Core proteome mediated therapeutic target mining and multi-epitope vaccine design for Helicobacter pylori

被引:25
作者
Rahman, Noor [1 ]
Ajmal, Amar [2 ]
Ali, Fawad [3 ]
Rastrelli, Luca [4 ]
机构
[1] Univ Karachi, Int Ctr Chem & Biol Sci, HEJ Res Inst Chem, Karachi 75270, Pakistan
[2] Abdul Wali Khan Univ Mardan, Dept Biochem, Mardan 23200, KP, Pakistan
[3] Hazara Univ, Dept Biochem, Mansehra, Pakistan
[4] Univ Salerno, Dipartimento Farm, Via Giovanni Paolo II, I-84084 Fisciano, SA, Italy
关键词
Helicobactor pylori; Multi-epitope vaccine; Antigenic; Immunoinformatics; POTENTIAL-DRUG TARGETS; SUBTRACTIVE GENOME ANALYSIS; VIRULENCE FACTORS; IDENTIFICATION; PREDICTION; INFECTION; SEQUENCE; GENE;
D O I
10.1016/j.ygeno.2020.06.026
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Helicobacter pylori is a Gram-negative spiral-shaped bacterium that infects half of the human population worldwide and causes chronic inflammation. In the present study, we used the art of computational biology for therapeutic drug targets identification and a multi-epitope vaccine against multi-strains of H. pylori. For drug target identification, we used different tools and softwares to identify human non-homologous but pathogen essential proteins, with virulent properties and involved in unique metabolic pathways of H. pylon. For this purpose, the core proteome of 84 strains of H. pylori was retrieved from EDGAR 2.3 database. There were 59,808 proteins sequences in these strains. Duplicates and paralogous protein sequence removal was followed by human non-homologous protein miningPathogen essential and virulent proteins were subjected to pathway analysis Subcellular localization of the virulent proteins was predicted and druggability was also checked, leading to 30 druggable targets based on their similarity with the approved drug targets in Drugbank. For immunoinformatics analysis, we selected two outer membrane proteins (HPAKL86_RS06305 and HPSNT_RS00950) and subjected to determined immunogenic B and T-Cell epitopes. The B and T-Cell overlapped epitopes were selected to design 9 different vaccine constructs by using linkers and adjuvants. Least allergenic and most antigenic construct (C-8) was selected as a promiscuous vaccine to elicit host immune response. Cloning and in silico expression of the constructed vaccine (C-8) was done to produce a clone having the desired (gene) vaccine construct. In conclusion, the prioritized therapeutic targets for 84 strains of H.pylori will be useful for future therapy design. Vaccine design may also prove useful in the quest for targeting multi-strains of H. pylori in patients.
引用
收藏
页码:3473 / 3483
页数:11
相关论文
共 39 条
[21]   SOLpro: accurate sequence-based prediction of protein solubility [J].
Magnan, Christophe N. ;
Randall, Arlo ;
Baldi, Pierre .
BIOINFORMATICS, 2009, 25 (17) :2200-2207
[22]   FireDock: a web server for fast interaction refinement in molecular docking [J].
Mashiach, Efrat ;
Schneidman-Duhovny, Dina ;
Andrusier, Nelly ;
Nussinov, Ruth ;
Wolfson, Haim J. .
NUCLEIC ACIDS RESEARCH, 2008, 36 :W229-W232
[23]   KAAS: an automatic genome annotation and pathway reconstruction server [J].
Moriya, Yuki ;
Itoh, Masumi ;
Okuda, Shujiro ;
Yoshizawa, Akiyasu C. ;
Kanehisa, Minoru .
NUCLEIC ACIDS RESEARCH, 2007, 35 :W182-W185
[24]   Identification of putative vaccine candidates against Helicobacter pylori exploiting exoproteome and secretome: A reverse vaccinology based approach [J].
Naz, Anam ;
Awan, Faryal Mehwish ;
Obaid, Ayesha ;
Muhammad, Syed Aun ;
Paracha, Rehan Zafar ;
Ahmad, Jamil ;
Ali, Amjad .
INFECTION GENETICS AND EVOLUTION, 2015, 32 :280-291
[25]  
Neelapu Nageswara R. R., 2015, Infectious Disorders - Drug Targets, V15, P106
[26]   Helicobacter pylori virulence factors and the host immune response:: implications for therapeutic vaccination [J].
Prinz, C ;
Hafsi, N ;
Voland, P .
TRENDS IN MICROBIOLOGY, 2003, 11 (03) :134-138
[27]   Identification of potential drug targets by subtractive genome analysis of Bacillus anthracis A0248: An in silico approach [J].
Rahman, Md. Anisur ;
Noore, Md. Sanaullah ;
Hasan, Md. Anayet ;
Ullah, Md. Rakib ;
Rahman, Md. Hafijur ;
Hossain, Md. Amzad ;
Ali, Yeasmeen ;
Islam, Md. Saiful .
COMPUTATIONAL BIOLOGY AND CHEMISTRY, 2014, 52 :66-72
[28]   In-silico Subtractive Proteomic Analysis Approach for Therapeutic Targets in MDR Salmonella enterica subsp. enterica serovar Typhi str. CT18 [J].
Rahman, Noor ;
Muhammad, Ijaz ;
Nayab, Gul E. ;
Khan, Haroon ;
Filosa, Rosanna ;
Xiao, Jianbo ;
Hassan, Sherif T. S. .
CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2019, 19 (29) :2708-2717
[29]  
Saha S, 2004, LECT NOTES COMPUT SC, V3239, P197
[30]   AlgPred: prediction of allergenic proteins and mapping of IgE epitopes [J].
Saha, Sudipto ;
Raghava, G. P. S. .
NUCLEIC ACIDS RESEARCH, 2006, 34 :W202-W209