9 Citazioni (Scopus)

Abstract

There are few therapeutic options to simultaneously tackle Staphylococcus aureus and Pseudomonas aeruginosa, two of the most relevant nosocomial and antibiotic-resistant pathogens responsible for implant, catheters and wound severe infections. The design and synthesis of polymers with inherent antimicrobial activity have gained increasing attention as a safe strategy to treat multi-drug-resistant microbes. Here, we tested the activity of a new polymeric derivative with glycopolypeptide architecture (PAA-VC) bearing l-arginine, vancomycin, and colistin as side chains acting against multiple targets, which give rise to a broad spectrum antimicrobial activity favorably combining specific and nonspecific perturbation of the bacterial membrane. PAA-VC has been tested against planktonic and established biofilms of reference strains S. aureus ATCC 25923 and P. aeruginosa ATCC 15442 and susceptible or antibiotic resistant clinical isolates of the above-mentioned microorganisms. MIC values observed for the conjugate (48-190 and 95-190 nM for P. aeruginosa and S. aureus strains, respectively) showed higher efficacy if compared with the free vancomycin (MICs within 1.07-4.28 μM) and colistin (MICs within 0.63-1.33 μM). Additionally, being highly biocompatible (IC50 > 1000, 430, and 250 μg mL-1 for PAA-VC, vancomycin and colistin respectively) high-dosage can be adopted for the eradication of infections in patients. This positively influences the anti-biofilm activity of the conjugate leading to a quasi-total eradication of established clinically relevant biofilms (inhibition >90% at 500 μg mL-1). We believe that the in vitro presented data, especially the activity against established biofilms of two relevant pathogens, the high biocompatibility and the good mucoadhesion properties, would allow the use of PAA-VC as promising candidate to successfully address emerging infections.
Lingua originaleEnglish
pagine (da-a)318-331
Numero di pagine14
RivistaACS APPLIED MATERIALS & INTERFACES
Volume10
Stato di pubblicazionePublished - 2018

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Biofilms
Colistin
Vancomycin
Molecular weight
Pathogens
Antibiotics
Bearings (structural)
Anti-Bacterial Agents
Arginine
Catheters
Biocompatibility
Microorganisms
Polymers
Derivatives
Membranes
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Materials Science(all)

Cita questo

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title = "Branched High Molecular Weight Glycopolypeptide With Broad-Spectrum Antimicrobial Activity for the Treatment of Biofilm Related Infections",
abstract = "There are few therapeutic options to simultaneously tackle Staphylococcus aureus and Pseudomonas aeruginosa, two of the most relevant nosocomial and antibiotic-resistant pathogens responsible for implant, catheters and wound severe infections. The design and synthesis of polymers with inherent antimicrobial activity have gained increasing attention as a safe strategy to treat multi-drug-resistant microbes. Here, we tested the activity of a new polymeric derivative with glycopolypeptide architecture (PAA-VC) bearing l-arginine, vancomycin, and colistin as side chains acting against multiple targets, which give rise to a broad spectrum antimicrobial activity favorably combining specific and nonspecific perturbation of the bacterial membrane. PAA-VC has been tested against planktonic and established biofilms of reference strains S. aureus ATCC 25923 and P. aeruginosa ATCC 15442 and susceptible or antibiotic resistant clinical isolates of the above-mentioned microorganisms. MIC values observed for the conjugate (48-190 and 95-190 nM for P. aeruginosa and S. aureus strains, respectively) showed higher efficacy if compared with the free vancomycin (MICs within 1.07-4.28 μM) and colistin (MICs within 0.63-1.33 μM). Additionally, being highly biocompatible (IC50 > 1000, 430, and 250 μg mL-1 for PAA-VC, vancomycin and colistin respectively) high-dosage can be adopted for the eradication of infections in patients. This positively influences the anti-biofilm activity of the conjugate leading to a quasi-total eradication of established clinically relevant biofilms (inhibition >90{\%} at 500 μg mL-1). We believe that the in vitro presented data, especially the activity against established biofilms of two relevant pathogens, the high biocompatibility and the good mucoadhesion properties, would allow the use of PAA-VC as promising candidate to successfully address emerging infections.",
author = "Domenico Schillaci and Nicol{\`o} Mauro and Geraci, {Daniela Maria} and Cusimano, {Maria Grazia} and Mario Giuffre and Gennara Cavallaro and Maida, {Carmelo Massimo} and Gaetano Giammona and Paola Varvara' and Gaetano Giammona",
year = "2018",
language = "English",
volume = "10",
pages = "318--331",
journal = "ACS APPLIED MATERIALS & INTERFACES",
issn = "1944-8244",

