{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:09:04Z","timestamp":1780553344465,"version":"3.54.1"},"reference-count":149,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T00:00:00Z","timestamp":1780531200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    <jats:italic>Acinetobacter baumannii<\/jats:italic>\n                    is a multidrug-resistant (MDR) nosocomial pathogen associated with exceptionally high mortality, underscoring the urgent need for immune-based strategies that operate independently of antibiotic susceptibility. The Zonula occludens toxin (Zot), a barrier-disrupting virulence factor embedded within mobile genetic elements, has recently been proposed as a conserved component of clinically relevant\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    lineages, however, its immunological architecture remains poorly defined. Here, we applied an integrated immunoinformatic and evolutionary framework to evaluate Zot as a target for adaptive immune recognition and immunotherapeutic intervention. Comparative analysis of 62 full-length Zot homologs revealed structured sequence diversity superimposed on near-complete alignment continuity, consistent with structural constraint maintaining protein integrity. Structural modeling demonstrated that deep sequence divergence between historical and contemporary isolates does not disrupt the overall Zot fold, indicating conservation of antigenic architecture. High-resolution epitope mapping identified multiple potential B-cell\u2013accessible regions and dense clusters of conserved MHC Class I and Class II binding motifs, particularly within a compact C-terminal domain exhibiting strong sequence and structural constraint. Notably, predicted T-cell epitopes remained resilient across divergent strains, consistent with conserved MHC anchor residue architecture. Together, these findings suggest that Zot may represent a structurally constrained immunological target with features consistent with both humoral and cell-mediated immune engagement across genetically diverse\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    backgrounds. This immune-centric characterization provides a mechanistic foundation for immunotherapeutic targeting of Zot and supports its prioritization for further experimental evaluation in vaccine development pipelines targeting MDR\n                    <jats:italic>A. baumannii<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1835523","type":"journal-article","created":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:43:32Z","timestamp":1780551812000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["High resolution immunoinformatic profiling of Zonula occludens toxin reveals a conserved multiepitope vaccine candidate in Acinetobacter baumannii"],"prefix":"10.3389","volume":"17","author":[{"given":"Payam","family":"Benyamini","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, College of Medicine, Charles R. Drew University","place":["Los Angeles, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,4]]},"reference":[{"key":"B1","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-031-62839-9_13","article-title":"Significance of bacterial toxins","volume-title":"Microbial Toxins in Food Systems: Causes, Mechanisms, Complications, and Metabolism","author":"Osman","year":"2024"},{"key":"B2","volume-title":"The comprehensive sourcebook of bacterial protein toxins","author":"Alouf","year":"2005"},{"key":"B3","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1128\/mmbr.00052-12","article-title":"Role of pore-forming toxins in bacterial infectious diseases","volume":"77","author":"Los","year":"2013","journal-title":"Microbiol Mol Biol Rev"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.001154","article-title":"Bacterial pore-forming toxins","volume":"168","author":"Ulhuq","year":"2022","journal-title":"Microbiology"},{"key":"B5","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-50580-0","volume-title":"Shiga toxins: a review of structure, mechanism, and detection","author":"Silva","year":"2017"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.149.6.2089","article-title":"Diphtheria toxin-and Pseudomonas A toxin-mediated apoptosis. ADP ribosylation of elongation factor-2 is required for DNA fragmentation and cell lysis and synergy with tumor necrosis factor-\u03b1","volume":"149","author":"Morimoto","year":"1992","journal-title":"J Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.17816\/eid321328","article-title":"Structure and mechanism of action of botulinum and tetanus neurotoxins: a review","volume":"28","author":"Skryabina","year":"2023","journal-title":"Epidemiol Infect Dis"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/s0016-5085(00)85399-8","article-title":"Zonula occludens toxin structure-function analysis: identification of the fragment biologically active on tight junctions and of the zonulin receptor binding domain","volume":"276","author":"Di Pierro","year":"2001","journal-title":"J Biol Chem"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/b0-12-386860-2\/00232-x","article-title":"Clostridium difficile toxins disrupt epithelial barrier function by altering membrane microdomain localization of tight junction