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Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics. In this review, the in vitro\/in vivo activities of the frog skin-derived AMP Esc(1-21) are shown. Esc(1-21) rapidly kills both the planktonic and sessile forms of P. aeruginosa and stimulates migration of epithelial cells, likely favoring repair of damaged tissue. However, to undertake preclinical studies, some drawbacks of AMPs (cytotoxicity, poor biostability, and limited delivery to the target site) must be overcome. For this purpose, the stereochemistry of two amino acids of Esc(1-21) was changed to obtain the diastereomer Esc(1-21)-1c, which is more stable, less cytotoxic, and more efficient in treating P. aeruginosa-induced lung and cornea infections in mouse models. Incorporation of these peptides (Esc peptides) into nanoparticles or immobilization to a medical device (contact lens) was revealed to be an effective strategy to ameliorate and\/or to prolong the peptides\u2019 antimicrobial efficacy. Overall, these data make Esc peptides encouraging candidates for novel multifunctional drugs to treat lung pathology especially in patients with cystic fibrosis and eye dysfunctions, characterized by both tissue injury and bacterial infection.<\/jats:p>","DOI":"10.3390\/ijms25084400","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T08:22:44Z","timestamp":1713342164000},"page":"4400","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["An Overview of Frog Skin-Derived Esc Peptides: Promising Multifunctional Weapons against Pseudomonas aeruginosa-Induced Pulmonary and Ocular Surface Infections"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5991-5868","authenticated-orcid":false,"given":"Maria Luisa","family":"Mangoni","sequence":"first","affiliation":[{"name":"Laboratory Affiliated to Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5040-5688","authenticated-orcid":false,"given":"Maria Rosa","family":"Loffredo","sequence":"additional","affiliation":[{"name":"Laboratory Affiliated to Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1295-1084","authenticated-orcid":false,"given":"Bruno","family":"Casciaro","sequence":"additional","affiliation":[{"name":"Laboratory Affiliated to Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loretta","family":"Ferrera","sequence":"additional","affiliation":[{"name":"UOC Genetica Medica, IRCCS Istituto Giannina Gaslini, 16147 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3423-8474","authenticated-orcid":false,"given":"Floriana","family":"Cappiello","sequence":"additional","affiliation":[{"name":"Laboratory Affiliated to Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"ref_1","unstructured":"Antimicrobial Resistance Collaborators (2022). Global burden of bacterial antimicrobial resistance in 2019: A systematic analysis. Lancet, 399, 629\u2013655."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15190\/d.2018.1","article-title":"New FDA approved antibacterial drugs: 2015\u20132017","volume":"6","author":"Andrei","year":"2018","journal-title":"Discoveries"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13756-019-0662-8","article-title":"European intensive care physicians\u2019 experience of infections due to antibiotic-resistant bacteria","volume":"9","author":"Lepape","year":"2020","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Tang, K.W.K., Millar, B.C., and Moore, J.E. (2023). Antimicrobial Resistance (AMR). Br. J. Biomed. Sci., 80.","DOI":"10.3389\/bjbs.2023.11387"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Urban-Chmiel, R., Marek, A., Stepien-Pysniak, D., Wieczorek, K., Dec, M., Nowaczek, A., and Osek, J. (2022). Antibiotic Resistance in Bacteria-A Review. Antibiotics, 11.","DOI":"10.3390\/antibiotics11081079"},{"key":"ref_6","first-page":"A244","article-title":"The landscape of antibiotic resistance","volume":"117","year":"2009","journal-title":"Environ. Health Perspect."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1016\/S0140-6736(22)00087-3","article-title":"The overlooked pandemic of antimicrobial resistance","volume":"399","author":"Laxminarayan","year":"2022","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1086\/595011","article-title":"Bad bugs, no drugs: No ESKAPE! An update from the Infectious Diseases Society of America","volume":"48","author":"Boucher","year":"2009","journal-title":"Clin. Infect. Dis. Off. Publ. Infect. Dis. Soc. Am."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2201","DOI":"10.2147\/IDR.S306688","article-title":"Characterisation of ESKAPE Pathogens with Special Reference to Multidrug Resistance and Biofilm Production in a Nepalese Hospital","volume":"14","author":"Pandey","year":"2021","journal-title":"Infect. Drug Resist."