Identification of immunodominant Bartonella bacilliformis proteins: a combined in-silico and serology approach

Schlüfter, Elif; Ventosilla, Palmira; Schultze, Tilman G.; Ballhorn, Wibke; Tsukayama Cisneros, Pablo; Kempf, Volkhard A. J.; Ugarte Gil, Cesar Augusto; Dichter, Alexander A.; Wenigmann, Anne; Latz, Andreas; Guerra Allison, Humberto

dc.contributor.author	Dichter, Alexander A.
dc.contributor.author	Schultze, Tilman G.
dc.contributor.author	Wenigmann, Anne
dc.contributor.author	Ballhorn, Wibke
dc.contributor.author	Latz, Andreas
dc.contributor.author	Schlüfter, Elif
dc.contributor.author	Ventosilla, Palmira
dc.contributor.author	Guerra Allison, Humberto
dc.contributor.author	Ugarte Gil, Cesar Augusto
dc.contributor.author	Tsukayama Cisneros, Pablo
dc.contributor.author	Kempf, Volkhard A. J.
dc.date.accessioned	2021-11-11T21:54:54Z
dc.date.available	2021-11-11T21:54:54Z
dc.date.issued	2021
dc.identifier.uri	https://hdl.handle.net/20.500.12866/10055
dc.description.abstract	Background Bartonella bacilliformis is the aetiological agent of Carrión’s disease, a biphasic and highly lethal illness formerly restricted to the South American Andes that is now spreading to adjacent areas. Reliable serodiagnostic approaches and vaccines are urgently needed. In this study, we aimed to identify immunodominant proteins of B bacilliformis and to establish novel and reliable serodiagnostic tools. Methods We used a reverse vaccinology approach in combination with an analysis of heterologous genomic expression libraries to identify immunodominant proteins, on the basis of the genome sequences of B bacilliformis strains KC583 and KC584. Antigens were screened with serum samples collected from Peruvian patients with B bacilliformis infections and from German healthy blood donors without history of travel to South America. We further analysed immunoreactive proteins of B bacilliformis with immunoblotting and line blots. We used selected target proteins to develop a diagnostic ELISA. To assess the performance of this ELISA, we did receiver operating characteristic analyses to assess the area under the curve, cutoff values, sensitivities, and specificities with 95% CIs. Findings We used serum samples obtained between Dec 23, 1990, and May 5, 2018, from 26 Peruvian patients with B bacilliformis infections and serum samples taken between Aug 28 and Aug 31, 2020, from 96 healthy German blood donors. 21 potentially immunodominant proteins were identified and recombinantly expressed, and their reactivity was assessed with immunoblotting and line blots. Of these 21 antigens, 14 were found to be immunoreactive. By using serum samples of Peruvian patients with Carrión’s disease and of healthy German blood donors, we identified three antigens (porin B, autotransporter E, and hypothetical protein B) as suitable immunodominant antigens, and we applied them in a diagnostic ELISA using two different antigen combinations (porin B plus autotransporter E and porin B plus autotransporter E plus hypothetical protein B). For the combination of porin B and autotransporter E, with optical density measured at 450 nm (OD450) cutoff value of 0·29, sensitivity was 80·8% (95% CI 60·7–93·5) and specificity was 94·8% (88·3–98·3) for all Peruvian patient samples. For a combination of porin B, autotransporter E, and hypothetical protein B, with an OD450 cutoff of 0·34, sensitivity was 76·9% (56·4–91·0) and specificity was 93·8% (86·9–97·7) for all Peruvian patient samples. Interpretation This novel ELISA could represent a useful serodiagnostic tool for future epidemiological studies of B bacilliformis in endemic areas. Additionally, the immunodominant antigens we have identified could provide a first basis for future vaccine development to prevent the highly lethal Carrión’s disease	en_US
dc.language.iso	eng
dc.publisher	Elsevier
dc.relation.ispartofseries	Lancet. Microbe
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.rights.uri	https://creativecommons.org/licenses/by-nc-nd/4.0/deed.es
dc.subject	Bartonella bacilliformis proteins	en_US
dc.subject	in-silico	en_US
dc.subject	serology approach	en_US
dc.title	Identification of immunodominant Bartonella bacilliformis proteins: a combined in-silico and serology approach	en_US
dc.type	info:eu-repo/semantics/article
dc.identifier.doi	https://doi.org/10.1016/S2666-5247(21)00184-1
dc.relation.issn	2666-5247