Computational design and characterization of a multiepitope vaccine against carbapenemase-producing Klebsiella pneumoniae strains, derived from antigens identified through reverse vaccinology

Integration of immunoinformatics and cheminformatics to design and evaluate a multitope vaccine against Klebsiella pneumoniae and Pseudomonas aeruginosa coinfection

“…This was illustrated through lower values and minimal fluctuations for RMSDs, ROGs, RMSFs, and BSA tones regarding the binding proteins within the TLR4 complex system over TLR2 one. Our depicted TLR4-directed favored binding was in good agreement with reported data in the study by Cuscino et al evaluating a bioinformatic-designed multiepitope vaccine targeting carbapenemase-releasing K. pneumoniae strains (Cuscino et al, 2022).…”

“…The approach of computational vaccine design has been employed in several previous trials where some reports were only interested in the nomination of potential vaccine candidates (Nagpal et al, 2018;Mehmood et al, 2020) or started with a predefined virulent protein as potential vaccine candidates (Elhag et al, 2020;Mahapatra et al, 2021) and others extended their scope to include the epitope mapping and the construction of a multitope construct after protein candidates nomination (Cuscino et al, 2022;Wang et al, 2022). On the other hand, the current study exploited the option of mono epitopes integration and fused the mapped epitopes after the filtration of several vaccine candidates of two bacteria, K. pneumoniae and P. aeruginosa, to create a multitope construct with potential activity against the increasingly reported coinfection cases with those resistant bacteria.…”

“…Generally, TLR exists at the stage before downstream signal transduction in the C-shaped horse-shoe architecture (Park et al, 2009;Ohto et al, 2012). The inner concave surface of TLRs has been successfully investigated within current literature as the stable interface for different multi-epitope vaccines targeting different types of microbial organisms (Soltan et al, 2021;2022a;Cuscino et al, 2022). Focusing on vaccines targeting K. Pneumoniae, Dar et al reported successful affinity for their immunoinformatics-designed multiepitope vaccine towards the inner concave interfaces of both TLR4 and TLR2 (Dar et al, 2019).…”

Structural Insights into Amelioration Effects of Quercetin and Its Glycoside Derivatives on NAFLD in Mice by Modulating the Gut Microbiota and Host Metabolism

“…Deoxycholic acid, inducing DNA damage and enhancing liver carcinogenesis, was mainly formed from cholic acid by 7-alpha-dehydroxylase produced by the genus Clostridia in the gut . Genus Klebsiella such as Klebsiella pneumoniae was a Gram-negative pathogen of clinical relevance, which can result in serious infections and pneumonia .…”

“…45 Genus Klebsiella such as Klebsiella pneumoniae was a Gramnegative pathogen of clinical relevance, which can result in serious infections and pneumonia. 46 Staphylococcus and Streptococcus, two groups of major human pathogens, were thought to be able to scavenge host fatty acids. 47 The genus Flavonif ractor such as Flavonif ractor plautii, a potential pathogen, was related with the suppressed immune response in mice.…”