23 DOI: https://doi.org/10.1016/j.jgeb.2026.100772 English eng Safoura Moradkasani Contributor <div class="abstract author" id="as0005" style="margin: 0px 0px 8px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="st0010" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Background</h3><div class="u-margin-s-bottom" id="sp0075" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;"><em style="margin: 0px; padding: 0px;">Stenotrophomonas maltophilia</em> is a multidrug-resistant opportunistic pathogen causing severe hospital-acquired infections, especially in immunocompromised patients. The absence of an effective vaccine and rising antibiotic resistance underscore the need for novel interventions. This study employed an integrated reverse vaccinology and computational analyses to identify new immunogenic targets, design a multi-epitope vaccine (MEV), and propose potential drug targets<em style="margin: 0px; padding: 0px;">.</em></div></div><div class="abstract author" id="as0010" style="margin: 0px 0px 8px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="st0015" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Methods</h3><div class="u-margin-s-bottom" id="sp0080" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;">A comprehensive immunoinformatics pipeline was employed to assess antigenicity, allergenicity, human similarity, and physicochemical properties of <em style="margin: 0px; padding: 0px;">S. maltophilia</em> proteins. Both B- and T-cell epitopes were screened; however, only the top B-cell epitopes were selected for MEV construction, given the extracellular nature of <em style="margin: 0px; padding: 0px;">S. maltophilia</em>. MEV–TLR interactions were analyzed through molecular docking and dynamics simulations. In parallel, cytoplasmic proteins were screened <em style="margin: 0px; padding: 0px;">via</em> a subtractive genomics approach to identify essential, non-human homologous, and non-microbiome-similar proteins, which were further evaluated for druggability and interaction networks to propose novel therapeutic targets.</div></div><div class="abstract author" id="as0015" style="margin: 0px 0px 8px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="st0020" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Results</h3><div class="u-margin-s-bottom" id="sp0085" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;">From a total of 4111 proteins, seven potential immunogenic targets were identified: GspD (WP_108270537.1), FhuE (WP_049451370.1), fimbrial protein (WP_012479122.1), TonB-dependent receptor (WP_169448402.1), TolC family protein (WP_108270106.1), autotransporter beta-barrel OMP (WP_169448945.1), and a hypothetical protein (WP_005407892.1). Subsequently, an MEV was designed using five immunogenic epitopes derived from four of these targets: WP_005407892.1 (ADQDSSNM), WP_049451370.1 (SGKAEQ and GEESKTPS), WP_108270537.1 (GVTSTQSDSERT), and WP_169448945.1 (RELGGDRNE). Molecular docking and molecular dynamics simulations demonstrated strong, stable, and feasible interactions between the MEV and TLR-2 and TLR-4 receptors. Moreover, nine novel drug targets were predicted for <em style="margin: 0px; padding: 0px;">S. maltophilia</em>, providing new therapeutic insights.</div></div><div class="abstract author" id="as0020" style="margin: 0px 0px 8px; padding: 0px; color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, "Times New Roman", Times, STIXGeneral, "Cambria Math", "Lucida Sans Unicode", "Microsoft Sans Serif", "Segoe UI Symbol", "Arial Unicode MS", serif, sans-serif; font-size: 16px;"><h3 class="u-h4 u-margin-m-top u-margin-xs-bottom" id="st0025" style="margin-right: 0px; margin-left: 0px; padding: 0px; margin-top: 24px !important; margin-bottom: 8px !important; font-size: 20px !important; line-height: 30px !important;">Conclusion</h3><div class="u-margin-s-bottom" id="sp0090" style="margin-top: 0px; margin-right: 0px; margin-left: 0px; padding: 0px; margin-bottom: 16px !important;">The designed MEV and identified immunogenic targets represent promising vaccine candidates against <em style="margin: 0px; padding: 0px;">S. maltophilia</em>. Further <em style="margin: 0px; padding: 0px;">in vitro</em> and <em style="margin: 0px; padding: 0px;">in vivo</em> studies are essential to confirm their safety, immunogenicity, and protective efficacy. Additionally, subtractive genomics analysis revealed nine novel, non-homologous drug targets, offering safer and more specific therapeutic avenues.</div></div> Elsevier September 2026 pdf Journal of Genetic Engineering and Biotechnology Integrated immunoinformatics for the design of novel multi-epitope vaccine and identification of new drug targets against Stenotrophomonas maltophilia, a multidrug-resistant superbug mixed material Elsevier