Antibacterial and synergic effects of gallic acid-grafted-chitosan with β-lactams against methicillin-resistant Staphylococcus aureus (MRSA)

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is spreading worldwide, emphasizing the need to search for new antibiotics. The anti-MRSA activities of gallic acid-grafted-chitosans (GA-g-chitosans) were investigated against 2 MRSA standards and 10 MRSA clinical isolates by determining the minimum inhibitory concentrations (MICs). GA-g-chitosan (I), which has the highest gallic acid content, exhibited the strongest anti-MRSA activities, with MICs of 32-64 μg/mL. A time-kill investigation revealed that GA-g-chitosan (I) exhibited a bactericidal effect at twice the MIC, also demonstrating good thermal and pH stability. Investigation of cell envelope integrity showed the release of intracellular components with an increasing absorbance value at 260 nm, indicating cell envelope damage caused by the GA-g-chitosan (I), which was further confirmed by transmission electron microscopy. When GA-g-chitosans were combined with β-lactams, including ampicillin and penicillin, synergistic effects were observed on the 2 standard MRSA strains and on the 10 clinical isolates, with fractional inhibitory indices ranging from 0.125 to 0.625. In the time-kill dynamic confirmation test, synergistic bactericidal effects were observed for the combinations of GA-g-chitosans with β-lactams, and over 4.0 log CFU/mL reductions were observed after 24 h when combination treatment was used. These results may prove GA-g-chitosans to be a potent agent when combined with ampicillin and penicillin for the elimination of MRSA.

Gallic Acid-g-Chitosan Modulates Inflammatory Responses in LPS-Stimulated RAW264.7 Cells Via NF-κB, AP-1, and MAPK Pathways

“…Herein, we firstly reported the anti-inflammatory action of GAC and proved the underlying mechanism. Previously, we proved many biological activities of GAC such as antibacterial [7,8] and antioxidant [5,6], and GAC showed better biological activities compared to those of unmodified chitosan. Moreover, high molecular weight chitosan is insoluble in water; thus, it is hard to measure such biological activities in the water system.…”

“…However, chitosan is supposed to modify its chemical properties by enzymatic hydrolysis and/or chemical modification for industrial applications due to the low solubility in water as well as enhancement of biological activities. In a previous work, grafting gallic acid onto chitosan via the free radical-mediated conjugation method has been shown to enhance biological activities including antioxidant and antimicrobial activities [5][6][7][8].…”

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

“…Positively charged chitosan interacts with the negatively charged bacterial cell surface, leading to weakening of the cell wall either by cell wall damage alone or accompanied by cell lysis [25,34]. Furthermore, chitosan conjugated with HAs increase the affinity of chitosan for bacterial cell envelope composed with lipid layer because of lipophilicity of HAs possessing unsaturated chain [18,35].…”

“…Furthermore, chitosan conjugated with HAs increase the affinity of chitosan for bacterial cell envelope composed with lipid layer because of lipophilicity of HAs possessing unsaturated chain [18,35]. In analogy to chitosan-polyphenol conjugates, the antibacterial activity of chitosan phytochemical conjugates were accelerated by affecting bacterial cell envelope integrity and altering cell permeability by means of interacting with the envelope [25,36]. Up to date, there are several reports on the control of acne-related bacteria.…”

“…Also, it has been previously reported on the antibiotic resistance of acne-related bacteria. According to the report by Lee et al [25], P. acnes strains have high-level resistance to erythromycin (MIC of 2,048 μg/mL). However, S. epidermidis and S. aureus were found to be sensitive for tetracycline, erythromycin, and lincomycin in the MIC ranges of 0.125 μg/mL to 8 μg/mL.…”