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1007\/s40121-022-00591-2","article-title":"Therapeutic Strategies for Emerging Multidrug-Resistant Pseudomonas aeruginosa","volume":"11","author":"Holger","year":"2022","journal-title":"Infect. Dis. Ther."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1128\/JB.184.11.3027-3033.2002","article-title":"Pseudomonas aeruginosa virulence analyzed in a Dictyostelium discoideum host system","volume":"184","author":"Cosson","year":"2002","journal-title":"J. Bacteriol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Liao, C., Huang, X., Wang, Q., Yao, D., and Lu, W. (2022). Virulence Factors of Pseudomonas Aeruginosa and Antivirulence Strategies to Combat Its Drug Resistance. Front. Cell. Infect. Microbiol., 12.","DOI":"10.3389\/fcimb.2022.926758"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Thi, M.T.T., Wibowo, D., and Rehm, B.H.A. (2020). Pseudomonas aeruginosa Biofilms. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21228671"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Tuon, F.F., Dantas, L.R., Suss, P.H., and Tasca Ribeiro, V.S. (2022). Pathogenesis of the Pseudomonas aeruginosa Biofilm: A Review. Pathogens, 11.","DOI":"10.3390\/pathogens11030300"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s40496-014-0044-5","article-title":"The Biofilm Community-Rebels with a Cause","volume":"2","author":"Aruni","year":"2015","journal-title":"Curr. Oral Health Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13756-019-0533-3","article-title":"Antibiotics versus biofilm: An emerging battleground in microbial communities","volume":"8","author":"Sharma","year":"2019","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"53","DOI":"10.2174\/1874285801711010053","article-title":"Understanding the Mechanism of Bacterial Biofilms Resistance to Antimicrobial Agents","volume":"11","author":"Singh","year":"2017","journal-title":"Open Microbiol. J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1305294","DOI":"10.3389\/fphar.2023.1305294","article-title":"Antibiotic action and resistance: Updated review of mechanisms, spread, influencing factors, and alternative approaches for combating resistance","volume":"14","author":"Halawa","year":"2023","journal-title":"Front. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1099\/jmm.0.001110","article-title":"Pseudomonas aeruginosa and microbial keratitis","volume":"69","author":"Hilliam","year":"2020","journal-title":"J. Med. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e00138-18","DOI":"10.1128\/CMR.00138-18","article-title":"Cystic Fibrosis and Pseudomonas aeruginosa: The Host-Microbe Interface","volume":"32","author":"Malhotra","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1001\/jama.2023.8120","article-title":"Cystic Fibrosis: A Review","volume":"329","author":"Ong","year":"2023","journal-title":"JAMA"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Fukuda, R., and Okiyoneda, T. (2020). Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Ubiquitylation as a Novel Pharmaceutical Target for Cystic Fibrosis. Pharmaceuticals, 13.","DOI":"10.3390\/ph13040075"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Almughem, F.A., Aldossary, A.M., Tawfik, E.A., Alomary, M.N., Alharbi, W.S., Alshahrani, M.Y., and Alshehri, A.A. (2020). Cystic Fibrosis: Overview of the Current Development Trends and Innovative Therapeutic Strategies. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12070616"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/s00018-021-04030-2","article-title":"Esc peptides as novel potentiators of defective cystic fibrosis transmembrane conductance regulator: An unprecedented property of antimicrobial peptides","volume":"79","author":"Ferrera","year":"2021","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.molmed.2011.10.003","article-title":"CFTR: Folding, misfolding and correcting the DeltaF508 conformational defect","volume":"18","author":"Lukacs","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"102248","DOI":"10.1016\/j.coph.2022.102248","article-title":"Mucus-targeting therapies of defective mucus clearance for cystic fibrosis: A short review","volume":"65","author":"Figueira","year":"2022","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"543","DOI":"10.1111\/ceo.14113","article-title":"Infectious keratitis: A review","volume":"50","author":"Khoo","year":"2022","journal-title":"Clin. Exp. Ophthalmol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Somayajulu, M., McClellan, S.A., Muhammed, F., Wright, R., and Hazlett, L.D. (2023). PM(10) and Pseudomonas aeruginosa: Effects on corneal epithelium. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1240903"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Browne, K., Chakraborty, S., Chen, R., Willcox, M.D., Black, D.S., Walsh, W.R., and Kumar, N. (2020). A New Era of Antibiotics: The Clinical Potential of Antimicrobial Peptides. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21197047"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7820","DOI":"10.1039\/D0CS00729C","article-title":"The multifaceted nature of antimicrobial peptides: Current synthetic chemistry approaches and future directions","volume":"50","author":"Gan","year":"2021","journal-title":"Chem. Soc. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Rima, M., Rima, M., Fajloun, Z., Sabatier, J.M., Bechinger, B., and Naas, T. (2021). Antimicrobial Peptides: A Potent Alternative to Antibiotics. Antibiotics, 10.","DOI":"10.3390\/antibiotics10091095"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.it.2008.12.003","article-title":"AMPed up immunity: How antimicrobial peptides have multiple roles in immune defense","volume":"30","author":"Lai","year":"2009","journal-title":"Trends Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/s41573-019-0058-8","article-title":"Antimicrobial host defence peptides: Functions and clinical potential","volume":"19","author":"Mookherjee","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1146\/annurev.iy.13.040195.000425","article-title":"Peptide antibiotics and their role in innate immunity","volume":"13","author":"Boman","year":"1995","journal-title":"Annu. Rev. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1177\/0022034516679973","article-title":"Antimicrobial Peptides: Mechanisms of Action and Resistance","volume":"96","author":"Bechinger","year":"2017","journal-title":"J. Dent. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Agadi, N., Maity, A., Jha, A.K., Chakrabarti, R., and Kumar, A. (2022). Distinct mode of membrane interaction and disintegration by diverse class of antimicrobial peptides. Biochim. Biophys. Acta Biomembr., 1864.","DOI":"10.1016\/j.bbamem.2022.184047"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Luchini, A., and Vitiello, G. (2020). Mimicking the Mammalian Plasma Membrane: An Overview of Lipid Membrane Models for Biophysical Studies. Biomimetics, 6.","DOI":"10.3390\/biomimetics6010003"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1007\/978-981-13-3588-4_11","article-title":"Selectivity of Antimicrobial Peptides: A Complex Interplay of Multiple Equilibria","volume":"1117","author":"Bobone","year":"2019","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2174\/1568026615666150703121700","article-title":"Antimicrobial Peptide Structure and Mechanism of Action: A Focus on the Role of Membrane Structure","volume":"16","author":"Lee","year":"2016","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"105681","DOI":"10.1016\/j.envint.2020.105681","article-title":"The role of stereochemistry of antibiotic agents in the development of antibiotic resistance in the environment","volume":"139","author":"Elder","year":"2020","journal-title":"Environ. Int."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"300","DOI":"10.4103\/joacp.JOACP_349_15","article-title":"Action and resistance mechanisms of antibiotics: A guide for clinicians","volume":"33","author":"Kapoor","year":"2017","journal-title":"J. Anaesthesiol. Clin. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.1128\/AAC.00534-10","article-title":"New antiseptic peptides to protect against endotoxin-mediated shock","volume":"54","author":"Gutsmann","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Jang, M., Kim, J., Choi, Y., Bang, J., and Kim, Y. (2019). Antiseptic Effect of Ps-K18: Mechanism of Its Antibacterial and Anti-Inflammatory Activities. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20194895"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"149","DOI":"10.3389\/fimmu.2012.00149","article-title":"Multiple immune-modulatory functions of cathelicidin host defense peptides","volume":"3","author":"Choi","year":"2012","journal-title":"Front. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.pharmthera.2017.04.002","article-title":"Antimicrobial peptides: Role in human disease and potential as immunotherapies","volume":"178","author":"Silva","year":"2017","journal-title":"Pharmacol. Ther."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1248\/bpb.b22-00098","article-title":"The Antimicrobial Peptide Esculentin-1a(1-21)NH(2) Stimulates Wound Healing by Promoting Angiogenesis through the PI3K\/AKT Pathway","volume":"46","author":"Hu","year":"2022","journal-title":"Biol. Pharm. Bull."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1111\/j.1749-6632.2008.03618.x","article-title":"Dermal cytolytic peptides and the system of innate immunity in anurans","volume":"1163","author":"Conlon","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1007\/s00018-005-5536-y","article-title":"Temporins, anti-infective peptides with expanding properties","volume":"63","author":"Mangoni","year":"2006","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1089\/sur.2019.266","article-title":"Temporins: An Approach of Potential Pharmaceutic Candidates","volume":"21","author":"Romero","year":"2020","journal-title":"Surg. Infect."