In silico identification of drug targets and vaccine candidates against Bartonella quintana: a subtractive proteomics approach

Abstract

Background: The availability of genes and protein sequences for parasites has provided valuable information for drug target identification and vaccine development. One such parasite is Bartonella quintana, a Gram-negative, intracellular pathogen that causes bartonellosis in mammalian hosts.

Objective: Despite progress in understanding its pathogenesis, limited knowledge exists about the virulence factors and regulatory mechanisms specific to B. quintana.

Methods and findings: To explore these aspects, we have adopted a subtractive proteomics approach to analyse the proteome of B. quintana. By subtractive proteins between the host and parasite proteome, a set of proteins that are likely unique to the parasite but absent in the host were identified. This analysis revealed that out of the 1197 protein sequences of the parasite, 660 proteins are non-homologous to the human host. Further analysis using the Database of Essential Genes predicted 159 essential proteins, with 28 of these being unique to the pathogen and predicted as potential putative targets. Subcellular localisation of the predicted targets revealed 13 cytoplasmic, eight membranes, one periplasmic, and multiple location proteins. The three-dimensional structure and B cell epitopes of the six membrane antigenic protein were predicted. Four B cell epitopes in KdtA and mraY proteins, three in lpxB and BQ09550, whereas the ftsl and yidC proteins were located with eleven and six B cell epitopes, respectively.

Mains conclusions: This insight prioritises such proteins as novel putative targets for further investigations on their potential as drug and vaccine candidates.

Fig. 1:. stepwise analysis flowchart for the subtractive proteomics analysis of Bartonella quintana. The green colour box consists of the pathogen name (B. quintana str. Toulouse), which is the starting step of the analysis. The grey colour box represents the methodological aspects at each analysis step. The gold colour box represents the homologous and non-essential data and is discarded. The light blue colour box represents the essential non-homologous and therapeutic targets.

Fig. 2:. distribution of non-homologous essential therapeutic targets. (A) Unique essential proteins are present in each unique metabolic pathway; (B) Subcellular localisation of therapeutic target proteins show the majority are cytoplasmic.

Fig. 3:. the discontinuous B cell epitope predicted using ElliPro. The coloured sphere shows the B cell epitope. The sphere is coloured according to the order of the PyMOL colour code Red > Green > Blue > Yellow > Magenta > Cyan. Red colours show the highest score of epitopes from A to F at the top of the figure. Similarity: discontinuous B cell epitopes predicted using DiscoTope are shown as brown from G to L at the bottom of the figure.