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J R Soc Interface. 2018 May;15(142). pii: 20180032. doi: 10.1098/rsif.2018.0032.

Putative vaccine candidates and drug targets identified by reverse vaccinology and subtractive genomics approaches to control Haemophilus ducreyi, the causative agent of chancroid.

Author information

1
Institute of Biological Sciences and Natural Sciences, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.
2
Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
3
Centre for Genomics and Applied Gene Technology, Institute of Integrative Omics and Applied Biotechnology, Nonakuri, Purba Medinipur, West Bengal, India.
4
Institute of Biological Sciences and Natural Sciences, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil siomars@gmail.com.

Abstract

Chancroid is a sexually transmitted infection (STI) caused by the Gram-negative bacterium Haemophilus ducreyi The control of chancroid is difficult and the only current available treatment is antibiotic therapy; however, antibiotic resistance has been reported in endemic areas. Owing to recent outbreaks of STIs worldwide, it is important to keep searching for new treatment strategies and preventive measures. Here, we applied reverse vaccinology and subtractive genomic approaches for the in silico prediction of potential vaccine and drug targets against 28 strains of H. ducreyi We identified 847 non-host homologous proteins, being 332 exposed/secreted/membrane and 515 cytoplasmic proteins. We also checked their essentiality, functionality and virulence. Altogether, we predicted 13 candidate vaccine targets and three drug targets, where two vaccines (A01_1275, ABC transporter substrate-binding protein; and A01_0690, Probable transmembrane protein) and three drug targets (A01_0698, Purine nucleoside phosphorylase; A01_0702, Transcription termination factor; and A01_0677, Fructose-bisphosphate aldolase class II) are harboured by pathogenicity islands. Finally, we applied a molecular docking approach to analyse each drug target and selected ZINC77257029, ZINC43552589 and ZINC67912117 as promising molecules with favourable interactions with the target active site residues. Altogether, the targets identified here may be used in future strategies to control chancroid worldwide.

KEYWORDS:

Haemophilus ducreyi; chancroid; drug targets; molecular docking; reverse vaccinology; vaccine candidates

PMID:
29792307
PMCID:
PMC6000166
DOI:
10.1098/rsif.2018.0032
[Indexed for MEDLINE]
Free PMC Article

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