proteins","volume":"69","author":"Nusrat","year":"2001","journal-title":"Infect Immun"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijmm.2005.06.011","article-title":"Interplay of bacterial toxins with host defence: molecular mechanisms of immunomodulatory signalling","volume":"295","author":"Backert","year":"2005","journal-title":"Int J Med Microbiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2006.07.002","article-title":"Anthrax toxins: a paradigm of bacterial immune suppression","volume":"27","author":"Baldari","year":"2006","journal-title":"Trends Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.18.012502.134748","article-title":"Bacterial toxins that modify the actin cytoskeleton","volume":"18","author":"Barbieri","year":"2002","journal-title":"Annu Rev Cell Dev Biol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.3390\/toxins1020123","article-title":"Actin crosslinking toxins of Gram-negative bacteria","volume":"1","author":"Satchell","year":"2009","journal-title":"Toxins"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3390\/toxins8050134","article-title":"Clostridium difficile toxins A and B: insights into pathogenic properties and extraintestinal effects","volume":"8","author":"Di Bella","year":"2016","journal-title":"Toxins"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/toxins2082158","article-title":"Different types of cell death induced by enterotoxins","volume":"2","author":"Lin","year":"2010","journal-title":"Toxins"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12088-016-0625-1","article-title":"Bacterial virulence factors: secreted for survival","volume":"57","author":"Sharma","year":"2017","journal-title":"Indian J Microbiol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3390\/toxins16040182","article-title":"Overview of bacterial protein toxins from pathogenic bacteria: mode of action and insights into evolution","volume":"16","author":"Popoff","year":"2024","journal-title":"Toxins"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1081\/txr-120014408","article-title":"Structure and function of diphtheria toxin: from pathology to engineering","volume":"21","author":"Chenal","year":"2002","journal-title":"J Toxicol Toxin Rev"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1002199107","article-title":"Structural organization of the functional domains of Clostridium difficile toxins A and B","volume":"107","author":"Pruitt","year":"2010","journal-title":"Proc Natl Acad Sci"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1172\/jci24609","article-title":"Pertussis toxin inhibits neutrophil recruitment to delay antibody-mediated clearance of Bordetella pertussis","volume":"115","author":"Kirimanjeswara","year":"2005","journal-title":"J Clin Invest"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.4103\/0971-5916.79093","article-title":"Cholera toxin: a paradigm of a multifunctional protein","volume":"133","author":"Bharati","year":"2011","journal-title":"Indian J Med Res"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/jci118114","article-title":"Zonula occludens toxin modulates tight junctions through protein kinase C-dependent actin reorganization, in vitro","volume":"96","author":"Fasano","year":"1995","journal-title":"J Clin Invest"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25189780","article-title":"The comparative characterization of a hypervirulent acinetobacter baumannii bacteremia clinical isolate reveals a novel mechanism of pathogenesis","volume":"25","author":"Benyamini","year":"2024","journal-title":"Int J Mol Sci"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/toxins16060271","article-title":"Phylogenetic tracing of evolutionarily conserved zonula occludens toxin reveals a \u201cHigh Value\u201d vaccine candidate specific for treating multi-strain Pseudomonas aeruginosa infections","volume":"16","author":"Benyamini","year":"2024","journal-title":"Toxins"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1038\/s41580-022-00465-y","article-title":"Apical\u2013basal polarity and the control of epithelial form and function","volume":"23","author":"Buckley","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2017.1345353","article-title":"In life there is death: How epithelial tissue barriers are preserved despite the challenge of apoptosis","volume":"5","author":"Duszyc","year":"2017","journal-title":"Tissue Barriers"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1038\/nri3608","article-title":"Intestinal epithelial cells: regulators of barrier function and immune homeostasis","volume":"14","author":"Peterson","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1002\/j.2040-4603.2017.tb00785.x","article-title":"Epithelial organization: the gut and beyond","volume":"7","author":"Shashikanth","year":"2017","journal-title":"Compr Physiol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a002584","article-title":"Physiology and function of the tight junction","volume":"1","author":"Anderson","year":"2009","journal-title":"Cold Spring Harbor Perspect Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.22.010305.104219","article-title":"Tight junctions and cell polarity","volume":"22","author":"Shin","year":"2006","journal-title":"Annu Rev Cell Dev Biol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-008-0424-9","article-title":"Tight