Efficacy of Cathelicidin LL-37 in an MRSA Wound Infection Mouse Model
Abstract
:1. Introduction
2. Results
2.1. Cytotoxicity Assay
2.2. Quantitative Cultures of Excised Tissues
2.3. Evaluation of Excised Samples by Histology
3. Discussion
4. Materials and Methods
4.1. Reagents
4.2. Bacterial Strains and Drugs
4.3. Ethics
4.4. Animals
4.5. Cytotoxicity Assay
4.5.1. Histology
4.5.2. Angiogenesis Evaluation
4.6. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Urbán, E.; Stone, G.G. Impact of EUCAST ceftaroline breakpoint change on the susceptibility of methicillin-resistant Staphylococcus aureus isolates collected from patients with complicated skin and soft-tissue infections. Clin. Microbiol. Infect. 2019, 25, 1429.e1–1429.e4. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sánchez-García, M.; Hammond, J.; Yan, J.L.; Kantecki, M.; Ansari, W.; Dryden, M. Baseline Characteristics and Outcomes Among Patients with Complicated Skin and Soft Tissue Infections Admitted to the Intensive Care Unit: Analysis of the Phase 3 COVERS Randomized Trial of Ceftaroline Fosamil Versus Vancomycin Plus Aztreonam. Infect. Dis. Ther. 2020, 9, 609–623. [Google Scholar] [CrossRef] [PubMed]
- Ramos-Martín, V.; Johnson, A.; McEntee, L.; Farrington, N.; Padmore, K.; Cojutti, P.; Pea, F.; Neely, M.N. Hope WW.Pharmacodynamics of teicoplanin against MRSA. J. Antimicrob. Chemother. 2017, 72, 3382–3389. [Google Scholar] [CrossRef]
- Chang, Q.; Wang, W.; Regev-Yochay, G.; Lipsitch, M.; Hanage, W.P. Antibiotics in agriculture and the risk to human health: How worried should we be? Evol. Appl. 2015, 8, 240–247. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ashwin, K.S.; Muralidharan, N.P. Vancomycin-resistant Enterococcus (VRE) vs methicillin-resistant Staphylococcus aureus (MRSA). Indian J. Med. Microbiol. 2015, 33, 166–167. [Google Scholar] [CrossRef]
- Mühlberg, E.; Umstätter, F.; Kleist, C.; Domhan, C.; Mier, W.; Uhl, P. Renaissance of vancomycin: Approaches for breaking antibiotic resistance in multidrug-resistant bacteria. Can. J. Microbiol. 2020, 66, 11–16. [Google Scholar] [CrossRef] [Green Version]
- Bakthavatchalam, Y.D.; Babu, P.; Munusamy, E.; Dwarakanathan, H.T.; Rupali, P.; Zervos, M.; John Victor, P.; Veeraraghavan, B. Genomic insights on heterogeneous resistance to vancomycin and teicoplanin in Methicillin-resistant Staphylococcus aureus: A first report from South India. PLoS ONE 2019, 14, e0227009. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kamysz, E.; Simonetti, O.; Cirioni, O.; Arzeni, D.; Ganzetti, G.; Campanati, A.; Giacometti, A.; Gabrielli, E.; Silvestri, C.; Kamysz, W.; et al. In vitro activity of the lipopeptide PAL-Lys-Lys-NH2, alone and in combination with antifungal agents, against clinical isolates of Candida spp. Peptides 2011, 32, 99–103. [Google Scholar] [CrossRef] [PubMed]
- Barchiesi, F.; Silvestri, C.; Arzeni, D.; Ganzetti, G.; Castelletti, S.; Simonetti, O.; Cirioni, O.; Kamysz, W.; Kamysz, E.; Spreghini, E.; et al. In vitro susceptibility of dermatophytes to conventional and alternative antifungal agents. Med. Mycol. 2009, 47, 321–326. [Google Scholar] [CrossRef] [Green Version]
- Simonetti, O.; Cirioni, O.; Cacciatore, I.; Baldassarre, L.; Orlando, F.; Pierpaoli, E.; Lucarini, G.; Orsetti, E.; Provinciali, M.; Fornasari, E.; et al. Efficacy of the Quorum Sensing Inhibitor FS10 Alone and in Combination with Tigecycline in an Animal Model of Staphylococcal Infected Wound. PLoS ONE 2016, 11, e0151956. [Google Scholar] [CrossRef] [PubMed]
