{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T01:31:51Z","timestamp":1790299911419,"version":"4.1.0"},"reference-count":266,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T00:00:00Z","timestamp":1766534400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>The global incidence of multidrug-resistant (MDR) ESKAPE pathogens\u2014comprising Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species\u2014has surged alarmingly in recent years, posing a significant challenge to healthcare systems worldwide. These organisms are notorious for their capacity to evade the effects of multiple classes of antibiotics, leading to treatment failures, increased morbidity and mortality, and escalating healthcare costs, all of which have placed unprecedented strain on existing infection control measures. This review encapsulates the progress in target-driven vaccine research, including the genomic discovery of highly conserved surface antigens, iron acquisition systems, biofilm- and quorum-sensing-related proteins, and computationally predicted epitopes, which are considered the most attractive targets for broad-spectrum vaccination. Novel vaccine platforms, such as outer membrane vesicles (OMVs), mRNA technologies, and multi-epitope constructs, will rapidly drive the translation of these targets into next-generation vaccine formulations. Nevertheless, challenges such as antigenic variation and immune evasion, as well as the need for a robust mucosal and cross-protective immune response, persist. The sustainability in interdisciplinary investigations are required, along with adjunctive measures and investment in the development of advanced discovery and delivery systems, to achieve the ultimate goal of successful vaccines against MDR ESKAPE infections and to mitigate the worldwide burden of antimicrobial resistance.<\/jats:p>","DOI":"10.3390\/pathogens15010028","type":"journal-article","created":{"date-parts":[[2025,12,24]],"date-time":"2025-12-24T12:22:27Z","timestamp":1766578947000},"page":"28","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Taming Superbugs: Current Progress and Challenges in Combating ESKAPE Pathogens"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8541-7304","authenticated-orcid":false,"given":"Helal F.","family":"Hetta","sequence":"first","affiliation":[{"name":"Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma R.","family":"Khalaf","sequence":"additional","affiliation":[{"name":"Primary Health Care Department, Faculty of Nursing, Al-Ahliyya Amman University, Amman 19111, Jordan"},{"name":"Family and Community Health Nursing Department, Faculty of Nursing, Assiut University, Asyut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3368-3994","authenticated-orcid":false,"given":"Ahmed A.","family":"Kotb","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1788-4889","authenticated-orcid":false,"given":"Marah N.","family":"Alatawi","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8967-9875","authenticated-orcid":false,"given":"Abdullah S.","family":"Albalawi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1100-4771","authenticated-orcid":false,"given":"Ahmad A.","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Division of Microbiology, Immunology and Biotechnology, Department of Natural Products and Alternative Medicine, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam K.","family":"Aljohani","sequence":"additional","affiliation":[{"name":"PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shumukh Saad","family":"Aljohani","sequence":"additional","affiliation":[{"name":"PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majd S.","family":"Alatawi","sequence":"additional","affiliation":[{"name":"PharmD Program, Faculty of Pharmacy, University of Tabuk, Tabuk 71491, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noura H.","family":"Abd Ellah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Basem","family":"Battah","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Faculty of Pharmacy, Antioch Syrian Private University, Maaret Siadnaya 36822, Syria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7681-6194","authenticated-orcid":false,"given":"Matthew G.","family":"Donadu","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy, Giovanni Paolo II Hospital, ASL Gallura, 07026 Olbia, Italy"},{"name":"Department of Medicine, Surgery and Pharmacy, Scuola di Specializzazione in Farmacia Ospedaliera, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9713-3306","authenticated-orcid":false,"given":"Vittorio","family":"Mazzarello","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,24]]},"reference":[{"key":"ref_1","unstructured":"WHO (2025, February 19). 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