junction-based epithelial microenvironment and cell proliferation","volume":"27","author":"Tsukita","year":"2008","journal-title":"Oncogene"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22052506","article-title":"Tight junctions as a key for pathogens invasion in intestinal epithelial cells","volume":"22","author":"Paradis","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B33","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s00418-008-0424-9","article-title":"Tight junctions and the modulation of barrier function in disease","volume":"130","author":"F\u00f6rster","year":"2008","journal-title":"Histochem Cell Biol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1080\/21688370.2015.1138017","article-title":"Tight junction modulation of the blood brain barrier: CNS delivery of small molecules","volume":"4","author":"Greene","year":"2016","journal-title":"Tissue barriers"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.113.24.4435","article-title":"Human zonulin, a potential modulator of intestinal tight junctions","volume":"113","author":"Wang","year":"2000","journal-title":"J Cell Sci"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2007.05.051","article-title":"Tight junction modulation and biochemical characterisation of the zonula occludens toxin C-and N-termini","volume":"581","author":"Schmidt","year":"2007","journal-title":"FEBS Lett"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb05244.x","article-title":"Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin","volume":"915","author":"Fasano","year":"2000","journal-title":"Ann N Y Acad Sci"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1128\/cmr.00058-07","article-title":"Acinetobacter baumannii: emergence of a successful pathogen","volume":"21","author":"Peleg","year":"2008","journal-title":"Clin Microbiol Rev"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000000036","article-title":"Epidemiologic and clinical impact of Acinetobacter baumannii colonization and infection: a reappraisal","volume":"93","author":"Villar","year":"2014","journal-title":"Medicine"},{"key":"B40","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1097\/mrm.0000000000000339","article-title":"Prevalence of Acinetobacter baumannii with multiple drug resistance isolated from patients with ventilator-associated pneumonia from 2010 to 2020 in the world: A systematic review and meta-analysis","volume":"35","author":"Panahi","year":"2024","journal-title":"Rev Res Med Microbiol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1097\/inf.0b013e31827c97ba","article-title":"Clinical features, risk factors, and outcome of carbapenem-resistant Acinetobacter baumannii bacteremia in a Thai neonatal intensive care unit","volume":"6","author":"Nakwan","year":"2012","journal-title":"Asian BioMed"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmii.2011.12.009","article-title":"Risk factors and clinical outcomes of patients with carbapenem-resistant Acinetobacter baumannii bacteremia","volume":"45","author":"Huang","year":"2012","journal-title":"J Microbiol Immunol Infect"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.5799\/ahinjs.02.2013.04.0101","article-title":"Risk factors for nosocomial Acinetobacter bacteremia: a case-control study of intensive care unit patients","volume":"3","author":"T\u00fcnger","year":"2013","journal-title":"J Microbiol Infect Dis"},{"key":"B44","doi-asserted-by":"publisher","first-page":"49","DOI":"10.3390\/medicina55020049","article-title":"Ventilator-associated pneumonia due to drug-resistant Acinetobacter baumannii: risk factors and mortality relation with resistance profiles, and independent predictors of in-hospital mortality","volume":"55","author":"\u010ciginskien\u0117","year":"2019","journal-title":"Medicina"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2020.115229","article-title":"Risk factors and outcomes of bloodstream infections caused by Acinetobacter baumannii: a case\u2013control study","volume":"99","author":"Gu","year":"2021","journal-title":"Diagn Microbiol Infect Dis"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajic.2015.12.012","article-title":"The influence of biofilm formation and multidrug resistance on environmental survival of clinical and environmental isolates of Acinetobacter baumannii","volume":"44","author":"Greene","year":"2016","journal-title":"Am J infection control"},{"key":"B47","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/s12199-017-0653-4","article-title":"Detection of antibiotic resistant Acinetobacter baumannii in various hospital environments: potential sources for transmission of Acinetobacter infections","volume":"22","author":"Shamsizadeh","year":"2017","journal-title":"Environ Health Preventative Med"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1086\/653201","article-title":"Frequent multidrug-resistant Acinetobacter baumannii contamination of gloves, gowns, and hands of healthcare workers","volume":"31","author":"Morgan","year":"2010","journal-title":"Infection Control Hosp Epidemiol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1111\/lam.12627","article-title":"Evaluation of the ability of Acinetobacter baumannii to form biofilms on six different biomedical relevant