- Dijksteel, G.S.; Ulrich, M.M.W.; Middelkoop, E.; Boekema, B.K.H.L. Review: Lessons Learned From Clinical Trials Using Antimicrobial Peptides (AMPs). Front. Microbiol. 2021, 22, 12:616979. [Google Scholar] [CrossRef]
- Lazzaro, B.P.; Zasloff, M.; Rolff, J. Antimicrobial peptides: Application informed by evolution. Science 2020, 368, aau5480. [Google Scholar] [CrossRef]
- Simonetti, O.; Arzeni, D.; Ganzetti, G.; Silvestri, C.; Cirioni, O.; Gabrielli, E.; Castelletti, S.; Kamysz, W.; Kamysz, E.; Scalise, G.; et al. In vitro activity of the lipopeptide derivative (Pal-Lys-Lys-NH), alone and in combination with antifungal agents, against clinical isolates of dermatophytes. Br. J. Dermatol. 2009, 161, 249–252. [Google Scholar] [CrossRef] [PubMed]
- Simonetti, O.; Ganzetti, G.; Arzeni, D.; Campanati, A.; Marconi, B.; Silvestri, C.; Cirioni, O.; Gabrielli, E.; Lenci, I.; Kamysz, W.; et al. In vitro activity of Tachyplesin III alone and in combination with terbinafine against clinical isolates of dermatophytes. Peptides 2009, 30, 1794–1797. [Google Scholar] [CrossRef] [PubMed]
- Simonetti, O.; Cirioni, O.; Mocchegiani, F.; Cacciatore, I.; Silvestri, C.; Baldassarre, L.; Orlando, F.; Castelli, P.; Provinciali, M.; Vivarelli, M.; et al. The efficacy of the quorum sensing inhibitor FS8 and tigecycline in preventing prosthesis biofilm in an animal model of staphylococcal infection. Int. J. Mol. Sci. 2013, 14, 16321–16332. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Simonetti, O.; Cirioni, O.; Ghiselli, R.; Orlando, F.; Silvestri, C.; Mazzocato, S.; Kamysz, W.; Kamysz, E.; Provinciali, M.; Giacometti, A.; et al. In vitro activity and in vivo animal model efficacy of IB-367 alone and in combination with imipenem and colistin against Gram-negative bacteria. Peptides 2014, 55, 17–22. [Google Scholar] [CrossRef] [PubMed]
- Cirioni, O.; Simonetti, O.; Morroni, G.; Brescini, L.; Kamysz, W.; Kamysz, E.; Orlando, F.; Pierpaoli, E.; Caffarini, M.; Orciani, M.; et al. Efficacy of Pexiganan Combination with Tigecycline in a Mouse Model of Pseudomonas aeruginosa Sepsis. Curr. Top. Med. Chem. 2018, 18, 2127–2132. [Google Scholar] [CrossRef] [PubMed]
- Morroni, G.; Simonetti, O.; Brenciani, A.; Brescini, L.; Kamysz, W.; Kamysz, E.; Neubauer, D.; Caffarini, M.; Orciani, M.; Giovanetti, E.; et al. In vitro activity of Protegrin-1, alone and in combination with clinically useful antibiotics, against Acinetobacter baumannii strains isolated from surgical wounds. Med. Microbiol. Immunol. 2019, 208, 877–883. [Google Scholar] [CrossRef]
- Wertz, P.W.; de Szalay, S. Antibiotics (Basel). Innate Antimicrobial Defense of Skin and Oral Mucosa. Antibiotics 2020, 9, 159. [Google Scholar] [CrossRef] [Green Version]
- Cowland, J.B.; Johnsen, A.H.; Borregaard, N. hCAP-18, a cathelin/pro-bactenecin-like protein of human neutrophil specific granules. FEBS Lett. 1995, 368, 173–176. [Google Scholar] [CrossRef] [Green Version]
- Xhindoli, D.; Pacor, S.; Benincasa, M.; Scocchi, M.; Gennaro, R.; Tossi, A. The human cathelicidin LL-37—A ore-forming antibacterial peptide and host-cell modulator. Biochim. Biophys. Acta 2016, 1858, 546–566. [Google Scholar] [CrossRef]
- Yin, L.M.; Edwards, M.A.; Li, J.; Yip, C.M.; Deber, C.M. Roles of hydrophobicity and charge distribution of cationic antimicrobial peptides in peptide-membrane interactions. J. Biol. Chem. 2012, 287, 7738–7745. [Google Scholar] [CrossRef] [Green Version]