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TY - JOUR

T1 - Branched High Molecular Weight Glycopolypeptide With Broad-Spectrum Antimicrobial Activity for the Treatment of Biofilm Related Infections

AU - Schillaci, Domenico

AU - Mauro, Nicolò

AU - Geraci, Daniela Maria

AU - Cusimano, Maria Grazia

AU - Giuffre, Mario

AU - Cavallaro, Gennara

AU - Maida, Carmelo Massimo

AU - Giammona, Gaetano

AU - Varvara', Paola

AU - Giammona, Gaetano

PY - 2018

Y1 - 2018

N2 - There are few therapeutic options to simultaneously tackle Staphylococcus aureus and Pseudomonas aeruginosa, two of the most relevant nosocomial and antibiotic-resistant pathogens responsible for implant, catheters and wound severe infections. The design and synthesis of polymers with inherent antimicrobial activity have gained increasing attention as a safe strategy to treat multi-drug-resistant microbes. Here, we tested the activity of a new polymeric derivative with glycopolypeptide architecture (PAA-VC) bearing l-arginine, vancomycin, and colistin as side chains acting against multiple targets, which give rise to a broad spectrum antimicrobial activity favorably combining specific and nonspecific perturbation of the bacterial membrane. PAA-VC has been tested against planktonic and established biofilms of reference strains S. aureus ATCC 25923 and P. aeruginosa ATCC 15442 and susceptible or antibiotic resistant clinical isolates of the above-mentioned microorganisms. MIC values observed for the conjugate (48-190 and 95-190 nM for P. aeruginosa and S. aureus strains, respectively) showed higher efficacy if compared with the free vancomycin (MICs within 1.07-4.28 μM) and colistin (MICs within 0.63-1.33 μM). Additionally, being highly biocompatible (IC50 > 1000, 430, and 250 μg mL-1 for PAA-VC, vancomycin and colistin respectively) high-dosage can be adopted for the eradication of infections in patients. This positively influences the anti-biofilm activity of the conjugate leading to a quasi-total eradication of established clinically relevant biofilms (inhibition >90% at 500 μg mL-1). We believe that the in vitro presented data, especially the activity against established biofilms of two relevant pathogens, the high biocompatibility and the good mucoadhesion properties, would allow the use of PAA-VC as promising candidate to successfully address emerging infections.

AB - There are few therapeutic options to simultaneously tackle Staphylococcus aureus and Pseudomonas aeruginosa, two of the most relevant nosocomial and antibiotic-resistant pathogens responsible for implant, catheters and wound severe infections. The design and synthesis of polymers with inherent antimicrobial activity have gained increasing attention as a safe strategy to treat multi-drug-resistant microbes. Here, we tested the activity of a new polymeric derivative with glycopolypeptide architecture (PAA-VC) bearing l-arginine, vancomycin, and colistin as side chains acting against multiple targets, which give rise to a broad spectrum antimicrobial activity favorably combining specific and nonspecific perturbation of the bacterial membrane. PAA-VC has been tested against planktonic and established biofilms of reference strains S. aureus ATCC 25923 and P. aeruginosa ATCC 15442 and susceptible or antibiotic resistant clinical isolates of the above-mentioned microorganisms. MIC values observed for the conjugate (48-190 and 95-190 nM for P. aeruginosa and S. aureus strains, respectively) showed higher efficacy if compared with the free vancomycin (MICs within 1.07-4.28 μM) and colistin (MICs within 0.63-1.33 μM). Additionally, being highly biocompatible (IC50 > 1000, 430, and 250 μg mL-1 for PAA-VC, vancomycin and colistin respectively) high-dosage can be adopted for the eradication of infections in patients. This positively influences the anti-biofilm activity of the conjugate leading to a quasi-total eradication of established clinically relevant biofilms (inhibition >90% at 500 μg mL-1). We believe that the in vitro presented data, especially the activity against established biofilms of two relevant pathogens, the high biocompatibility and the good mucoadhesion properties, would allow the use of PAA-VC as promising candidate to successfully address emerging infections.

UR - http://hdl.handle.net/10447/256630

M3 - Article

VL - 10

SP - 318

EP - 331

JO - ACS APPLIED MATERIALS & INTERFACES

JF - ACS APPLIED MATERIALS & INTERFACES

SN - 1944-8244

ER -