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1002\/(SICI)1097-0282(1998)47:6<435::AID-BIP3>3.0.CO;2-8","article-title":"Antimicrobial peptides from amphibian skin: What do they tell us?","volume":"47","author":"Simmaco","year":"1998","journal-title":"Biopolymers"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1007\/s00018-013-1291-7","article-title":"Esculentin(1-21), an amphibian skin membrane-active peptide with potent activity on both planktonic and biofilm cells of the bacterial pathogen Pseudomonas aeruginosa","volume":"70","author":"Luca","year":"2013","journal-title":"Cell. Mol. Life Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"2327","DOI":"10.1016\/j.bbamem.2017.09.009","article-title":"Membrane perturbing activities and structural properties of the frog-skin derived peptide Esculentin-1a(1-21)NH(2) and its Diastereomer Esc(1-21)-1c: Correlation with their antipseudomonal and cytotoxic activity","volume":"1859","author":"Loffredo","year":"2017","journal-title":"Biochim. Biophys. Acta Biomembr."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8548","DOI":"10.1038\/s41598-017-08361-8","article-title":"In vivo therapeutic efficacy of frog skin-derived peptides against Pseudomonas aeruginosa-induced pulmonary infection","volume":"7","author":"Chen","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3981","DOI":"10.1128\/IAI.00402-10","article-title":"Immune defenses against Batrachochytrium dendrobatidis, a fungus linked to global amphibian declines, in the South African clawed frog, Xenopus laevis","volume":"78","author":"Ramsey","year":"2010","journal-title":"Infect. Immun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1128\/CMR.00056-05","article-title":"Peptide antimicrobial agents","volume":"19","author":"Jenssen","year":"2006","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"43824","DOI":"10.1074\/jbc.M108842200","article-title":"Structure of DNA polymerase delta from Saccharomyces cerevisiae","volume":"276","author":"Johansson","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"7252","DOI":"10.1128\/AAC.00904-16","article-title":"Esculentin-1a-Derived Peptides Promote Clearance of Pseudomonas aeruginosa Internalized in Bronchial Cells of Cystic Fibrosis Patients and Lung Cell Migration: Biochemical Properties and a Plausible Mode of Action","volume":"60","author":"Cappiello","year":"2016","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_58","first-page":"155","article-title":"Pathophysiology of Lung Disease and Wound Repair in Cystic Fibrosis","volume":"28","author":"Conese","year":"2021","journal-title":"Pathophysiol. Off. J. Int. Soc. Pathophysiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3892\/etm.2011.402","article-title":"Influence of interleukin-8 (IL-8) and IL-8 receptors on the migration of human keratinocytes, the role of PLC-gamma and potential clinical implications","volume":"3","author":"Jiang","year":"2012","journal-title":"Exp. Ther. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/sj.jid.5701043","article-title":"In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37","volume":"128","author":"Carretero","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"18988","DOI":"10.1038\/s41598-019-55426-x","article-title":"Bronchial epithelium repair by Esculentin-1a-derived antimicrobial peptides: Involvement of metalloproteinase-9 and interleukin-8, and evaluation of peptides\u2019 immunogenicity","volume":"9","author":"Cappiello","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"562","DOI":"10.1021\/acsinfecdis.3c00491","article-title":"Mechanism of Protease Resistance of D-Amino Acid Residue Containing Cationic Antimicrobial Heptapeptides","volume":"10","author":"Sarkar","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1775","DOI":"10.1016\/S0006-2952(99)00259-2","article-title":"Effect of D-amino acid substitution on the stability, the secondary structure, and the activity of membrane-active peptide","volume":"58","author":"Hong","year":"1999","journal-title":"Biochem. Pharmacol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2505","DOI":"10.1007\/s00726-015-2041-y","article-title":"D-Amino acids incorporation in the frog skin-derived peptide esculentin-1a(1-21)NH2 is beneficial for its multiple functions","volume":"47","author":"Cappiello","year":"2015","journal-title":"Amino Acids"},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Ramirez-Larrota, J.S., and Eckhard, U. (2022). An Introduction to Bacterial Biofilms and Their Proteases, and Their Roles in Host