Abstract
Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to a number of antibiotics of clinical importance and is a serious threat to public health. Since bacteria rapidly develop resistance even to newly discovered antibiotics, this study aimed to develop drug potentiators to enhance the antibacterial activity of existing antibiotics for the control of MRSA. Based on our previous studies, screening of antimicrobial synergy was conducted with gallic acid and its derivatives using checkerboard assays. Antimicrobial synergy was confirmed with MRSA isolates from clinical cases. Combinations of penicillin, ampicillin, and cephalothin with octyl gallate (OG), an antioxidant approved by the US Food and Drug Administration (FDA), consistently exhibited synergistic bacteriostatic and bactericidal activities against MRSA, rendering MRSA sensitive to β-lactams. The fractional inhibitory concentration (FIC) and fractional bactericidal concentration (FBC) indices exhibited that the antimicrobial effects of OG were synergistic. The results of a permeability assay showed that OG significantly increased the permeability of the bacterial cell wall. Despite the intrinsic resistance of MRSA to β-lactams, the findings in this study demonstrated that OG enhanced the activity of β-lactams in MRSA and sensitized MRSA to β-lactams, suggesting that OG can be used as a drug potentiator to control MRSA using existing antibiotics.
Highlights
Multidrug-resistant bacterial infections are a rapidly growing threat to public health worldwide [1,2]
We demonstrated that the antimicrobial and anti-biofilm activities of bacitracin, an antimicrobial peptide, were synergistically increased in methicillin-resistant Staphylococcus aureus (MRSA) when combined with octyl gallate (OG), a food additive approved by the U.S Food and Drug Administration (FDA) to prevent lipid oxidation [13,14]
Since our previous studies showed that some gallic acid derivates generated antimicrobial synergy with bacitracin [13,14], in this study, we investigated whether gallic acid derivatives may increase antimicrobial activity in MRSA when used in combination with antibiotics of other classes
Summary
Multidrug-resistant bacterial infections are a rapidly growing threat to public health worldwide [1,2]. Methicillin-resistant Staphylococcus aureus (MRSA) is resistant to many conventional antibiotic therapies and frequently implicated in fatal infections, such as bacteremia, endocarditis, and pneumonia, and poses a significant threat to public health [3]. MRSA is resistant to all β-lactams and other clinically important antibiotics, such as linezolid and daptomycin, and increasingly resistant to the last-resort antibiotics, such as vancomycin [4,5,6,7], further limiting therapeutic options to treat MRSA infections. Several new antimicrobial agents have been introduced to control MRSA infections, MRSA remains difficult to treat [9]. New antibiotics are urgently needed for the treatment of antibiotic-resistant infections
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