Abstract

Coxiella burnetii is the agent that causes acute and chronic Q fever infections in humans. Although the isolates studied so far have shown that the two forms of the disease differ in virulence potential thus, implying a variance in their proteomic profile, the methods used do not deliver enough discriminatory capability and often, human infections may be mis-diagnosed. The current study adds further knowledge to the results that we have already published on the Coxiella outer membrane protein 1 (Com1). Herein we identified the proteins GroEL, Ybgf, OmpH, and UPF0422 as candidates for serodiagnostics of Q fever; following cloning, expression and purification they were further used as antigens in ELISA for the screening of patients' sera associated with chronic Q fever endocarditis, sera negative for phase I IgG, sera with at least one sample positive for phase I IgG and sera from patients who suffered from various rheumatic diseases. Blood donors were used as the controls. Sensitivity, specificity, positive predictive value, negative predictive value, and Cohen's kappa coefficient (κ) were calculated and we also performed binary logistic regression analysis to identify combinations of proteins with increased diagnostic yield. We found that proteins GroEL and Ybgf, together with Com1, play the most significant role in the correct diagnosis of chronic Q fever. Of these three proteins, it was shown that Com1 and GroEL present the highest sensitivity and specificity altogether. The results add to the existing knowledge that an antigen-based serodiagnostic test that will be able to correctly diagnose chronic Q fever may not be far from reality.

Highlights

  • Coxiella burnetii, the aetiological agent of Q fever, is a small intracellular Gram-negative bacterial pathogen that since 2009 has been shown that may survive outside an intracellular nature of parasitism (Omsland et al, 2009)

  • We have identified and determined antigenic proteins which could be used for the development of a chronic Q fever specific ELISA

  • Continuing our earlier work (Vranakis et al, 2019), in the current study four proteins were selected for validation of their antigenic properties with respect to their capacity to differentiate the chronic from acute infections of Q fever

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Summary

Introduction

The aetiological agent of Q fever, is a small intracellular Gram-negative bacterial pathogen that since 2009 has been shown that may survive outside an intracellular nature of parasitism (Omsland et al, 2009). The pathogen displays antigenic variations which are related to the mutational variation in its lipopolysaccharide (LPS) (Maurin and Raoult, 1999). Bacteria in phase I stage (natural phase corresponding to smooth LPS), are detected in humans and animals and are characterized of high infectivity (Maurin and Raoult, 1999). The characteristics of C. burnetii such as environmental stability, extremely low infectious dose (Moos and Hackstadt, 1987; Hackstadt, 1996) and aerosol route of exposure have classified the bacterium as a category B agent for bioterrorism (Oyston and Davies, 2011)

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