- Ridyard, K.E.; Overhage, J. The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent. Antibiotics 2021, 10, 650. [Google Scholar] [CrossRef] [PubMed]
- Luo, X.L.; Li, J.X.; Huang, H.R.; Duan, J.L.; Dai, R.X.; Tao, R.J.; Yang, L.; Hou, J.Y.; Jia, X.M.; Xu, J.F. LL37 Inhibits Aspergillus fumigatus Infection via Directly Binding to the Fungus and Preventing Excessive Inflammation. Front. Immunol. 2019, 10, 283. [Google Scholar] [CrossRef] [PubMed]
- Tsai, P.W.; Cheng, Y.L.; Hsieh, W.P.; Lan, C.Y. Responses of Candida albicans to the human antimicrobial peptide LL-37. J. Microbiol. 2014, 52, 581–589. [Google Scholar] [CrossRef]
- Zanetti, M. Cathelicidins, multifunctional peptides of the innate immunity. J. Leukoc. Biol. 2004, 75, 39–48. [Google Scholar] [CrossRef] [PubMed]
- Yu, Y.; Cooper, C.L.; Wang, G.; Morwitzer, M.J.; Kota, K.; Tran, J.P.; Bradfute, S.B.; Liu, Y.; Shao, J.; Zhang, A.K.; et al. Engineered Human Cathelicidin Antimicrobial Peptides Inhibit Ebola Virus Infection. iScience 2020, 23, 100999. [Google Scholar] [CrossRef]
- Kahlenberg, J.M.; Kaplan, M.J. Little peptide, big effects: The role of LL-37 in inflammation and autoimmune disease. J. Immunol. 2013, 191, 4895–4901. [Google Scholar] [CrossRef] [Green Version]
- Heilborn, J.D.; Nilsson, M.F.; Kratz, G.; Weber, G.; Sørensen, O.; Borregaard, N.; Ståhle-Bäckdahl, M. The cathelicidin anti-microbial peptide LL-37 is involved in re-epithelialization of human skin wounds and is lacking in chronic ulcer epithelium. J. Investig. Dermatol. 2003, 120, 379–389. [Google Scholar] [CrossRef] [Green Version]
- Carretero, M.; Escámez, M.J.; García, M.; Duarte, B.; Holguín, A.; Retamosa, L.; Jorcano, J.L.; Río, M.D.; Larcher, F. In vitro and in vivo wound healing-promoting activities of human cathelicidin LL-37. J. Investig. Dermatol. 2008, 128, 223–236. [Google Scholar] [CrossRef] [Green Version]
- Salvado, M.D.; Di Gennaro, A.; Lindbom, L.; Agerberth, B.; Haeggström, J.Z. Cathelicidin LL-37 induces angiogenesis via PGE2-EP3 signaling in endothelial cells, in vivo inhibition by aspirin. Arterioscler. Thromb. Vasc. Biol. 2013, 33, 1965–1972. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lakhundi, S.; Zhang, K. Methicillin-Resistant Staphylococcus aureus: Molecular Characterization, Evolution, and Epidemiology. Clin. Microbiol. Rev. 2018, 31, e00020-18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mohamed, M.F.; Hamed, M.I.; Panitch, A.; Seleem, M.N. Targeting methicillin-resistant Staphylococcus aureus with short salt-resistant synthetic peptides. Antimicrob. Agents Chemother. 2014, 58, 4113–4122. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, S.; Xiong, Y.; Chen, J.; Ghanem, A.; Wang, Y.; Yang, J.; Sun, B. Three Dimensional Printing Bilayer Membrane Scaffold Promotes Wound Healing. Front. Bioeng. Biotechnol. 2019, 7, 348. [Google Scholar] [CrossRef]
- Wu, W.K.; Wong, C.C.; Li, Z.J.; Zhang, L.; Ren, S.X.; Cho, C.H. Cathelicidins in inflammation and tissue repair: Potential therapeutic applications for gastrointestinal disorders. Acta Pharmacol. Sin. 2010, 31, 1118–1122. [Google Scholar] [CrossRef]
- Yan, C.Y.; Liu, Y.Z.; Xu, Z.H.; Yang, H.Y.; Li, J. Comparison of Antibacterial Effect of Cationic Peptide LL-37 and Cefalexin on Clinical Staphylococcus aureus-induced Infection after Femur Fracture Fixation. Orthop. Surg. 2020, 12, 1313–1318. [Google Scholar] [CrossRef]
