New putative therapeutic targets against Serratia marcescens using reverse vaccinology and subtractive genomics

Author(s):  
Ligia Carolina da Silva Prado ◽  
Andrei Giacchetto Felice ◽  
Thaís Cristina Vilela Rodrigues ◽  
Sandeep Tiwari ◽  
Bruno Silva Andrade ◽  
...  
2018 ◽  
Vol 15 (142) ◽  
pp. 20180032 ◽  
Author(s):  
Alissa de Sarom ◽  
Arun Kumar Jaiswal ◽  
Sandeep Tiwari ◽  
Letícia de Castro Oliveira ◽  
Debmalya Barh ◽  
...  

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.


2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Khurshid Jalal ◽  
Tareq Abu-Izneid ◽  
Kanwal Khan ◽  
Muhammad Abbas ◽  
Ajmal Hayat ◽  
...  

AbstractShigellosis is characterized as diarrheal disease that causes a high mortality rate especially in children, elderly and immunocompromised patients. More recently, the World Health Organization advised safe vaccine designing against shigellosis due to the emergence of Shigella dysenteriae resistant strains. Therefore, the aim of this study is to identify novel drug targets as well as the design of the potential vaccine candidates and chimeric vaccine models against Shigella dysenteriae. A computational based Reverse Vaccinology along with subtractive genomics analysis is one of the robust approaches used for the prioritization of drug targets and vaccine candidates through direct screening of genome sequence assemblies. Herein, a successfully designed peptide-based novel highly antigenic chimeric vaccine candidate against Shigella dysenteriae sd197 strain is proposed. The study resulted in six epitopes from outer membrane WP_000188255.1 (Fe (3+) dicitrate transport protein FecA) that ultimately leads to the construction of twelve vaccine models. Moreover, V9 construct was found to be highly immunogenic, non-toxic, non-allergenic, highly antigenic, and most stable in terms of molecular docking and simulation studies against six HLAs and TLRS/MD complex. So far, this protein and multiepitope have never been characterized as vaccine targets against Shigella dysenteriae. The current study proposed that V9 could be a significant vaccine candidate against shigellosis and to ascertain that further experiments may be applied by the scientific community focused on shigellosis.


2019 ◽  
Vol 6 (7) ◽  
pp. 190907 ◽  
Author(s):  
Thaís Cristina Vilela Rodrigues ◽  
Arun Kumar Jaiswal ◽  
Alissa de Sarom ◽  
Letícia de Castro Oliveira ◽  
Carlo José Freire Oliveira ◽  
...  

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.


2018 ◽  
Vol 125 ◽  
pp. 219-229 ◽  
Author(s):  
Hizbullah ◽  
Zarghoona Nazir ◽  
Sahib Gul Afridi ◽  
Mohibullah Shah ◽  
Sulaiman Shams ◽  
...  

2019 ◽  
Author(s):  
Sumit Mukherjee ◽  
Kaustav Gangopadhyay ◽  
Sunanda Biswas Mukherjee

ABSTRACTSalmonella enterica serovar typhi is the causative agent of typhoid fever in human. The available vaccine lacks the effectiveness and further overuse of the antibiotics throughout the past decades lead to the emergence of antibiotic-resistant strains. To reduce the spread of antibiotic resistance, it is essential to develop new vaccines. In this study using an extensive bioinformatic analysis based on reverse vaccinology and subtractive genomics-based approach, we searched the genome of S typhi. We found that two outermost membrane proteins LptD and LptE, which are responsible for the final transport of the LPS across the membrane having most of the essential signature for being vaccine target. Both of these proteins are found highly conserved and possess shared surface epitopes among several species of Salmonella pathogens. This indicates that these two proteins could be the potential target for vaccine development, which could be effective for a broad range of Salmonella pathogens.


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