Infection and Immune Evasion. Biomolecules, 12.","DOI":"10.3390\/biom12020306"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3874","DOI":"10.1111\/febs.14940","article-title":"Inhibition of Pseudomonas aeruginosa biofilm formation and expression of virulence genes by selective epimerization in the peptide Esculentin-1a(1-21)NH2","volume":"286","author":"Casciaro","year":"2019","journal-title":"FEBS J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1016\/j.ijmm.2009.08.017","article-title":"The synthesis and function of the alarmone (p)ppGpp in firmicutes","volume":"300","author":"Wolz","year":"2010","journal-title":"Int. J. Med. Microbiol. IJMM"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1271153","DOI":"10.3389\/fchem.2023.1271153","article-title":"The antimicrobial peptide Esc(1-21)-1c increases susceptibility of Pseudomonas aeruginosa to conventional antibiotics by decreasing the expression of the MexAB-OprM efflux pump","volume":"11","author":"Cane","year":"2023","journal-title":"Front. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"C888","DOI":"10.1152\/ajpcell.00313.2010","article-title":"CFTR channels and wound healing. Focus on \u201cCystic fibrosis transmembrane conductance regulator is involved in airway epithelial wound repair\u201d","volume":"299","author":"Kirk","year":"2010","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/0092-8674(91)90446-6","article-title":"Phosphorylation of the R domain by cAMP-dependent protein kinase regulates the CFTR chloride channel","volume":"66","author":"Cheng","year":"1991","journal-title":"Cell"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"S23","DOI":"10.1152\/physrev.1999.79.1.S23","article-title":"Structure and function of the CFTR chloride channel","volume":"79","author":"Sheppard","year":"1999","journal-title":"Physiol. Rev."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Sharma, J., Sharma, D., Singh, A., and Sunita, K. (2022). Colistin Resistance and Management of Drug Resistant Infections. Can. J. Infect. Dis. Med. Microbiol. J. Can. Des Mal. Infect. Microbiol. Medicale, 2022.","DOI":"10.1155\/2022\/4315030"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1007\/s40005-019-00456-w","article-title":"Poly(lactic acid)\/poly(lactic-co-glycolic acid) particulate carriers for pulmonary drug delivery","volume":"49","author":"Emami","year":"2019","journal-title":"J. Pharm. Investig."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"4136","DOI":"10.1021\/bm201226x","article-title":"Biodegradable nanoparticles meet the bronchial airway barrier: How surface properties affect their interaction with mucus and epithelial cells","volume":"12","author":"Mura","year":"2011","journal-title":"Biomacromolecules"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jconrel.2011.08.010","article-title":"Dry powders based on PLGA nanoparticles for pulmonary delivery of antibiotics: Modulation of encapsulation efficiency, release rate and lung deposition pattern by hydrophilic polymers","volume":"157","author":"Ungaro","year":"2012","journal-title":"J. Control. Release Off. J. Control. Release Soc."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Cresti, L., Conte, G., Cappello, G., Brunetti, J., Falciani, C., Bracci, L., Quaglia, F., Ungaro, F., d\u2019Angelo, I., and Pini, A. (2023). Inhalable Polymeric Nanoparticles for Pulmonary Delivery of Antimicrobial Peptide SET-M33: Antibacterial Activity and Toxicity In Vitro and In Vivo. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15010003"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1876","DOI":"10.1021\/acs.biomac.8b01829","article-title":"Poly(lactide- co-glycolide) Nanoparticles for Prolonged Therapeutic Efficacy of Esculentin-1a-Derived Antimicrobial Peptides against Pseudomonas aeruginosa Lung Infection: In Vitro and in Vivo Studies","volume":"20","author":"Casciaro","year":"2019","journal-title":"Biomacromolecules"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Cappiello, F., Casciaro, B., Loffredo, M.R., Puglisi, E., Lin, Q., Yang, D., Conte, G., d\u2019Angelo, I., Ungaro, F., and Ferrera, L. (2022). Pulmonary Safety Profile of Esc Peptides and Esc-Peptide-Loaded Poly(lactide-co-glycolide) Nanoparticles: A Promising Therapeutic Approach for Local Treatment of Lung Infectious Diseases. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14112297"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.jtos.2014.10.003","article-title":"Barrier function in the ocular surface: From conventional paradigms to new opportunities","volume":"13","author":"Leong","year":"2015","journal-title":"Ocul. Surf."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"100804","DOI":"10.1016\/j.preteyeres.2019.100804","article-title":"Contact lens-related corneal infection: Intrinsic resistance and its compromise","volume":"76","author":"Fleiszig","year":"2020","journal-title":"Prog. Retin. Eye Res."