- Noore, J.; Noore, A.; Li, B. Cationic antimicrobial peptide LL-37 is effective against both extra- and intracellular Staphylococcus aureus. Antimicrob. Agents Chemother. 2013, 57, 1283–1290. [Google Scholar] [CrossRef] [Green Version]
- Barańska-Rybak, W.; Sonesson, A.; Nowicki, R.; Schmidtchen, A. Glycosaminoglycans inhibit the antibacterial activity of LL-37 in biological fluids. J. Antimicrob. Chemother. 2006, 57, 260–265. [Google Scholar] [CrossRef]
- Narayana, J.L.; Mishra, B.; Lushnikova, T.; Golla, R.M.; Wang, G. Modulation of antimicrobial potency of human cathelicidin peptides against the ESKAPE pathogens and in vivo efficacy in a murine catheter-associated biofilm model. Biochim. Biophys. Acta Biomembr. 2019, 1861, 1592–1602. [Google Scholar] [CrossRef]
- Blodkamp, S.; Kadlec, K.; Gutsmann, T.; Naim, H.Y.; von Köckritz-Blickwede, M.; Schwarz, S. In vitro activity of human and animal cathelicidins against livestock-associated methicillin-resistant Staphylococcus aureus. Vet. Microbiol. 2016, 194, 107–111. [Google Scholar] [CrossRef]
- Sun, Y.; Sun, T.L.; Huang, H.W. Mode of Action of Antimicrobial Peptides on E. coli Spheroplasts. Biophys. J. 2016, 111, 132–139. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Arcilla, M.S.; van Hattem, J.M.; Matamoros, S.; Melles, D.C.; Penders, J.; de Jong, M.D.; Schultsz, C.; COMBAT consortium. Dissemination of the mcr-1 colistin resistance gene. Lancet Infect. Dis. 2016, 16, 147–149. [Google Scholar] [CrossRef] [Green Version]
- Andersson, D.I.; Hughes, D.; Kubicek-Sutherland, J.Z. Mechanisms and consequences of bacterial resistance to antimicrobial peptides. Drug Resist. Updates 2016, 26, 43–57. [Google Scholar] [CrossRef] [PubMed]
- Pieters, R.J.; Arnusch, C.J.; Breukink, E. Membrane permeabilization by multivalent anti-microbial peptides. Protein Pept. Lett. 2009, 16, 736–742. [Google Scholar] [CrossRef]
- Nicias, P. Multifunctional host defense peptides: Intracellular-targeting antimicrobial peptides. FEBS J. 2009, 276, 6483–6496. [Google Scholar] [CrossRef]
- Chan, D.I.; Prenner, E.J.; Vogel, H.J. Tryptophan- and arginine-rich antimicrobial peptides: Structures and mechanisms of action. Biochim. Biophys. Acta 2006, 1758, 1184–1202. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mukhopadhyay, K.; Whitmire, W.; Xiong, Y.Q.; Molden, J.; Jones, T.; Peschel, A.; Staubitz, P.; Adler-Moore, J.; McNamara, P.J.; Proctor, R.A.; et al. In vitro susceptibility of Staphylococcus aureus to thrombin-induced platelet microbicidal protein-1 (tPMP-1) is influenced by cell membrane phospholipid composition and asymmetry. Microbiology 2007, 153, 1187–1197. [Google Scholar] [CrossRef] [Green Version]
- Thwaite, J.E.; Hibbs, S.; Titball, R.W.; Atkins, T.P. Proteolytic degradation of human antimicrobial peptide LL-37 by Bacillus anthracis may contribute to virulence. Antimicrob. Agents Chemother. 2006, 50, 2316–2322. [Google Scholar] [CrossRef] [Green Version]
- Tokumaru, S.; Sayama, K.; Shirakata, Y.; Komatsuzawa, H.; Ouhara, K.; Hanakawa, Y.; Yahata, Y.; Dai, X.; Tohyama, M.; Nagai, H.; et al. Induction of keratinocyte migration via transactivation of the epidermal growth factor receptor by the antimicrobial peptide LL-37. J. Immunol. 2005, 175, 4662–4668. [Google Scholar] [CrossRef] [Green Version]