surfaces","volume":"63","author":"Greene","year":"2016","journal-title":"Lett Appl Microbiol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2006.08.035","article-title":"Carbapenem-resistant Acinetobacter baumannii: an emerging threat for patients with post-neurosurgical meningitis","volume":"29","author":"Metan","year":"2007"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1128\/genomeA.00583-16","article-title":"Complete genome sequence of a multidrug-resistant Acinetobacter baumannii isolate obtained from a Mexican hospital (sequence type 422)","volume":"4","author":"Castro-Jaimes","year":"2016","journal-title":"Genome Announcements"},{"key":"B52","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1186\/s12866-023-02961-3","article-title":"Occurrence of Acinetobacter baumannii genomic resistance islands (AbGRIs) in Acinetobacter baumannii strains belonging to global clone 2 obtained from COVID-19 patients","volume":"23","author":"Naderi","year":"2023","journal-title":"BMC Microbiol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066584","article-title":"Complete genome analysis of three Acinetobacter baumannii clinical isolates in China for insight into the diversification of drug resistance elements","volume":"8","author":"Zhu","year":"2013","journal-title":"PloS One"},{"key":"B54","doi-asserted-by":"publisher","first-page":"16961","DOI":"10.1038\/s41598-018-35377-5","article-title":"Genome sequence analysis of an extensively drug-resistant Acinetobacter baumannii indigo-pigmented strain depicts evidence of increase genome plasticity","volume":"8","author":"Traglia","year":"2018","journal-title":"Sci Rep"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008995","article-title":"Acinetobacter baumannii can use multiple siderophores for iron acquisition, but only acinetobactin is required for virulence","volume":"16","author":"Sheldon","year":"2020","journal-title":"PloS Pathog"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0017027","article-title":"Acinetobacter baumannii secretes cytotoxic outer membrane protein A via outer membrane vesicles","volume":"6","author":"Jin","year":"2011","journal-title":"PloS One"},{"key":"B57","volume-title":"Outer membrane vesicles of Acinetobacter baumannii","author":"Frampton","year":"2007"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2017.08.001","article-title":"Acinetobacter baumannii virulence is enhanced by the combined presence of virulence factors genes phospholipase C (plcN) and elastase (lasB)","volume":"110","author":"Kareem","year":"2017","journal-title":"Microb Pathogen"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0138360","article-title":"Acinetobacter baumannii virulence is mediated by the concerted action of three phospholipases D","volume":"10","author":"Stahl","year":"2015","journal-title":"PloS One"},{"key":"B60","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1007\/s00203-025-04668-7","article-title":"Virulence arsenal of Acinetobacter baumannii: mechanisms driving persistence and resistance","volume":"208","author":"Ayswarya","year":"2026","journal-title":"Arch Microbiol"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1093\/femspd\/ftz004","article-title":"Tug of war between Acinetobacter baumannii and host immune responses","volume":"76","author":"Li","year":"2018","journal-title":"Pathog Dis"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1086\/590568","article-title":"Acinetobacter baumannii skin and soft-tissue infection associated with war trauma","volume":"47","author":"Sebeny","year":"2008","journal-title":"Clin Infect Dis"},{"key":"B63","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1089\/sur.2009.022","article-title":"Acinetobacter baumannii-associated skin and soft tissue infections: recognizing a broadening spectrum of disease","volume":"11","author":"Guerrero","year":"2010","journal-title":"Surg Infections"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/s1473-3099(09)70055-6","article-title":"Management of meningitis due to antibiotic-resistant Acinetobacter species","volume":"9","author":"Kim","year":"2009","journal-title":"Lancet Infect Dis"},{"key":"B65","doi-asserted-by":"publisher","first-page":"281","DOI":"10.3390\/antibiotics10030281","article-title":"The role of antibiotic resistant A. baumannii in the pathogenesis of urinary tract infection and the potential of its treatment with the use of bacteriophage therapy","volume":"10","author":"Bagi\u0144ska","year":"2021","journal-title":"Antibiotics"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcdt.2017.01.003","article-title":"Acinetobacter baumannii in ICU patients: A prospective study highlighting their incidence, antibiotic sensitivity pattern and impact on ICU stay and mortality","volume":"66","author":"Sileem","year":"2017","journal-title":"Egyptian J Chest Dis Tuberculosis"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.2174\/1381612811306020223","article-title":"The rise of carbapenem-resistant Acinetobacter baumannii","volume":"19","author":"Evans","year":"2013","journal-title":"Curr Pharm Des"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6968.2006.00195.x","article-title":"The role of IS Aba1 in expression of OXA carbapenemase genes in Acinetobacter baumannii","volume":"258","author":"Turton","year":"2006","journal-title":"FEMS