP2 and EGF,are hub proteins in the PPI network of OMRGs.In addition,alcoholism,systemic lupus erythematosus,and proteoglycans in tumors may be related to the pathogenesis of osteomyelitis.Conclusion:Our study may light the further insight into the underlying molecular mechanisms and the potential critical biomarkers in OM development.