- Simonetti, O.; Lucarini, G.; Orlando, F.; Pierpaoli, E.; Ghiselli, R.; Provinciali, M.; Castelli, P.; Guerrieri, M.; Di Primio, R.; Offidani, A.; et al. Role of Daptomycin on Burn Wound Healing in an Animal Methicillin-Resistant Staphylococcus aureus Infection Model. Antimicrob. Agents Chemother. 2017, 61, e00606-17. [Google Scholar] [CrossRef] [Green Version]
- Simonetti, O.; Lucarini, G.; Morroni, G.; Orlando, F.; Lazzarini, R.; Zizzi, A.; Brescini, L.; Provinciali, M.; Giacometti, A.; Offidani, A.; et al. New Evidence and Insights on Dalbavancin and Wound Healing in a Mouse Model of Skin Infection. Antimicrob. Agents Chemother. 2020, 64, e02062-19. [Google Scholar] [CrossRef]
- Singer, A.J.; Clark, R.A. Cutaneous wound healing. N. Engl. J. Med. 1999, 341, 738–746. [Google Scholar] [CrossRef] [PubMed]
- Gillitzer, R.; Goebeler, M. Chemokines in cutaneous wound healing. J. Leukoc. Biol. 2001, 69, 513–521. [Google Scholar]
- Ferrara, N. VEGF and Intraocular Neovascularization: From Discovery to Therapy. Transl. Vis. Sci. Technol. 2016, 5, 9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Apte, R.S.; Chen, D.S.; Ferrara, N. VEGF in Signaling and Disease: Beyond Discovery and Development. Cell 2019, 176, 1248–1264. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ferrara, N.; Adamis, A.P. Ten years of anti-vascular endothelial growth factor therapy. Nat. Rev. Drug Discov. 2016, 15, 385–403. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Simonetti, O.; Lucarini, G.; Rubini, C.; Lazzarini, R.; Di Primio, R.; Offidani, A. Clinical and prognostic significance of survivin, AKT and VEGF in primary mucosal oral melanoma. Anticancer Res. 2015, 35, 2113–2120. [Google Scholar] [PubMed]
- Lucarini, G.; Simonetti, O.; Lazzarini, R.; Giantomassi, F.; Goteri, G.; Offidani, A. Vascular endothelial growth factor/semaphorin-3A ratio and SEMA3A expression in cutaneous malignant melanoma. Melanoma Res. 2020, 30, 433–442. [Google Scholar] [CrossRef]
- Koczulla, R.; von Degenfeld, G.; Kupatt, C. An angiogenic role for the human peptide antibiotic LL-37/hCAP-18. J. Clin. Investig. 2003, 111, 1165–1172. [Google Scholar] [CrossRef] [PubMed]
- Kamysz, E.; Sikorska, E.; Karafova, A.; Dawgul, M. Synthesis, biological activity and conformational analysis of head-to-tail cyclic analogues of LL37 and histatin 5. J. Pept. Sci. 2012, 18, 560–566. [Google Scholar] [CrossRef]
- Makowska, J.; Wyrzykowski, D.; Kamysz, E.; Tesmar, A.; Kamysz, W.; Chmurzy´nski, L. Probing the binding selected metal ions and biologically active substances to the antimicrobial peptide LL-37 using DSC, ITC measurements and calculations. J. Therm. Anal. Calorim. 2019, 138, 4523–4529. [Google Scholar] [CrossRef] [Green Version]
- Silvestri, C.; Cirioni, O.; Arzeni, D.; Ghiselli, R.; Simonetti, O.; Orlando, F.; Ganzetti, G.; Staffolani, S.; Brescini, L.; Provinciali, M.; et al. In vitro activity and in vivo efficacy of tigecycline alone and in combination with daptomycin and rifampin against Gram-positive cocci isolated from surgical wound infection. Eur. J. Clin. Microbiol. Infect. Dis. 2012, 31, 1759–1764. [Google Scholar] [CrossRef] [PubMed]
- Cirioni, O.; Silvestri, C.; Pierpaoli, E.; Barucca, A.; Kamysz, W.; Ghiselli, R.; Scalise, A.; Brescini, L.; Castelli, P.; Orlando, F.; et al. IB-367 pre-treatment improves the in vivo efficacy of teicoplanin and daptomycin in an animal model of wounds infected with meticillin-resistant Staphylococcus aureus. J. Med. Microbiol. 2013, 62, 1552–1558. [Google Scholar] [CrossRef] [Green Version]
