Con la diffusione di sempre più ceppi batterici resistenti agli antibiotici, la ricerca si sta muovendo da tempo verso nuovi potenziali armi per combattere queste pericolosissime infezioni batteriche.
L’impiego di antibiotici è estremamente importante per
combattere le infezioni causate dai batteri, trattando efficacemente malattie gravi, anche mortali. Negli ultimi decenni però, il loro utilizzo, inappropriato ed eccessivo, in medicina umana, veterinaria e in agricoltura ha portato allo sviluppo di microrganismi resistenti ai farmaci e ad un rapido aumento della loro frequenza.
L’antibiotico-resistenza, sta diventando un grave problema sempre più sentito in ambiente sanitario. La maggior parte dei ceppi batterici è resistente ad un gran numero di agenti antimicrobici di uso più comune, come i macrolidi, gli amminoglicosidi e le cefalosporine di ultima generazione. Per questo la ricerca sui peptidi antimicrobici è davvero importante.
I peptidi antimicrobici (Antimicrobial Peptides, AMPs) sono delle piccole molecole proteiche costituite da 12-50 aminoacidi largamente diffuse in natura.
Peptidi con attività biologica sono stati infatti isolati da un elevato numero di organismi, quali batteri, piante, insetti, anfibi e mammiferi.
I primi peptidi ad essere studiati sono stati le cecropine, isolate nel baco da seta (Hyalophora cecropia) agli inizi degli anni ’80 e la melittina, isolata dal veleno dell’ape da miele (Apis mellifera). Quest’ultima è uno dei peptidi studiati più a fondo e per questo motivo è utilizzata spesso come riferimento per lo studio di nuove molecole.
Gli AMPs svolgono un ruolo molto importante nella cosiddetta immunità innata, costituita da una serie di meccanismi di difesa non specifici, diretti verso un largo spettro di microrganismi e presenti in un individuo fin dalla nascita. Questi rappresentano la prima vera barriera di difesa dell’organismo agli agenti patogeni.
Il meccanismo d’azione degli AMPs è riconducibile all’alterazione della membrane cellulari delle cellule bersaglio a seguito della interazione tra il peptide, carico positivamente, e le strutture di membrana dotate di carica netta negativa.
Gli effetti che possono conseguire a tale interazione sono:
- Disorganizzazione della struttura della membrana, alterazione della permeabilità, fuoriuscita dei componenti del citoplasma e lisi (distruzione) della cellula.
- Disposizione del peptide perpendicolarmente nella membrana, formazione di canali o “pori” e, anche in questo caso, morte della cellula.
- Alcuni peptidi, come la buforina, si sottraggono a questo meccanismo generale ed interagiscono direttamente con bersagli intracellulari (DNA e/o RNA) inibendo funzioni vitali per la cellula.
- Altri AMPs, agiscono con un meccanismo indipendente dal uccisione diretta dei microbi; sono in grado, infatti, di inibire la risposta proinfiammatoria dell’ospite e/o stimolare le reazioni immunitarie di difesa.
Le caratteristiche biologiche di queste molecole giustificano l’interesse suscitato nella comunità scientifica quali agenti terapeutici innovativi e alternativi, soprattutto nelle infezioni sostenute da microrganismi resistenti agli antibiotici. Diverse caratteristiche dei peptidi antimicrobici li rendono particolarmente interessanti come potenziali strumenti terapeutici:
- ampio spettro di attività: sono attivi contro virus, batteri, funghi e protozoi;
- rapida attività battericida (uccisione del 99,9% dei batteri a seguito di esposizione per 20 minuti);
- sono in grado di interagire in sinergia con gli antibiotici convenzionali;
- sono efficaci nei confronti di batteri che hanno sviluppato antibiotico-resistenza, in quanto possiedono meccanismi d’azione differenti rispetto ad alcuni antimicrobici.
In vitro è stata riscontrata l’efficacia dei peptidi antimicrobici del cane nei confronti di diversi batteri in grado di causare infezioni della pelle nel cane. I principali peptidi antimicrobici del cane (beta-defensine e catelicidina) si sono dimostrati attivi nei confronti di stafilococchi (Staphylococcus aureus e Staphylococcus pseudintermedius), Pseudomonas aeruginosa, Escherichia coli e di alcuni lieviti. In particolare è stato osservato che i peptidi antimicrobici del cane sembrano essere più efficaci nei confronti dei batteri e dei lieviti più comuni nel cane rispetto all’uomo. L’applicazione clinica di questi risultati sperimentali in ambito terapeutico potrebbe essere molto importante, dato che l’azione di questi peptidi non creerebbe problemi di resistenza agli antibiotici, sempre più comuni anche nel cane.
Attualmente, possono essere individuate diverse strategie nelle applicazioni terapeutiche dei peptidi: come singoli agenti anti-infettivi, in combinazione con antibiotici convenzionali per promuovere effetti additivi o sinergistici, come agenti immunomodulatori in grado di aumentare l’immunità innata naturale.
Nel complesso, i peptidi antimicrobici rappresentano una promettente alternativa terapeutica che sta ricevendo sempre maggiore attenzione dal mondo della ricerca.
Fonti:
Research gate.it
Dott. Raffaella Ripa tesi uni.
Icfresearch
Virbac research
D.C.
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