Reverse vaccinology and subtractive genomics reveal new therapeutic targets against Mycoplasma pneumoniae: a causative agent of pneumonia.

Pneumonia is an infectious disease caused by bacteria, viruses or fungi that results in millions of deaths globally. Despite the existence of prophylactic methods against some of the major pathogens of the disease, there is no efficient prophylaxis against atypical agents such as Mycoplasma pneumoniae, a bacterium associated with cases of community-acquired pneumonia. Because of the morphological peculiarity of M. pneumoniae, which leads to an increased resistance to antibiotics, studies that prospectively investigate the development of vaccines and drug targets appear to be one of the best ways forward. Hence, in this paper, bioinformatics tools were used for vaccine and pharmacological prediction. We conducted comparative genomic analysis on the genomes of 88 M. pneumoniae strains, as opposed to a reverse vaccinology analysis, in relation to the capacity of M. pneumoniae proteins to bind to the major histocompatibility complex, revealing seven targets with immunogenic potential. Predictive cytoplasmic proteins were tested as potential drug targets by studying their structures in relation to other proteins, metabolic pathways and molecular anchorage, which identified five possible drug targets. These findings are a valuable addition to the development of vaccines and the selection of new in vivo drug targets that may contribute to further elucidating the molecular basis of M. pneumoniae-host interactions.

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

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.