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Table 3 Proteomic approaches for C. burnetii biomarker selection

From: Proteomics paves the way for Q fever diagnostics

Approach Technique(s) Cbisolates (culture method*) Sera/mAbs Applications Identified proteins Reference(s)
Biotyping       
Detection of specific markers for Cb isolates MALDI-TOF MS Cb: RSA493, BUD, Priscilla (CYSEE) - Optimization of method for typing Cb for specific strains or clinical isolates RSA493-specific: CBU_1637, CBU_0401, CBU_0394, CBU_1592, CBU_1378, CBU_0403, CBU_0078, CBU_0961, CBU_1698, CBU_0644, CBU_1055 Priscilla-specific: CBU_0149, CBU_0438, CBU_0168, CBU_0745 BUD-specific: CBU_1989, CBU_2085 [20, 54]
Identification of Cb strains and isolates MALDI-TOF MS Cb: NMI, Australian QD, M44, KAV, PAV, Henzerling, Ohio (CYSEE) - Cb isolate typing or diagnosis Mass spectral peaks (1000-6000 Da), species-selective and strain-specific [55]
Proteome of Cb NM I 2-DE and nanoLC-ESI MS/MS, LC-MALDI TOF/TOF MS, MALDI-TOF MS TPE Cb RSA493, NM I (CC) - Markers of early stage infection, and therapeutic or vaccine development 197 distinct proteins. Vir and Strep: CBU_0691, CBU_0683 SP: CBU_0091, CBU_0109, CBU_0395, CBU_0867, CBU_1221, CBU_1268, CBU_1718, CBU_1910 [19]
In silico prediction of OMPs and identification of Cb (NM I) LP Bioinformatics Cb RSA493 genome sequence - Vaccine development or serodiagnosis 21 predicted OMPs and 9 LP; LP: CBU_1190 (LolA), CBU_1829 (LolB) [59]
Proteome of Cb strain NM phase II 2-DE, 2D SDS-tricine PAGE, MALDI-TOF TPE Cb NM II (CC, Vero) - Markers of active Cb infection, serology or therapeutic development Proteins involved in Cb pathogenesis and survival mechanisms (NM II) [94]
Proteome of Cb I and II LC-MS/MS Cb NM I and II (CYSEE) - Phase I and phase II distinct biomarkers, serology or biotyping (blood transfusion) 150 proteins reported (pI > 9. 5); virulence type I and T4SS: CBU_0884, CBU_0085, CBU_0318, CBU_0744, CBU_1099, CBU_1352, CBU_0338, DotD protein (CBU_1643); Anks: CBU_0898, CBU_1482; 7 enzymes involved in LPS phase I synthesis: CBU_0676, CBU_0678, CBU_0674, CBU_0681, CBU_0682, CBU_0683, CBU_0691, CBU_0846, CBU_1657 [17]
Cb secretome Tricine-SDS PAGE, ESI-MS/MS, bioinformatics Cb NM II (CC, Vero) Cytoplasmic fraction from infected Vero cells Characterization of T4SS, drug development 50 T4SS effector candidates: CBU_1440, CBU_0312, CBU_1091, CBU_1386, CBU_1518, Orf145, QpH1_p21, CBU_1297, CburD_01001397 [33]
Two Cb strains, subproteome (OMPs) and candidate proteins for serodiagnosis Tris-Tricine SDS-PAGE, doubled SDS-PAGE, IP 2-DE, MALDI TOF/TOF Cb strains NM RSA 493 II (acute) and CbuG_Q212 II (chronic), (CC, Vero) OMP-enriched fraction, 1 HS (chronic) Subproteome of Cb, chronic Q fever markers 86 identified OMPs. SP: htpB, CBU_0236, CBU_0263, CBU_1471, CBU_0572, CBU_0235, CBU_1916, CBU_0612, CBU_0937 [56]
Immunoproteomics or serology     
Candidate proteins for acute Q fever serodiagnosis IP/serodiagnosis 17 Cb strains (CC) (BGM or L929) RP ada (rada), AS immunized with rada Marker of acute Q fever adaA (CBU_0952) [31, 63]