Microbiol Lett"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01388-10","article-title":"Efflux-mediated antibiotic resistance in Acinetobacter spp","volume":"55","author":"Coyne","year":"2011","journal-title":"Antimicrob Agents Chemother"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1159\/000238887","article-title":"Imipenem resistance in Acinetobacter baumanii is due to altered penicillin-binding proteins","volume":"37","author":"Gehrlein","year":"1991","journal-title":"Chemotherapy"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl509","article-title":"Porins, efflux pumps and multidrug resistance in Acinetobacter baumannii","volume":"59","author":"Vila","year":"2007","journal-title":"J Antimicrob Chemother"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.01001-22","article-title":"Peptidoglycan recycling promotes outer membrane integrity and carbapenem tolerance in Acinetobacter baumannii","volume":"13","author":"Islam","year":"2022","journal-title":"MBio"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1128\/spectrum.00173-22","article-title":"An outer membrane protein YiaD contributes to adaptive resistance of meropenem in Acinetobacter baumannii","volume":"10","author":"Han","year":"2022","journal-title":"Microbiol Spectr"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2020.1855912","article-title":"Virulence role of the outer membrane protein CarO in carbapenem-resistant Acinetobacter baumannii","volume":"11","author":"Labrador-Herrera","year":"2020","journal-title":"Virulence"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2007.04.024","article-title":"Prognosis of adult patients with bacteremia caused by extensively resistant Acinetobacter baumannii","volume":"59","author":"Tseng","year":"2007","journal-title":"Diagn Microbiol Infect Dis"},{"key":"B76","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1186\/s13756-023-01343-8","article-title":"Acinetobacter baumannii: assessing susceptibility patterns, management practices, and mortality predictors in a tertiary teaching hospital in Lebanon","volume":"12","author":"Itani","year":"2023","journal-title":"Antimicrobial Resistance Infection Control"},{"key":"B77","doi-asserted-by":"publisher","first-page":"2608","DOI":"10.21037\/jtd.2018.04.86","article-title":"Risk factors for mortality in ICU patients with Acinetobacter baumannii ventilator-associated pneumonia: impact of bacterial cytotoxicity","volume":"10","author":"Ju","year":"2018","journal-title":"J Thorac Dis"},{"key":"B78","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1186\/s40560-015-0077-4","article-title":"Prognostic factors associated with mortality of drug-resistant Acinetobacter baumannii ventilator-associated pneumonia","volume":"3","author":"Inchai","year":"2015","journal-title":"J Intensive Care"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2006.04.084","article-title":"Post-genomic vaccine development","volume":"580","author":"Serruto","year":"2006","journal-title":"FEBS Lett"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1016\/s1369-5274(00)00119-3","article-title":"Reverse vaccinology","volume":"3","author":"Rappuoli","year":"2000","journal-title":"Curr Opin Microbiol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2015.1010910","article-title":"Identification of novel vaccine candidates against Acinetobacter baumannii using reverse vaccinology","volume":"11","author":"Chiang","year":"2015","journal-title":"Hum Vaccines Immunotherapeutics"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2021.105138","article-title":"Putative novel B-cell vaccine candidates identified by reverse vaccinology and genomics approaches to control Acinetobacter baumannii serotypes","volume":"96","author":"Beiranvand","year":"2021","journal-title":"Infection Genet Evol"},{"key":"B83","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1186\/s12879-025-11242-5","article-title":"Immunoinformatics-based development of a multi-epitope vaccine candidate targeting coinfection by Klebsiella pneumoniae and Acinetobacter baumannii","volume":"25","author":"Afshan","year":"2025","journal-title":"BMC Infect Dis"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-022-03995-5","article-title":"Identification of antigenic properties of Acinetobacter baumannii proteins as novel putative vaccine candidates using reverse vaccinology approach","volume":"194","author":"Piri-Gharaghie","year":"2022","journal-title":"Appl Biochem Biotechnol"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkh340","article-title":"MUSCLE: multiple sequence alignment with high accuracy and high throughput","volume":"32","author":"Edgar","year":"2004","journal-title":"Nucleic Acids Res"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-5-113","article-title":"MUSCLE: a multiple sequence alignment method with reduced time and space complexity","volume":"5","author":"Edgar","year":"2004","journal-title":"BMC Bioinf"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msp146","article-title":"Structural determinants of protein evolution are context-sensitive at the residue level","volume":"26","author":"Franzosa","year":"2009","journal-title":"Mol Biol Evol"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0510098103","article-title":"Protein