Research Article
In silico identification of vaccine candidates against Klebsiella oxytoca

https://doi.org/10.1016/j.compbiolchem.2017.05.003Get rights and content

Highlights

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    Potential vaccine candidates against Klebsiella Oxytoca have been identified.

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    A Reverse Vaccinology approach has been adopted.

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    By using extensive computational tools the problems of conventional Vaccine production has been reduced.

Abstract

Klebsiella oxytoca causes several diseases in immunocompromised as well as healthy individuals. Increasing resistance to a number of antibiotics makes treatment options limited. Prevention using vaccine could be an important solution to get rid of infections caused by Klebsiella oxytoca. In recent time, genome based approaches have contributed significantly in vaccine development. Our aim was to identify the most conserved and immunogenic antigens that can be considered as potential vaccine candidates. KEGG database was used to find out pathways unique to the bacteria. Subcellular localization of the protein sequences taken from the selected 36 pathways were predicted using PSORTb v3.0.2 and CELLO v2.5. Prediction of B cell epitope and the probability of the antigenicity were evaluated by using IEDB and Vaxijen respectively. BLASTp was done to find out the similarity of the selected proteins with the human proteome. Proteins failing to comply with the set parameters were filtered at each step. Finally, we identified 6 surface exposed proteins as potential vaccine candidates against Klebsiella oxytoca.

Introduction

Klebsiella oxytoca is a gram-negative, rod shaped, non- motile bacterium belonging to the family Enterobacteriaceae (Gorkiewicz, 2009). It is an opportunistic pathogen that causes nosocomial infections in hospitalized patients, including children and neonates (Podschun and Ullmann, 1998).It has now been established that Klebsiella is the second most frequent causative agent of gram-negative bacteremia after E. coli (Yinnon et al., 1996) and Klebsiella oxytoca is the second most frequent cause of bacteremia after Klebsiella pneumonia (Lin et al., 1997). Klebsiella oxytoca is also causative agent of antibiotic-associated hemorrhagic colitis (AAHC) (Hoffmann et al., 2010). The organism is capable of overcoming the innate immune defence. It has numbers of virulence factors such as adhesins, siderophores, capsular polysaccharides (CPLs) and cell surface lipopolysaccharides (LPSs). K antigen of the capsule plays an important role in pathogenicity (Smit et al., 1986). Although lipopolysaccharides (LPS) are able to activate complement but the capsular polysaccharide of Klebsiella covers the LPS (Podschun and Ullmann, 1998). LPS involve in the deposition of C3b onto LPS molecules at a position distant from the bacterial cell membrane that prevent the formation of lytic membrane attack complex (C5b–C9). As a result, the damage of the membrane as well as cell death do not take place (Podschun and Ullmann, 1998). Klebsiella oxytoca also produces numbers of adhesins that help the bacteria to adhere to the host cell which is a primary step for the bacteria to cause infections in the host cell. The bacteria attach to mucous or epithelial cells of the respiratory, intestinal and urogenital tracts through Type 1 pili and also bind to the mannose-containing trisaccharides of the host glycoproteins (Podschun and Ullmann, 1998). Type 3 pili is mannose resistant and agglutinate only tennin treated erythrocytes (Podschun and Ullmann, 1998). Resistance of Klebsiella spp. to current antibiotics like penicillins especially ampicillin and carbenicillin, cephalosporinases and carbapenemases and the oxyimino β-lactams such as cefotaxime, ceftazidime and the monobactam, aztreonam is increasing (Decre et al., 2004, Wu et al., 1991). Hence effective vaccination could be a better strategy in management of this pathogen. Reverse vaccinology (RV) could be a method of choice for identification of a potential vaccine candidate (Rappuoli, 2000). The method involves the screening of genomic information of the organism using computational tools. RV overcomes the problems in the conventional method of vaccine development by computationally predicting potential surface- exposed proteins from the genomic data (Rappuoli, 2000). Surface exposed proteins are mainly for the design of peptide vaccines, which can be recognized by the immune system to evoke immunity. The main components of peptide vaccines show B- and/or T- epitope activity which determine specificity of the immune response. Here, we have used computational methods for the identification of the surface exposed proteins of Klebsiella oxytoca which could be potent vaccine candidates. The effectiveness of the proposed vaccine candidates lies in the fact that they are the conserved surface proteins found across the strains of Klebsiella oxytoca. These proteins may prove to be useful for vaccination against any strain of Klebsiella oxytoca.

