Synergistic activity of dispersin B and cefamandole nafate in inhibition of staphylococcal biofilm growth on polyurethanes.
Antibiotic therapies to eradicate medical device-associated infections often fail because of the ability of sessile bacteria, encased in their exopolysaccharide matrix, to be more drug resistant than planktonic organisms. In the last two decades, several strategies to prevent microbial adhesion and biofilm formation on the surfaces of medical devices, based mainly on the use of antiadhesive, antiseptic, and antibiotic coatings on polymer surfaces, have been developed. More recent alternative approaches are based on molecules able to interfere with quorum-sensing phenomena or to dissolve biofilms. Interestingly, a newly purified beta-N-acetylglucosaminidase, dispersin B, produced by the gram-negative periodontal pathogen Actinobacillus actinomycetemcomitans, is able to dissolve mature biofilms produced by Staphylococcus epidermidis as well as some other bacterial species. Therefore, in this study, we developed new polymeric matrices able to bind dispersin B either alone or in combination with an antibiotic molecule, cefamandole nafate (CEF). We showed that our functionalized polyurethanes could adsorb a significant amount of dispersin B, which was able to exert its hydrolytic activity against the exopolysaccharide matrix produced by staphylococcal strains. When microbial biofilms were exposed to both dispersin B and CEF, a synergistic action became evident, thus characterizing these polymer-dispersin B-antibiotic systems as promising, highly effective tools for preventing bacterial colonization of medical devices.
Donelli
G
G
Department of Technologies and Health, Istituto Superiore di Sanità, Viale Regina Elena, Rome, Italy. gianfranco.donelli@iss.it
Francolini
I
I
Romoli
D
D
Guaglianone
E
E
Piozzi
A
A
Ragunath
C
C
Kaplan
J B
JB
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D002435:Cefamandole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004347:Drug Interactions; D006026:Glycoside Hydrolases / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D011140:Polyurethanes / Q000737:chemistry; D016459:Prosthesis-Related Infections / Q000517:prevention & control; D013210:Staphylococcus / Q000187:drug effects* / Q000254:growth & development; D013211:Staphylococcus aureus / Q000187:drug effects / Q000254:growth & development; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000254:growth & development
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011140:Polyurethanes; D002435:Cefamandole; C012810:cefamandole nafate; D006026:Glycoside Hydrolases; C501330:dispersin B, Actinobacillus actinomycetemcomitans