stability promotes evolvability","volume":"103","author":"Bloom","year":"2006","journal-title":"Proc Natl Acad Sci"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2762","article-title":"Structural and functional constraints in the evolution of protein families","volume":"10","author":"Worth","year":"2009","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B90","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/s0378-1097(00)00478-x","article-title":"Purification and preliminary characterization of the zonula occludens toxin receptor from human (CaCo2) and murine (IEC6) intestinal cell lines","volume":"194","author":"Uzzau","year":"2001","journal-title":"FEMS Microbiol Lett"},{"key":"B91","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1093\/protein\/12.2.85","article-title":"Twilight zone of protein sequence alignments","volume":"12","author":"Rost","year":"1999","journal-title":"Protein Eng"},{"key":"B92","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1002\/prot.22458","article-title":"Structure is three to ten times more conserved than sequence\u2014a study of structural response in protein cores","volume":"77","author":"Illerg\u00e5rd","year":"2009","journal-title":"Proteins: Structure Function Bioinf"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1038\/nrg.2015.18","article-title":"Causes of evolutionary rate variation among protein sites","volume":"17","author":"Echave","year":"2016","journal-title":"Nat Rev Genet"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/149.1.445","article-title":"Assessing the impact of secondary structure and solvent accessibility on protein evolution","volume":"149","author":"Goldman","year":"1998","journal-title":"Genetics"},{"key":"B95","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1093\/molbev\/mss217","article-title":"Integrating sequence variation and protein structure to identify sites under selection","volume":"30","author":"Meyer","year":"2013","journal-title":"Mol Biol Evol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.1101\/2022.09.21.508815","article-title":"From motor protein to toxin: Mutations in the zonula occludens toxin (Zot) of Vibrio cholerae phage CTX\u03d5 suggest a loss of phage assembly function","author":"Ma","year":"2022","journal-title":"bioRxiv"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.88.12.5242","article-title":"Vibrio cholerae produces a second enterotoxin, which affects intestinal tight junctions","volume":"88","author":"Fasano","year":"1991","journal-title":"Proc Natl Acad Sci"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00302","article-title":"The structural basis of antibody-antigen recognition","volume":"4","author":"Sela-Culang","year":"2013","journal-title":"Front Immunol"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1110\/ps.062405906","article-title":"Prediction of residues in discontinuous B\u2010cell epitopes using protein 3D structures","volume":"15","author":"Haste Andersen","year":"2006","journal-title":"Protein Sci"},{"key":"B100","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1146\/annurev.iy.13.040195.003103","article-title":"The three-dimensional structure of peptide-MHC complexes","volume":"13","author":"Madden","year":"1995","journal-title":"Annu Rev Immunol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1016\/s0022-2836(03)00750-2","article-title":"Sequence variability analysis of human class I and class II MHC molecules: functional and structural correlates of amino acid polymorphisms","volume":"331","author":"Reche","year":"2003","journal-title":"J Mol Biol"},{"key":"B102","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1007\/bf00172063","article-title":"MHC ligands and peptide motifs: first listing","volume":"41","author":"Rammensee","year":"1995","journal-title":"Immunogenetics"},{"key":"B103","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-59259-890-8_51","article-title":"Computational identification of related proteins: BLAST, PSI-BLAST, and other tools","volume-title":"The Proteomics Protocols Handbook.","author":"Dong","year":"2005"},{"key":"B104","article-title":"[27] local alignment statistics","volume-title":"Methods in Enzymology","author":"Altschul","year":"1996"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi0301s42","article-title":"An introduction to sequence similarity (\u201chomology\u201d) searching","volume":"42","author":"Pearson","year":"2013","journal-title":"Curr Protoc Bioinf"},{"key":"B106","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1146\/annurev.biophys.31.082901.134314","article-title":"The natural history of protein domains","volume":"31","author":"Ponting","year":"2002","journal-title":"Annu Rev Biophysics Biomolecular Structure"},{"key":"B107","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1038\/35012500","article-title":"Lateral gene transfer and the nature of bacterial innovation","volume":"405","author":"Ochman","year":"2000","journal-title":"Nature"},{"key":"B108","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2008.09.004","article-title":"Bacteriophage genomics","volume":"11","author":"Hatfull","year":"2008","journal-title":"Curr Opin Microbiol"},{"key":"B109","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1046\/j.1365-2958.2003.03580.x","article-title":"Prophages