Section snippets

Materials and methodology

Pathway retrieval

Only 36 pathways were found to be common to all the strains of Klebsiella oxytoca but not present in human. The Klebsiella oxytoca strains are listed in Table 1 and the selected pathways are listed in Table 2.

Sub cellular localization prediction

We retrieved 626 proteins from the 36 pathways. The numbers of surface exposed proteins obtained from PSORTb v 3.0.2 analysis were 9, while 25 proteins were obtained from CELLO v.2.5. Then only the 8 proteins which have been classified as surface exposed both by PSORTb v 3.0.2 and CELLO v

Discussion

Klebsiella oxytoca is an organism with different strains and numerous serotypes present across the world. Here, we have proposed a novel in silico method to identify possible vaccine candidates for Klebsiella oxytoca which can be referred to as “Pan Genome Reverse Vaccinology” (Maione et al., 2005).The conservedness, immunogenicity, subcellular localization and unrelatedness with human proteome are the characteristic properties which are essential for a protein to be antigenic. In this work we

Conclusion

Although the need for clinical verification largely exists, at the primary level, this study shows that the above mentioned 6 proteins can be used as vaccine candidates against Klebsiella oxytoca. Moreover, as mentioned earlier these candidates can be effective against all the strains of Klebsiella Oxytoca globally present. We believe this will ease out the way for vaccine development against Klebsiella oxytoca.

References (45)

  • J. Sun et al.

    Bacterial multidrug efflux pumps: mechanisms, physiology and pharmacological exploitations

    Biochem. Biophys. Res. Commun.

    (2014)
  • H. Toobak et al.

    Immune response variations to Salmonella enterica serovar Typhi recombinant porin proteins in mice

    Biologicals

    (2013)
  • G. Adamus et al.

    Protection against keratoconjunctivitis shigellosa induced by immunization with outer membrane proteins of Shigella spp

    Infect. Immun.

    (1980)
  • S.N. Baalaji et al.

    Functional assay of Salmonella typhi OmpC using reconstituted large unilamellar vesicles: a general method for characterization of outer membrane proteins

    Biochimie

    (2006)
  • M.H. Chiang et al.

    Identification of novel vaccine candidates against Acinetobacter baumannii using reverse vaccinology

    Hum. Vaccin. Immunother.

    (2015)
  • E. De et al.

    A new mechanism of antibiotic resistance in Enterobacteriaceae induced by a structural modification of the major porin

    Mol. Microbiol.

    (2001)
  • D. Decre et al.

    Outbreak of multi-resistant Klebsiella oxytoca involving strains with extended spectrum beta-lactamases and strains with extended-spectrum activity of the chromosomal beta-lactamase

    J. Antimicrob. Chemother.

    (2004)
  • I.A. Doytchinova et al.

    VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines

    BMC Bioinformatics

    (2007)
  • A. Fenosa et al.

    Role of TolC in Klebsiella oxytoca resistance to antibiotics

    J. Antimicrob. Chemother.

    (2009)
  • D. Fourel et al.

    Specific regions of Escherichia coli OmpF protein involved in antigenic and colicin receptor sites and in stable trimerization

    J. Bacteriol.

    (1993)
  • I. Guilvout et al.

    Bacterial outer membrane secreting PulD assembles and inserts into the inner membrane in the absence of its pilotin

    EMBO J.

    (2006)
  • E.J. Hansen et al.

    Identification of immunogenic outer membrane proteins of Haemophilus influenzae type b in the infant rat model system

    Infect. Immun.

    (1981)

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