Com1 as a Promising Protein for the Differential Diagnosis of the Two Forms of Q Fever

Abstract

Coxiella burnetii is the causative agent of acute and chronic Q fever in humans. Although the isolates studied so far showed a difference in virulence potential between those causing the two forms of the disease, implying a difference in their proteomic profile, the methods used so far to diagnose the two forms of the disease do not provide sufficient discriminatory capability, and human infections may be often misdiagnosed. The aim of the current study was to identify the outer membrane Com1 (CBU_1910) as a candidate protein for serodiagnostics of Q fever. The protein was cloned, expressed, purified, and used as an antigen in ELISA. The protein was then used for the screening of sera from patients suffering from chronic Q fever endocarditis, patients whose samples were negative for phase I immunoglobulin G (IgG), patients for whom at least one sample was positive for phase I IgG, and patients suffering from any kind of rheumatoid disease. Blood donors were used as the control group. Following statistical analysis, 92.4% (122/132) of the samples tested agreed with the negative clinical diagnosis, and 72.2% (26/36) agreed with the positive clinical diagnosis. Moreover, a significant correlation to the presence of the disease (p = 0.00) was calculated. The results support the idea that a Com1 antigen-based serodiagnostic test may be useful for differential diagnosis of chronic Q fever. Further studies are required to compare more immunogenic proteins of the bacterium against samples originating from patients suffering from different forms of the disease.

Evaluation of the Diagnostic Potential of Recombinant Coxiella burnetii Com1 in an ELISA for the Diagnosis of Q Fever in Sheep, Goats and Cattle

“…While commercial ELISAs use whole cell lysates offering a broad variety of antigens, the here developed recombinant ELISA is based on a single, well-defined antigen. However, the vast majority of Q fever true positive animals (83% in total) reacted to recombinant Com1 protein indicating its diagnostic value as already shown for mice and just recently for humans [ 48 , 55 , 61 , 62 , 63 ].…”

“…Com1 as a chaperon catalyzes the formation of disulfide bonds in extra cytoplasmic proteins [ 52 , 53 ]. It has recently repeatedly been shown that Com1 as an antigen in an ELISA with human sera can lead to acceptable performance of the test with specificities of about 90% [ 54 , 55 ].…”

In the Search of Potential Serodiagnostic Proteins to Discriminate Between Acute and Chronic Q Fever in Humans. Some Promising Outcomes

“…In general, CBU_1910 (Com1) has been described in the literature as a credible diagnostic marker, exposed on the surface of C. burnetii. Furthermore, this protein has been perfectly described by Vranakis et al (2019), as a very good marker for the differential diagnosis of the chronic form of Q fever. More specifically, an ELISA assay was used in their study in order to screen blood sera from patients suffering either from the chronic or the acute phase of the disease.…”

“…The results of the current work together with our results of the Com1 (Vranakis et al, 2019) may be considered as a first step for the production of a serodiagnostic test that will be able to correctly diagnose chronic Q fever.…”

“…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. Among them, two (CBU_0937 and CBU_0612) are predicted as outer membrane proteins, and two (CBU_1718 and CBU_0092) are predicted to be localized in the periplasm of C. burnetii (Supplementary Table 2).…”