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Peer-reviewedCC BYFuture Pharmacology

Antimicrobial Peptides Against ESKAPE Pathogens: Mechanisms, Molecular Optimization, and Current Limitations

  • Christian Shleider Carnero Canales1
  • Miguel D’Agostino dos Santos2
  • Ana Carolina Cerqueira Negri2
  • Luiza Rossi Gois2
  • Subham Kumar Vishwakarma2
  • Cesar Augusto Roque‐Borda2
  • Fernando Rogerio Pavan2
  1. 1School of Biotechnology Engineering, Universidad Católica de Santa María (UCSM), Arequipa 040101, Peru
  2. 2Tuberculosis Research Laboratory, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, Brazil
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Abstract

ESKAPE pathogens represent a priority clinical threat due to their multidrug-resistance, persistence in biofilms, and ability to evade antibiotic therapy. In response to these limitations, antimicrobial peptides (AMPs) have emerged as promising platforms for the development of novel anti-infective strategies. This review analyzes the potential of AMPs against ESKAPE pathogens, integrating their main classes, mechanisms of action, design strategies, and barriers to clinical translation. Natural, synthetic, and peptidomimetic AMPs are examined, along with lytic mechanisms, intracellular targets, anti-virulence effects, quorum quenching, and immunomodulation. In addition, in silico design approaches, multi-objective prediction, and molecular optimization strategies—including stereochemical modifications, cyclization, lipidation, PEGylation, and hybrid design—are discussed. Finally, their activity against ESKAPE biofilms is addressed, together with current limitations related to stability, toxicity, delivery, and preclinical validation.

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Cite

BibTeXRIS
BibTeX
@article{canales2026antimicrobial,
  title = {{Antimicrobial Peptides Against ESKAPE Pathogens: Mechanisms, Molecular Optimization, and Current Limitations}},
  author = {Christian Shleider Carnero Canales and Miguel D’Agostino dos Santos and Ana Carolina Cerqueira Negri and Luiza Rossi Gois and Subham Kumar Vishwakarma and Cesar Augusto Roque‐Borda and Fernando Rogerio Pavan},
  journal = {Future Pharmacology},
  year = {2026},
  month = jun,
  doi = {10.3390/futurepharmacol6020032},
  url = {https://doi.org/10.3390/futurepharmacol6020032},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Antimicrobial Peptides Against ESKAPE Pathogens: Mechanisms, Molecular Optimization, and Current Limitations
AU  - Christian Shleider Carnero Canales
AU  - Miguel D’Agostino dos Santos
AU  - Ana Carolina Cerqueira Negri
AU  - Luiza Rossi Gois
AU  - Subham Kumar Vishwakarma
AU  - Cesar Augusto Roque‐Borda
AU  - Fernando Rogerio Pavan
PY  - 2026
DA  - 2026/06/16
JO  - Future Pharmacology
DO  - 10.3390/futurepharmacol6020032
UR  - https://doi.org/10.3390/futurepharmacol6020032
AB  - ESKAPE pathogens represent a priority clinical threat due to their multidrug-resistance, persistence in biofilms, and ability to evade antibiotic therapy. In response to these limitations, antimicrobial peptides (AMPs) have emerged as promising platforms for the development of novel anti-infective strategies. This review analyzes the potential of AMPs against ESKAPE pathogens, integrating their main classes, mechanisms of action, design strategies, and barriers to clinical translation. Natural, synthetic, and peptidomimetic AMPs are examined, along with lytic mechanisms, intracellular targets, anti-virulence effects, quorum quenching, and immunomodulation. In addition, in silico design approaches, multi-objective prediction, and molecular optimization strategies—including stereochemical modifications, cyclization, lipidation, PEGylation, and hybrid design—are discussed. Finally, their activity against ESKAPE biofilms is addressed, together with current limitations related to stability, toxicity, delivery, and preclinical validation.
SN  - 2673-9879
ER  -