and bacterial genomics: what have we learned so far","volume":"49","author":"Casjens","year":"2003","journal-title":"Mol Microbiol"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1128\/mmbr.67.3.473.2003","article-title":"Prophage genomics","volume":"67","author":"Canchaya","year":"2003","journal-title":"Microbiol Mol Biol Rev"},{"key":"B111","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1986.tb04288.x","article-title":"The relation between the divergence of sequence and structure in proteins","volume":"5","author":"Chothia","year":"1986","journal-title":"EMBO J"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1093\/gbe\/evu225","article-title":"The genomic diversification of the whole Acinetobacter genus: origins, mechanisms, and consequences","volume":"6","author":"Touchon","year":"2014","journal-title":"Genome Biol Evol"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1104404108","article-title":"Genome-wide recombination drives diversification of epidemic strains of Acinetobacter baumannii","volume":"108","author":"Snitkin","year":"2011","journal-title":"Proc Natl Acad Sci"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/mss279","article-title":"The adaptation of temperate bacteriophages to their host genomes","volume":"30","author":"Bobay","year":"2013","journal-title":"Mol Biol Evol"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgeb.2025.100510","article-title":"Reverse vaccinology and immunoinformatics approaches for multi-epitope vaccine design against Klebsiella pneumoniae reveal a novel vaccine target protein","volume":"23","author":"Elfadil","year":"2025","journal-title":"J Genet Eng Biotechnol"},{"key":"B116","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1038\/s41586-024-07487-w","article-title":"Accurate structure prediction of biomolecular interactions with AlphaFold 3","volume":"630","author":"Abramson","year":"2024","journal-title":"Nature"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.2510.15939","article-title":"Hallucinations in AlphaFold3 for Intrinsically Disordered Proteins with disorder in Biological Process Residues","author":"Gopalan","year":"2025","journal-title":"arXiv"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.2210\/pdb1hla\/pdb","article-title":"Structure of the human class I histocompatibility antigen, HLA-A2","volume":"329","author":"Bjorkman","year":"1987","journal-title":"Nature"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1007\/s002510050594","article-title":"Nine major HLA class I supertypes account for the vast preponderance of HLA-A and-B polymorphism","volume":"50","author":"Sette","year":"1999","journal-title":"Immunogenetics"},{"key":"B120","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2172-9-1","article-title":"HLA class I supertypes: a revised and updated classification","volume":"9","author":"Sidney","year":"2008","journal-title":"BMC Immunol"},{"key":"B121","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkaa379","article-title":"NetMHCpan-4.1 and NetMHCIIpan-4.0: improved predictions of MHC antigen presentation by concurrent motif deconvolution and integration of MS MHC eluted ligand data","volume":"48","author":"Reynisson","year":"2020","journal-title":"Nucleic Acids Res"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000107","article-title":"Quantitative predictions of peptide binding to any HLA-DR molecule of known sequence: NetMHCIIpan","volume":"4","author":"Nielsen","year":"2008","journal-title":"PloS Comput Biol"},{"key":"B123","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1146\/annurev.immunol.17.1.51","article-title":"Immunodominance in major histocompatibility complex class I\u2013restricted T lymphocyte responses","volume":"17","author":"Yewdell","year":"1999","journal-title":"Annu Rev Immunol"},{"key":"B124","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.coi.2021.04.009","article-title":"Major histocompatibility complex (MHC) class I and class II proteins: impact of polymorphism on antigen presentation","volume":"70","author":"Abualrous","year":"2021","journal-title":"Curr Opin Immunol"},{"key":"B125","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2013.04.003","article-title":"Follicular helper CD4 T cells (Tfh)","volume":"29","author":"Crotty","year":"2011","journal-title":"Annu Rev Immunol"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.11.1.729","article-title":"Dominance and crypticity of T cell antigenic determinants","volume":"11","author":"Sercarz","year":"1993","journal-title":"Annu Rev Immunol"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx346","article-title":"BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes","volume":"45","author":"Jespersen","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"B128","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3011.1997.tb00608.x","article-title":"Prediction of \u03b2\u2010turns","volume":"49","author":"Chou","year":"1997","journal-title":"J Pept Res"},{"key":"B129","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/0076-6879(91)03010-e","article-title":"8] Predicting location of continuous epitopes in proteins from their primary structures","volume":"203","author":"Pellequer","year":"1991","journal-title":"Methods