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1678","DOI":"10.1016\/j.ophtha.2017.05.012","article-title":"Update on the Management of Infectious Keratitis","volume":"124","author":"Austin","year":"2017","journal-title":"Ophthalmology"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"694998","DOI":"10.3389\/fchem.2021.694998","article-title":"Alternative Therapeutic Interventions: Antimicrobial Peptides and Small Molecules to Treat Microbial Keratitis","volume":"9","author":"Jadi","year":"2021","journal-title":"Front. Chem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1159\/000187622","article-title":"The role of antimicrobial peptides at the ocular surface","volume":"41","author":"McDermott","year":"2009","journal-title":"Ophthalmic Res."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"3795","DOI":"10.1167\/iovs.02-1301","article-title":"Expression of human beta-defensins in conjunctival epithelium: Relevance to dry eye disease","volume":"44","author":"Narayanan","year":"2003","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3853","DOI":"10.1128\/AAC.01317-06","article-title":"In vitro activity of human beta-defensin 2 against Pseudomonas aeruginosa in the presence of tear fluid","volume":"51","author":"Huang","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Cappiello, F., Verma, S., Lin, X., Moreno, I.Y., Casciaro, B., Dutta, D., McDermott, A.M., Willcox, M., Coulson-Thomas, V.J., and Mangoni, M.L. (2023). Novel Peptides with Dual Properties for Treating Pseudomonas aeruginosa Keratitis: Antibacterial and Corneal Wound Healing. Biomolecules, 13.","DOI":"10.3390\/biom13071028"},{"key":"ref_87","first-page":"101","article-title":"Effect of hybrid peptides of cecropin A and melittin in an experimental model of bacterial keratitis","volume":"16","author":"Portoles","year":"1997","journal-title":"Cornea"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"108089","DOI":"10.1016\/j.exer.2020.108089","article-title":"Corneal wound healing","volume":"197","author":"Wilson","year":"2020","journal-title":"Exp. Eye Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"8549","DOI":"10.1167\/iovs.11-7956","article-title":"Role of the IL-6 classic- and trans-signaling pathways in corneal sterile inflammation and wound healing","volume":"52","author":"Ebihara","year":"2011","journal-title":"Investig. Ophthalmol. Vis. Sci."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1016\/j.ophtha.2005.09.014","article-title":"The incidence of microbial keratitis among wearers of a 30-day silicone hydrogel extended-wear contact lens","volume":"112","author":"Schein","year":"2005","journal-title":"Ophthalmology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1076\/ceyr.17.3.257.5213","article-title":"Tear fluid content of electrochemically active components including water soluble antioxidants","volume":"17","author":"Gogia","year":"1998","journal-title":"Curr. Eye Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1268","DOI":"10.3390\/biology2041268","article-title":"A laboratory assessment of factors that affect bacterial adhesion to contact lenses","volume":"2","author":"Dutta","year":"2013","journal-title":"Biology"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"e23074","DOI":"10.1002\/bip.23074","article-title":"Esculentin-1a derived peptides kill Pseudomonas aeruginosa biofilm on soft contact lenses and retain antibacterial activity upon immobilization to the lens surface","volume":"110","author":"Casciaro","year":"2018","journal-title":"Pept. Sci."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"e24122","DOI":"10.1002\/pep2.24122","article-title":"Antimicrobial peptides under clinical investigation","volume":"111","author":"Koo","year":"2019","journal-title":"Pept. Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/j.addr.2020.12.016","article-title":"Recent advances in design of antimicrobial peptides and polypeptides toward clinical translation","volume":"170","author":"Jiang","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1080\/07388551.2020.1796576","article-title":"Antimicrobial peptides as therapeutic agents: Opportunities and challenges","volume":"40","author":"Mahlapuu","year":"2020","journal-title":"Crit. Rev. Biotechnol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4400\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:28:58Z","timestamp":1760106538000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/8\/4400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,16]]},"references-count":96,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25084400"],"URL":"https:\/\/doi.org\/10.3390\/ijms25084400","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,16]]}}}