Immuno-informatics driven proteome-wide investigation revealed novel peptide-based vaccine targets against emerging multiple drug resistant Providencia stuartii

被引:34
作者
Asad, Yelda [1 ]
Ahmad, Sajjad [1 ]
Rungrotmongkol, Thanyada [2 ,3 ]
Ranaghan, Kara E. [4 ]
Azam, Syed Sikander [1 ,2 ]
机构
[1] Quaid I Azam Univ, Computat Biol Lab, Natl Ctr Bioinformat, Islamabad 45320, Pakistan
[2] Chulalongkorn Univ, Dept Biochem, Biocatalyst & Environm Biotechnol Res Unit, Fac Sci, Bangkok 10330, Thailand
[3] Chulalongkorn Univ, PhD Program Bioinformat & Computat Biol, Fac Sci, Bangkok 10330, Thailand
[4] Univ Bristol, Ctr Computat Chem, Bristol, Avon, England
基金
英国生物技术与生命科学研究理事会;
关键词
Providencia stuartii; Reverse vaccinology; Subtractive proteomics; Epitopes; Fimbrial biogenesis outer membrane usher protein; REVERSE VACCINOLOGY; DRUGGABLE GENOME; PREDICTION; IDENTIFICATION; DATABASE; WEB; BACTERIURIA; ANNOTATION; BACTEREMIA; CANDIDATES;
D O I
10.1016/j.jmgm.2018.01.010
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
The bacterium Providencia stuartii, is associated with urinary tract infections and is the most common cause of purple urine bag syndrome. The increasing multi-drug resistance pattern shown by the pathogen and lack of licensed vaccines make treatment of infections caused by P. stuartii challenging. As vaccinology data against the pathogen is scarce, an in silico proteome based Reverse Vaccinology (RV) protocol, in combination with subtractive proteomics is introduced in this work to screen potential vaccine candidates against P. stuartii. The analysis identified three potential vaccine candidates for designing broad-spectrum and strain-specific peptide vaccines: FimD4, FimD6, and FimD8. These proteins are essential for pathogen survival, localized in the outer membrane, virulent, and antigenic in nature. Immunoproteomic tools mapped surface exposed and non-allergenic 9mer B-cell derived T-cell antigenic epitopes for the proteins. The epitopes also show stable and rich interactions with the most predominant HLA allele (DRB1*0101) in the human population. Metabolic pathway annotation of the proteins indicated that fimbrial biogenesis outer membrane usher protein (FimD6) is the most suitable candidate for vaccine design, due to its involvement in several significant pathways. These pathways include: the bacterial secretion system, two-component system, S-lactam resistance, and cationic antimicrobial peptide pathways. The predicted epitopes may provide a basis for designing a peptide-based vaccine against P. stuartii. (C) 2018 Elsevier Inc. All rights reserved.
引用
收藏
页码:238 / 250
页数:13
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