Thymol Disrupts Cell Homeostasis and Inhibits the Growth of Staphylococcus aureus

Abstract

Staphylococcus aureus (S. aureus) is a typical kind of symbiotic bacteria, which can cause human pneumonia, food poisoning, and other health problems. Nowadays, the corresponding prevention and treatment have been a hot issue of general concern in related research areas. However, the mechanism of action against S. aureus is not well understood. In order to tackle such problem, we used broth microdilution to discuss the antibacterial effect of 5-methyl-2-isopropylphenol and determine inhibitory concentration. In addition, membrane potential and lipid peroxidation levels were also measured under experimental conditions. The experimental results suggested that 300 μg/mL thymol might cause cell membrane damage and decrease of NADPH concentration and increase of NADP+ and lipid peroxidation level. In such condition, thymol has the potential to result in membrane rupture and disruption of cellular homeostasis. Furthermore, we also found that NOX2 is involved in maintaining the balance of NADPH/NADP+ in cells. Finally, our work confirms that NOX2 is a potential downstream target for thymol in the cell. Such target can provide specific guidance and recommendations for its application in antifungal activity. Meanwhile, our study also provides a new inspiration for the molecular mechanism of thymol’s bacteriostatic action.

Synergistic Activity of Thymol with Commercial Antibiotics against Critical and High WHO Priority Pathogenic Bacteria

“…According to literature reports, the most likely mechanism of action of THY is its ability to alter cell membranes [59,60]. On the one hand, the hydrophilic part of the molecule interacts with the polar part of the bacterial cell membrane while the hydrophobic benzene ring and lipid side chains of THY interact with the hydrophobic part of phospholipids, causing a loss of membrane stability and alterations in its permeability [22,61,62]. Although this seems to be the main mechanism, other studies specify that it may also have internal targets and interact at the mitochondrial level, causing the disruption of adenosine triphosphate (ATP) synthesis and inducing the generation of Na + and Ca 2+ metabolic disturbances, leading to an excess of oxygen free radicals that cause cell death [63,64].…”

“…Although this seems to be the main mechanism, other studies specify that it may also have internal targets and interact at the mitochondrial level, causing the disruption of adenosine triphosphate (ATP) synthesis and inducing the generation of Na + and Ca 2+ metabolic disturbances, leading to an excess of oxygen free radicals that cause cell death [63,64]. In S. aureus specifically, it has been described that THY is not only capable of disrupting the membrane and altering cellular homeostasis, but also affects the NADPH/NADP(+) balance in cells [61,65]. THY appears to be especially effective against Gram-positive bacteria, such as S. aureus and S. agalactiae.…”

PEI‐PLGA nanoparticles significantly enhanced the immunogenicity of IsdB137‐361 proteins from Staphylococcus aureus

“…Staphylococcus aureus causes multifarious infections in human and animal health, including in human‐related pneumonia, endocarditis, and mastitis in sheep and bovine 1–4 . Over the years, because clinical research have manifested that the vaccine is the most effective strategy in treating S. aureus infection, it is very necessary to develop an effective vaccine against S. aureus , 5–8 however, there is currently a lack of effective vaccine against S. aureus in the market.…”

“…Staphylococcus aureus causes multifarious infections in human and animal health, including in human‐related pneumonia, endocarditis, and mastitis in sheep and bovine. 1 , 2 , 3 , 4 Over the years, because clinical research have manifested that the vaccine is the most effective strategy in treating S. aureus infection, it is very necessary to develop an effective vaccine against S. aureus , 5 , 6 , 7 , 8 however, there is currently a lack of effective vaccine against S. aureus in the market. Our previous research showed that IsdB 137‐361 of the iron surface determinant B protein (IsdB) from S. aureus triggers a strong immune response in animal, but its immunoprotective effect is still to be further promoted.…”

Inhibitory Activity and Mechanism of Action with Thymol against the Blueberry Pathogenic Fungi Caused by Neopestalotiopsis clavispora

“…Its inhibitory effect is mainly attributed to the inhibition of ergosterol biosynthesis by disrupting the cell membrane and cell wall structural integrity of pathogenic fungus, and the inhibitory effect was mainly attributed to the inhibition of membrane lipid peroxidation caused by disrupting pathogenic cell membranes and, cell wall structural integrity [18], inhibiting ergosterol biosynthesis, and promoting cellular reactive oxygen species (ROS) radical accumulation. In addition, Li et al [19] discovered that NOX 2 was involved in maintaining the intracellular reduced nicotinamide adenine dinucleotide phosphate/oxidized nicotinamide adenine dinucleotide phosphate (NADPH/NADP+) balance in Staphylococcus aureus and caused a decrease in intracellular NADPH and ATP and an increase in NADP+ through thymol treatment, thus interfering with mycelial energy metabolism to exert antifungal activity.…”