Enzymol"},{"key":"B130","doi-asserted-by":"publisher","DOI":"10.1002\/jmr.893","article-title":"Predicting linear B\u2010cell epitopes using string kernels","volume":"21","author":"El\u2010Manzalawy","year":"2008","journal-title":"J Mol Recognition: Interdiscip J"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.6.3824","article-title":"Prediction of protein antigenic determinants from amino acid sequences","volume":"78","author":"Hopp","year":"1981","journal-title":"Proc Natl Acad Sci"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1021\/bi00367a013","article-title":"New hydrophilicity scale derived from high-performance liquid chromatography peptide retention data: correlation of predicted surface residues with antigenicity and X-ray-derived accessible sites","volume":"25","author":"Parker","year":"1986","journal-title":"Biochemistry"},{"key":"B133","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbi.2014.11.003","article-title":"An overview of bioinformatics tools for epitope prediction: implications on vaccine development","volume":"53","author":"Soria-Guerra","year":"2015","journal-title":"J BioMed Inf"},{"key":"B134","doi-asserted-by":"publisher","first-page":"64","DOI":"10.4016\/5328.01","article-title":"Antibody-protein interactions: benchmark datasets and prediction tools evaluation","volume":"7","author":"Ponomarenko","year":"2007","journal-title":"BMC Struct Biol"},{"key":"B135","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2023.1049917","article-title":"Non-antibiotic prevention and treatment against Acinetobacter baumannii infection: Are vaccines and adjuvants effective strategies","volume":"14","author":"Hu","year":"2023","journal-title":"Front Microbiol"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1128\/iai.00162-21","article-title":"Monoclonal antibody therapy against Acinetobacter baumannii","volume":"89","author":"Nielsen","year":"2021","journal-title":"Infect Immun"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20250025","article-title":"Chimeric MHC class I\u2013and II\u2013restricted non-self epitopes broaden antitumor T cell reactions","volume":"223","author":"Zhang","year":"2025","journal-title":"J Exp Med"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2015.10","article-title":"The multifaceted role of CD4+ T cells in CD8+ T cell memory","volume":"16","author":"Laidlaw","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2025.113044","article-title":"T cell epitope mapping reveals immunodominance of evolutionarily conserved regions within SARS-CoV-2 proteome","volume":"28","author":"Bozkus","year":"2025","journal-title":"Iscience"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008754","article-title":"Conservation and diversity of influenza A H1N1 HLA-restricted T cell epitope candidates for epitope-based vaccines","volume":"5","author":"Tan","year":"2010","journal-title":"PloS One"},{"key":"B141","doi-asserted-by":"publisher","first-page":"18203","DOI":"10.1038\/s41598-025-03246-7","article-title":"Genomic landscape of nosocomial Acinetobacter baumannii: A comprehensive analysis of the resistome, virulome, and mobilome","volume":"15","author":"Pearl","year":"2025","journal-title":"Sci Rep"},{"key":"B142","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2000.5197","article-title":"Automatic clustering of orthologs and in-paralogs from pairwise species comparisons","volume":"314","author":"Remm","year":"2001","journal-title":"J Mol Biol"},{"key":"B143","volume-title":"Blast","author":"Korf","year":"2003"},{"key":"B144","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1016\/0263-7855(90)80025-b","article-title":"Databases of homology-derived protein structures","volume":"8","author":"Sander","year":"1990","journal-title":"J Mol Graphics"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.01340-15","article-title":"Dark matter of the biosphere: the amazing world of bacteriophage diversity","volume":"89","author":"Hatfull","year":"2015","journal-title":"J Virol"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gky1006","article-title":"The immune epitope database (IEDB): 2018 update","volume":"47","author":"Vita","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku938","article-title":"The immune epitope database (IEDB) 3.0","volume":"43","author":"Vita","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.1110\/ps.0239403","article-title":"Reliable prediction of T\u2010cell epitopes using neural networks with novel sequence representations","volume":"12","author":"Nielsen","year":"2003","journal-title":"Protein Sci"},{"key":"B149","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae1092","article-title":"The immune epitope database (IEDB): 2024 update","volume":"53","author":"Vita","year":"2025","journal-title":"Nucleic Acids Res"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1835523\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T05:43:36Z","timestamp":1780551816000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1835523\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,4]]},"references-count":149,"alternative-id":["10.3389\/fimmu.2026.1835523"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1835523","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,4]]},"article-number":"1835523"}}