Identification of Cb cell-variant-specific common SCV/LCV proteins IP (2-DE, MALDI-TOF) Purified SCVs and LCVs HS (convalescent-phase, acute Q fever), AS from infected or vaccinated guinea pigs Subunit vaccines or serodiagnostics for acute Q fever, unique SCV/LCV markers Proteins that are differentially expressed in SCV and LCV forms. SP: CBU_1718, CBU_0236, CBU_0229, CBU_1943, CBU_1416, CBU_0952, CBU_0963, CBU_0737, CBU_0497, CBU_1200 [31]
SP for serodiagnosis of Q fever endocarditis IP (2-DE/MALDI-TOF) TPE Cb NM II (CC, Vero) HS (acute Q fever or IE Q fever) Markers of chronic Q fever (IE), serodiagnosis CBU_0612, CBU_0480 [57]
Identification of Cb proteins reacting with Cb mAbs IP (2-DE/MALDI-TOF) RP-based ELISA TPE Cb NM II (CC, Vero) Specific mAbs; HS acute or chronic (IE) Markers of chronic Q fever (IE), serodiagnosis Q fever markers (general): CBU_1910, CBU_0236 Chronic Q fever marker (IE): CBU_0937 [58]
SP for early serodiagnosis of Q fever IP (2-DE, LC-MS/MS) (pH 5-8, pH 3-10; phase I and phase II antigens ) TPE Cb NM I and II (CC, L929), Cb NM RSA493 I (CYSEE) AS from immunized guinea pigs Markers of early stage acute Q fever, serodiagnosis or vaccine development Phase-I-specific SP: CBU_1706, CBU_12190, CBU_0495, CBU_0780, CBU_0955, Phase-II-specific SP: CBU_1290, CBU_0235, CBU_0215, CBU_0572, CBU_1398, CBU_0236, CBU_0092, CBU_1241, CBU_1396, CBU_1227, CBU_0481, CBU_0299, CBU_0481, CBU_0495, CBU_0482, CBU_0937, CBU_0236 [68]
RP-based approaches      
Candidate RPs for Q fever vaccine development and serodiagnosis TAP products and expression of selected SP   HS (acute, chronic phase vaccine) Serodiagnosis or vaccine development SP: CBU_0008, CBU_0381, CBU_0612, CBU_0781, CBU_1115, CBU_1143, CBU_1157, CBU_1249, CBU_1853, CBU_1869 Top candidates: CBU_0781 (AnkG), CBU_1115 (lipoprotein), CBU_1143 (YajC) [66]
Candidate RPs for Q fever vaccine development and serodiagnosis Protein microarray   HS Q fever (general) Markers of Q fever (general) SP: CBU_1910, CBU_0891, CBU_0109, CBU_1143, CBU_0612, CBU_0092, CBU_0545, CBU_1398, CBU_0630, CBU_1513, CBU_1719, CBU_0229, CBU_0653 [69]
Candidate RPs for Q fever vaccine development and serodiagnosis ELISA (HS), ELISPOT (AS) 11 RPs, Cb NM RSA493 I HS Q-fever (IFA-positive, convalescent), HS chronic (transgenic mice, immunized with Cb NM RSA493 I) Subunit vaccine development, serodiagnosis SP: CBU_1910, CBU_1716, CBU_612, CBU_718, CBU_311 [67]
Identification of Cb SP IP (2D, LC-MS), tripartite fusion RP TPE Cb (I and II Henzerling strain) (CC, Vero) HS Q fever (general) Serodiagnosis or vaccine development SP: CBU_0091, CBU_0109, CBU_0395, CBU_0867, CBU_1221, CBU_1268, CBU_1718, CBU_1910 Six RP(Cb II): GroEL, Com1, RecA, EF-Tu, OmpA-like and FtsZ [65]
  1. I, phase I; II, phase II; adaA, acute disease antigen A; AS, animal sera; Cb, Coxiella burnetii; IE, infective endocarditis; HS, human sera; IP, immunoproteomics; LP, lipoproteins; MAb, monoclonal antibody; MW, molecular weight; nanoLC-ESI MS/MS, nano liquid chromatography-electrospray ionization mass spectrometry; NM, Nine Mile; OM, outer membrane; OMP, outer membrane protein; RP, recombinant protein; SP, seroreactive proteins; TAP products, transcriptionally active PCR products, TPE, total protein extract; Vir and Strep: synthesis of virenose and streptose.
  2. *CYSEE, cultured on yolk sacs in embryonated eggs; CC, cultured in cell lines.