Grafting MSI-78A onto chitosan microspheres enhances its antimicrobial activity

• Tipo: Artigo em Revista Científica Internacional
• Data: 2022

Autores

Fonseca, DR (Autor) Outra; Moura, A (Autor) Outra; Leiro, V (Autor) Outra; Silva Carvalho, R (Autor) Outra; Berta Nogueiro Estevinho (Autor) FEUP; Seabra, CL (Autor) Outra; Henriques, PC (Autor) Outra; Lucena, M (Autor) Outra; Teixeira, C (Autor) Outra; Paula Gomes (Autor) FCUP; Parreira, P (Autor) Outra; Martins, MCL (Autor) Outra

Revista

Título: Acta Biomaterialia

Vol. 137

Páginas: 186-198

ISSN: 1742-7061

Editora: Elsevier

Indexação

ISI Web of Knowledge - 9 Citações

Scopus - 7 Citações

Outras Informações

ID Authenticus: P-00V-H90

DOI: 10.1016/j.actbio.2021.09.063

Abstract (EN): MSI-78A (Pexiganan A) is one of the few antimicrobial peptides (AMPs) able to kill Helicobacter pylori, a pathogenic bacterium that colonizes the gastric mucosa of half of the world's population. Antibiotics fail in 20-40% of H. pylori-infected patients, reinforcing the need for alternative treatments. Herein, a bioengineered approach was developed. MSI-78A with a C-terminal cysteine was grafted onto chitosan microspheres (AMP-ChMic) by thiol-maleimide (Michael-addition) chemistry using a long heterobifunctional spacer (NHS-PEG(113)-MAL). Microspheres with similar to 4 mu m diameter (near H. pylori length) and stable at low pH were produced by spray drying using a chitosan solution with an incomplete genipin crosslinking. A 3 x 10(-5) mu g AMP/microsphere grafting was estimated/confirmed by UV/Vis and FTIR spectroscopies. AMP-ChMic were bactericidal against H. pylori J99 (highly pathogenic human strain) at lower concentrations than the free peptide (similar to 277 mu g grafted MSI-78A-SH/mL vs 512 mu g free MSI-78A-SH/mL), even after pre-incubation in simulated gastric conditions with pepsin. AMP-ChMic killed H. pylori by membrane destabilization and cytoplasm release in a ratio of similar to 10 bacteria/microsphere. This can be attributed to H. pylori attraction to chitosan, facilitating the interaction of grafted AMP with bacterium membrane. Overall, it was demonstrated that the peptide-microsphere conjugation chemistry did not compromise the MSI-78A antimicrobial activity, instead it boosted its bactericidal performance against H. pylori. Statement of significance Half of the world's population is infected with Helicobacter pylori, a gastric bacterium that is responsible for 90% of non-cardia gastric cancers. Therefore, H. pylori eradication is now advocated in all infected individuals. However, available antibiotic therapies fail in up to 40% patients. Antimicrobial peptides (AMPs) are appealing alternatives to antibiotics, but their high susceptibility in vivo limits their clinical translation. AMP immobilization onto biomaterials surface will overcome this problem. Herein, we demonstrate that immobilization of MSI-78A (one of the few AMPs with activity against H. pylori) onto chitosan microspheres (AMP-ChMic) enhances its anti-H. pylori activity even at acidic pH (gastric settings). These results highlight the strong potential of AMP-ChMic as an antibiotic alternative for H. pylori eradication.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 13