Identificação in silico de prováveis alvos vacinais e de fármacos contra Haemophilus ducreyi: uma abordagem em vacinologia reversa e genômica subtrativa

Abstract

Chancroid is a sexually transmitted infection (STI) caused by the Gram-negative bacterium Haemophilus ducreyi. The control of chancroid is difficult because an earlier infection by H. ducreyi does not induce an appropriate adaptative immune response and the conventional antigen screening methods have been unsuccessful in finding suitable target molecules. The only current available treatment is with antibiotic; however, resistance has been reported in endemic areas. Due 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 H. ducreyi. We identified the non-host homologous proteins and predicted their subcellular localization, essentiality, functionality and virulence. Altogether, we predicted 13 candidate vaccine targets and 3 drug targets,where 2 vaccine (A01_1275 and A01_0690) and 3 drug targets (A01_0698, A01_0702, and A01_0677) are harbored by pathogenicity islands. Finally, we applied a molecular docking approach to analyze each drug target and selected ZINC77257029, ZINC43552589, and ZINC67912117 as promising molecules with favorable interactions with the targets active site residues. Altogether, the targets identified here may be used in future strategies to control chancroid worldwide.