title: Continuous evaluation of changes in the serum proteome from early to late stages of sepsis caused by Klebsiella pneumoniae.
abstract: Serum protein profiles of patients with bacterial sepsis from the day of diagnosis until recovery/mortality were compared from early to late stages in response to severe sepsis using two dimensional electrophoresis. The proteins exhibiting changes during the course of sepsis (20‑28 day mortality) were selected and identified by matrix‑assisted laser desorption ionization‑time of flight‑tandem mass spectrometry. Among the proteins identified, haptoglobin (Hp), transthyretin (TTR), orosomucoid 1/α1 acid glycoprotein (ORM1), α1 antitrypsin (A1AT), serum amyloid A (SAA) and S100A9 exhibited differential expression patterns between survivors (S; n=6) and non‑survivors (NS; n=6), particularly during the early stages of sepsis. Expression factors (EFs), taken as the ratio between the NS and S during early stages, showed ratios of Hp, 0.39 (P≤0.012); TTR, 3.96 (P≤0.03); ORM1, 0.69 (P≤0.79); A1AT, 0.92 (P≤0.87) and SAA, 0.69 (P≤0.01). S100A9, an acute phase protein, exhibited an EF ratio of 1.68 (P≤0.004) during the end stages of sepsis. A delayed rise in levels was observed in Hp, A1AT, ORM1, S100A9 and SAA, whereas TTR levels increased during the early stages of sepsis in NS. Analysis of inflammatory responses in the early stages of sepsis revealed increased mRNA expression in leukocytes of interleukin (IL)‑6 (EF, 2.50), IL‑10 (EF, 1.70) and prepronociceptin (EF, 1.6), which is a precursor for nociceptin in NS compared with S, and higher Toll‑like receptor‑4 (EF, 0.30) levels in S compared with NS. Therefore, a weaker acute phase response in the early stages of sepsis in NS, combined with an inefficient inflammatory response, may contribute to sepsis mortality.
authors.affiliation: Department of Microbiology, Osmania University, Hyderabad, Telangana 500007, India.
authors.forename: Swathi
authors.initials: S
authors.lastname: Raju M
authors.affiliation: Molecular Diagnostics and Biomarkers Department of Laboratory Medicine Global Hospitals, Hyderabad, Telangana 500004, India.
authors.forename: Jahnavi
authors.initials: J
authors.lastname: V
authors.affiliation: Molecular Diagnostics and Biomarkers Department of Laboratory Medicine Global Hospitals, Hyderabad, Telangana 500004, India.
authors.forename: Ratnakar S
authors.initials: RS
authors.lastname: Kamaraju
authors.affiliation: Molecular Diagnostics and Biomarkers Department of Laboratory Medicine Global Hospitals, Hyderabad, Telangana 500004, India.
authors.forename: Venkataraman
authors.initials: V
authors.lastname: Sritharan
authors.affiliation: Department of Microbiology, Osmania University, Hyderabad, Telangana 500007, India.
authors.forename: Karthik
authors.initials: K
authors.lastname: Rajkumar
authors.affiliation: Department of Biochemistry, Osmania University, Hyderabad, Telangana 500007, India.
authors.forename: Sumathi
authors.initials: S
authors.lastname: Natarajan
authors.affiliation: Department of Biochemistry, Osmania University, Hyderabad, Telangana 500007, India.
authors.forename: Anil D
authors.initials: AD
authors.lastname: Kumar
authors.affiliation: Department of Microbiology, Osmania University, Hyderabad, Telangana 500007, India.
authors.forename: Sandeepta
authors.initials: S
authors.lastname: Burgula
mesh_terms: D000368:Aged; D001798:Blood Proteins; D020869:Gene Expression Profiling; D006801:Humans; D007710:Klebsiella Infections / Q000097:blood* / Q000175:diagnosis / Q000382:microbiology; D007711:Klebsiella pneumoniae; D008297:Male; D008875:Middle Aged; D025941:Protein Interaction Mapping; D060066:Protein Interaction Maps; D020543:Proteome; D040901:Proteomics / Q000379:methods; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis / Q000382:microbiology / Q000401:mortality; D059467:Transcriptome
chemical_list: D001798:Blood Proteins; D020543:Proteome