Abstract
Escherichia coli (E. coli) is a Gram-negative bacterium that belongs to the family Enterobacteriaceae. While E. coli can stay as an innocuous resident in the digestive tract, it can cause a group of symptoms ranging from diarrhea to live threatening complications. Due to the increased rate of antibiotic resistance worldwide, the development of an effective vaccine against E. coli pathotypes is a major health priority. In this study, a reverse vaccinology approach along with immunoinformatics has been applied for the detection of potential antigens to develop an effective vaccine. Based on our screening of 5,155 proteins, we identified lipopolysaccharide assembly protein (LptD) and outer membrane protein assembly factor (BamA) as vaccine candidates for the current study. The conservancy of these proteins in the main E. coli pathotypes was assessed through BLASTp to make sure that the designed vaccine will be protective against major E. coli pathotypes. The multitope vaccine was constructed using cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell lymphocyte (BCL) epitopes with suitable linkers and adjuvant. Following that, it was analyzed computationally where it was found to be antigenic, soluble, stable, and non-allergen. Additionally, the adopted docking study, as well as all-atom molecular dynamics simulation, illustrated the promising predicted affinity and free binding energy of this constructed vaccine against the human Toll-like receptor-4 (hTLR-4) dimeric state. In this regard, wet lab studies are required to prove the efficacy of the potential vaccine construct that demonstrated promising results through computational validation.
Highlights
According to its pathogenicity in humans, E. coli can be classified into an extraintestinal infection-causing E. coli and strains that cause enteric infections
Conservation analysis of our nominated vaccine candidates showed that these proteins were found with high conservation among various E. coli pathotypes (Supplementary Table 2) which confirmed their ability to protect against different E. coli
The binding affinity of the selected candidates of cytotoxic T lymphocyte (CTL) and helper T lymphocyte (HTL) was assessed through a docking study where the generated docked complexes for CTLs are shown in Supplementary Figure 1 and the docked complexes for HTLs are shown in Supplementary Figure 2
Summary
According to its pathogenicity in humans, E. coli can be classified into an extraintestinal infection-causing E. coli (primarily uropathogenic E. coli, UPEC, and neonatal meningitis E. coli, NMEC) and strains that cause enteric infections (divided into 6 pathotypes; enteropathogenic E. coli [EPEC], enterohemorrhagic E. coli [EHEC], enteroaggregative E. coli [EAEC], enteroinvasive E. coli [EIEC], enterotoxigenic E. coli [ETEC] and diffusely adherent E. coli [DAEC]). People can be infected with E. coli by swallowing a small amount of it in water, vegetables, or meat where the fecal-oral route is the major way of transmission [2]. Another common way of categorizing E. coli is by serotype through detection of surface antigens O and H. Pathogenic E. coli is a major public health concern because of possessing a low infectious dose and simple transmission through food and water [4]. An alternative solution to fight against this pathogen is designing an effective vaccine against its common pathotypes While this solution was adopted by many research groups around the world, there is no officially approved vaccine against pathogenic E. coli in the market [9]
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