Synergistic Antibacterial Effect and Antibacterial Action Mode of Chitosan-Ferulic Acid Conjugate against Methicillin-Resistant Staphylococcus aureus

Abstract

The object of this study was to discover an alternative therapeutic agent with fewer side effects against acne vulgaris, which is one of the most common skin diseases. Acne vulgaris often associates with acne-related bacteria such as Propionibacterium acnes, Staphylococcus epidermidis, Staphylococcus aureus and Pseudomonas aeruginosa, some of which exhibit a resistant against commercial antibiotics used in the treatment of acne vulgaris (tetracycline, erythromycin, and lincomycin). In the current study, we evaluated in vitro antibacterial activity of chitosan-phytochemical conjugates against acne-related bacteria. Three of chitosan-phytochemical conjugates used in this study showed stronger antibacterial activity than that of chitosan (unmodified control). Chitosan-caffeic acid conjugate (CCA) exhibited the highest antibacterial activity against acne-related bacteria with minimum inhibitory concentration values of 8 μg/mL to 256 μg/mL. In addition, the MICs of antibiotics against antibiotic resistant P. acnes and P. aeruginosa strains were dramatically reduced in the combination with CCA, suggesting that CCA would restore the antibacterial activity of the antibiotics. The analysis of fractional inhibitory concentration indices clearly revealed a synergistic antibacterial effect between CCA and the antibiotics. Thus, the median ∑FIC values against the antibiotic resistant bacterial strains were ranged from 0.375 to 0.533 in the combination mode of CCA and antibiotics.

Synergistic Antibacterial Effects of Chitosan-Caffeic Acid Conjugate against Antibiotic Resistant Acne-Related Bacteria

“…These results were also accordance with the report by Eom et al [12] that chitosan-derived conjugates clearly reversed antibacterial activity of β-lactam antibiotics against methicillin-resistant S. aureus (MRSA) in the combination mode. The median ΣFIC indices were in the ranges of 0.375 to 0.563.…”

“…It has been demonstrated that one of the more effective strategies in developing new drugs or alternative therapies is the restoration of antibiotic activity in combination with antibacterial materials derived from natural products and traditional medicines against drugresistant bacteria [12,[30][31][32]. Based on these reports, an interaction between chitosan-phytochemicals and commercial antibiotics were estimated by the checkerboard method as stated above and the results were presented in Table 3.…”

“…In this study, chitosan-phytochemical conjugates were synthesized by conjugating HAs into the chitosan backbone according to the previous method [12,18]. It was then assessed an antibacterial activity of chitosan-phytochemical conjugates against acne-related bacteria.…”

“…Chitosan is one of mucopolysaccharides of marine origin, being biodegradable, biocompatible, and low-toxicity. It has been applied to food and pharmaceutical industry due to its several bioactivities including antiinflammatory, antioxidant, antitumor, and enzymatic inhibitory effect [11][12][13]. Therefore, there is a growing interest in developing novel chitosan derivatives with a novel functionality [14].…”

“…However, as described above, most studies related chitosan and its derivatives have been focused on the biological activities such as antioxidant, antitumor, and anti-inflammatory effect, not antimicrobial activity [15][16][17]. It has been previously reported that chitosan derivatives conjugated with phytochemicals (caffeic acid, ferulic acid, and sinapic acid), which exhibited strong antibacterial activity against pathogenic bacteria [12,18]. However, no further experiment was progressed against other pathogenic bacteria, especially acne-related bacteria.…”