Ellagic Acid Derivatives from Rubus ulmifolius Inhibit Staphylococcus aureus Biofilm Formation and Improve Response to Antibiotics

Abstract

BackgroundBiofilms contribute to the pathogenesis of many forms of Staphylococcus aureus infection. Treatment of these infections is complicated by intrinsic resistance to conventional antibiotics, thus creating an urgent need for strategies that can be used for the prevention and treatment of biofilm-associated infections.Methodology/Principal FindingsThis study demonstrates that a botanical natural product composition (220D-F2) rich in ellagic acid and its derivatives can limit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility. The source of this composition is Rubus ulmifolius Schott. (Rosaceae), a plant used in complementary and alternative medicine in southern Italy for the treatment of skin and soft tissue infections. All S. aureus clonal lineages tested exhibited a reduced capacity to form a biofilm at 220D-F2 concentrations ranging from 50–200 µg/mL, which were well below the concentrations required to limit bacterial growth (530–1040 µg/mL). This limitation was therapeutically relevant in that inclusion of 220D-F2 resulted in enhanced susceptibility to the functionally-distinct antibiotics daptomycin, clindamycin and oxacillin. Testing with kidney and liver cell lines also demonstrated a lack of host cell cytotoxicity at concentrations of 220D-F2 required to achieve these effects.Conclusions/SignificanceThese results demonstrate that extract 220D-F2 from the root of Rubus ulmifolius can be used to inhibit S. aureus biofilm formation to a degree that can be correlated with increased antibiotic susceptibility without toxic effects on normal mammalian cells. Hence, 220D-F2 is a strong candidate for development as a botanical drug for use in the prevention and treatment of S. aureus biofilm-associated infections.

Novel Antibiotic-loaded Point-of-care Implant Coating Inhibits Biofilm

“…The reduction in biofilm attachment in a challenging polymicrobial in vivo model confirms the in vitro results and is consistent with release of active concentrations of antibiotic from various drug delivery vehicles [22,45,51,54,63]. Scanning electron microscopy images of biofilm formation on implants resembled images from similar retrieved infected implants [10,52] with rounded S aureus and rod-shaped P aeruginosa colonies visible in untreated groups.…”

“…The limitations of the animal model include the small size, soft tissue instead of orthopaedic implantation, and limited diffusion of physiologic substances within the sequestrum of the catheter. The animal model is useful as a screening tool for antibiofilm activity in vivo [54,74,75], where the catheter serves as a sequestrum for localizing the bacterial inoculum and as a nidus for biofilm formation. Because of difficulty in applying coatings directly to the catheter, we modified the catheter-associated biofilm model by including an easily coated stainless steel wire.…”

Tannic Acid Inhibits Staphylococcus aureus Surface Colonization in an IsaA-Dependent Manner

“…Pentagalloyl glucose (one of the major components of commercial tannic acid) and ellagic acid (another plant-derived polyphenolic compound) have also been shown to inhibit biofilm formation in S. aureus (46,47). To the best of our knowledge, no genetic mechanism for the antibiofilm properties of tannic acid or related polyphenols in S. aureus has been proposed.…”

CHAPTER 14. Antimicrobial Interfaces

“…11 It was reported that bacteria within a biofilm can reach a much higher cell density (10 11 CFU mL À1 ) than do planktonic bacteria (10 8 CFU mL À1 ). 27 A number of the quorum-sensing signals involved in biofilm formation have already been identified but many of them remain unidentified. In addition, biofilm development needs the activation and suppression of a wide array of genes.…”