- Simonetti, O.; Cirioni, O.; Ghiselli, R.; Goteri, G.; Orlando, F.; Monfregola, L.; De Luca, S.; Zizzi, A.; Silvestri, C.; Veglia, G.; et al. Antimicrobial properties of distinctin in an experimental model of MRSA-infected wounds. Eur. J. Clin. Microbiol. Infect. Dis. 2012, 31, 3047–3055. [Google Scholar] [CrossRef] [PubMed]
Treatment | Re-Epithelialization | Granulation Tissue | Collagen Organization |
---|---|---|---|
C0 Uninfected and no treatment, control group | 2.67 ± 0.44 | 2.93 ± 0.87 | 2.57 ± 0.38 |
C1 Infected and no treatment, control group | 1.11 ± 0.51 | 2.04 ± 0.62 | 0.72 ± 0.35 |
C2 Infected and treated with topical teicoplanin | 2.48 ± 0.43 | 2.41 ± 0.69 | 2.09 ± 0.54 |
C3 Infected and treated with daily i.p. teicoplanin | 2.00 ± 0.49 | 2.19 ± 0.71 | 1.91 ± 0.66 |
C4 Infected and treated with topical teicoplanin and daily i.p. teicoplanin | 2.63 ± 0.67 | 2.85 ± 0.48 | 2.32 ± 0.60 |
C5 Infected and treated with topical LL37 | 2.54 ± 0.52 * | 2.81 ± 0.74 * | 2.49 ± 0.49 * |
C6 Infected and treated with daily i.p. LL37 | 2.38 ± 0.63 * | 2.42 ± 0.49 * | 2.16 ± 0.33 * |
C7 Infected and treated with topical LL37 and daily i.p. LL37 | 2.70 ± 0.52 * | 2.90 ± 0.74 * | 2.73 ± 0.49 * |
Treatment | MVD Expression (Small Vessels/mm2) | VEGF Expression (Positive Cells/mm2) |
---|---|---|
C0 Uninfected and no treatment, control group | 230.53 ± 30.21 | 467.52 ± 38.76 |
C1 Infected and no treatment, control group | 155.36 ± 33.68 | 294.27 ± 46.22 |
C2 Infected and treated with topical teicoplanin | 204.66 ± 49.76 | 359.86 ± 135.20 |
C3 Infected and treated with daily i.p. teicoplanin | 215.03 ± 66.48 | 373.78 ± 122.37 |
C4 Infected and treated with topical teicoplanin and daily i.p. teicoplanin | 226.59 ± 57.33 | 456.38 ± 45.78 |
C5 Infected and treated with topical LL37 | 265.63 ± 31.6 * | 470.82 ± 46.61 * |
C6 Infected and treated with daily i.p. LL37 | 227.52 ± 38.9 * | 459.24 ± 37.6 * |
C7 Infected and treated with topical LL37 and daily i.p. LL37 | 271.77 ± 54.9 * | 493.47 ± 68.18 * |
Score | Re-Epithelialization | Granulation Tissue Formation | Collagen Organization |
---|---|---|---|
0 | None | None | None |
1 | Migrating epithelial cells | Hypo cellular with few vessels | Trace |
2 | Partial stratum corneum | Many vessels and some cells | Slight |
3 | Hypertrophic stratum corneum | Many fibroblasts, some fibers | Moderate |
4 | Complete and normal stratum corneum | More fibers, few cells | Marked |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Simonetti, O.; Cirioni, O.; Goteri, G.; Lucarini, G.; Kamysz, E.; Kamysz, W.; Orlando, F.; Rizzetto, G.; Molinelli, E.; Morroni, G.; et al. Efficacy of Cathelicidin LL-37 in an MRSA Wound Infection Mouse Model. Antibiotics 2021, 10, 1210. https://doi.org/10.3390/antibiotics10101210
Simonetti O, Cirioni O, Goteri G, Lucarini G, Kamysz E, Kamysz W, Orlando F, Rizzetto G, Molinelli E, Morroni G, et al. Efficacy of Cathelicidin LL-37 in an MRSA Wound Infection Mouse Model. Antibiotics. 2021; 10(10):1210. https://doi.org/10.3390/antibiotics10101210
Chicago/Turabian StyleSimonetti, Oriana, Oscar Cirioni, Gaia Goteri, Guendalina Lucarini, Elżbieta Kamysz, Wojciech Kamysz, Fiorenza Orlando, Giulio Rizzetto, Elisa Molinelli, Gianluca Morroni, and et al. 2021. "Efficacy of Cathelicidin LL-37 in an MRSA Wound Infection Mouse Model" Antibiotics 10, no. 10: 1210. https://doi.org/10.3390/antibiotics10101210