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. 2021;12(3):201-211.
doi: 10.1007/s42485-021-00068-9. Epub 2021 Jul 16.

Prioritization of potential drug targets and antigenic vaccine candidates against Klebsiella aerogenes using the computational subtractive proteome-driven approach

Vijina Chakkyarath  1 , Anusuya Shanmugam  2 , Jeyakumar Natarajan  1
Affiliations

Prioritization of potential drug targets and antigenic vaccine candidates against Klebsiella aerogenes using the computational subtractive proteome-driven approach

Vijina Chakkyarath et al. J Proteins Proteom. 2021.

Abstract

Klebsiella aerogenes is a multidrug-resistant Gram-negative bacterium that causes nosocomial infections. The organism showed resistance to most of the conventional antibiotics available. Because of the high resistance of the species, the treatment of K. aerogenes is difficult. These species are resistant to third-generation cephalosporins due to the production of chromosomal beta-lactams with cephalosporin activity. The lack of better treatment and the development of therapeutic resistance in hospitals hinders better/new broad-spectrum-based treatment against this pathogen. This study identifies potential drug targets/vaccine candidates through a computational subtractive proteome-driven approach. This method is used to predict proteins that are not homologous to humans and human symbiotic intestinal flora. The resultant proteome of K. aerogenes was further searched for proteins, which are essential, virulent, and determinants of antibiotic/drug resistance. Subsequently, their druggability properties were also studied. The data set was reduced based on its presence in the pathogen-specific metabolic pathways. The subtractive proteome analysis predicted 13 proteins as potential drug targets for K. aerogenes. Furthermore, these target proteins were annotated based on their spectrum of activity, cellular localization, and antigenicity properties, which ensured that they are potent candidates for broad-spectrum antibiotic and vaccine design. The results open up new opportunities for designing and manufacturing powerful antigenic vaccines against K. aerogenes and the detection and release of new and active drugs against K. aerogenes without altering the gut microbiome.

Supplementary information: The online version contains supplementary material available at 10.1007/s42485-021-00068-9.

Keywords: Drug targets; Enterobacter/Klebsiella infections; Subtractive proteome analysis; Vaccine candidates.

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Conflict of interest statement

Conflict of interestThe authors declare that there is no conflict of interest.

Figures

Fig. 1
Fig. 1
Schematic representation of the workflow. The flowchart summarizes the various steps that were used to identify and characterize potential drug targets in the study
Fig. 2
Fig. 2
Pie-chart depicts the distribution of the 13 drug targets in unique metabolic pathways of K. aerogenes
See this image and copyright information in PMC

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