Meticillin-resistant Staphylococcus aureus infection in diabetic mice enhanced inflammation and coagulation.

BALB/cA mice were used to study the interaction of diabetes and meticillin-resistant Staphylococcus aureus (MRSA) infection on pathogen distribution, cytokine profile and inflammatory and endothelial-injury markers, as well as coagulation and anticoagulation factors. Meticillin-susceptible S. aureus (MSSA) infection did not cause death within the experimental period. MRSA-infected nondiabetic and diabetic mice died on 19.1+/-1.4 and 10.6+/-0.7 days post-infection (p.i.), respectively. MRSA and MSSA infection in diabetic mice did not result in symptomatic bacteraemia; however, MRSA infection in diabetic mice significantly reduced glucose levels (P<0.05). Diabetic mice showed significantly higher levels of C-reactive protein, fibrinogen, fibronectin and von Willebrand factor than nondiabetic mice (P<0.05), and MRSA infection further elevated the plasma levels of these inflammatory and endothelial markers (P<0.05). Before infection, diabetic mice had significantly higher plasminogen activator inhibitor-1 (PAI-1) activity, lower antithrombin III (AT-III) and protein C activities (P<0.05), and MRSA infection significantly increased PAI-1 activity further and reduced the activity of AT-III and protein C (P<0.05). MRSA infection increased the production of three Th1 cytokines, interleukin 2 (IL-2), tumour necrosis factor alpha and gamma interferon, in diabetic mice (P<0.05); however, three Th2 cytokines, IL-4, IL-6, IL-10, were elevated at 2 and 4 days p.i., and then dropped gradually. MRSA infection in diabetic mice accelerated the inflammation process, endothelial injury and blood coagulation in diabetic mice. Therefore, the development of proper infection diagnosis and timely use of effective treatments for MRSA-infected diabetic individuals is important and necessary.

In vitro antibacterial activity of roselle calyx and protocatechuic acid.

The in vitro inhibitory effect of roselle calyx and protocatechuic acid, a compound derived from roselle calyx, on the growth of methicillin-resistant Staphylococcus aureus, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii was studied. The data from inhibition zone and minimum inhibitory concentration (MIC) values showed that both roselle calyx extract and protocatechuic acid inhibited effectively the growth of all test bacterial pathogens, the antibacterial activity of protocatechuic acid being significantly greater than roselle calyx (p < 0.05). Furthermore, heat treatment did not affect the antibacterial activity of roselle calyx and protocatechuic acid against all test pathogens. The time-kill data from protocatechuic acid showed this agent provided concentration dependent antibacterial activities in broth and human plasma (p < 0.05); however, protocatechuic acid showed less inhibitory activity in human plasma than in broth (p < 0.05). These agents based on their lower MIC values, heat tolerance and concentration dependent antibacterial activity may be useful in clinical infection prevention or therapy.

Garlic extract and two diallyl sulphides inhibit methicillin-resistant Staphylococcus aureus infection in BALB/cA mice.

OBJECTIVES: The inhibitory effect of garlic extract, diallyl sulphide and diallyl disulphide against methicillin-resistant Staphylococcus aureus (MRSA) infection in BALB/cA mice was studied. The influence of these agents upon the levels of fibronectin, interleukin-6 and lipid oxidation in MRSA-infected mice was examined. METHODS: Garlic extract at 100% and 50%; diallyl sulphide (DAS) at 10% and 5%; diallyl disulphide (DADS) at 1% and 0.5% were used in this study. Sixteen clinical MRSA isolates obtained from infected patients were used in this study (n=16). Mice were infected by injecting 200 microL MRSA-PBS solution, which contained 10(7) cfu, via the tail vein. At 16 h post-infection (p.i.), garlic extract, DAS or DADS at 200 microL was administrated orally. At 24 h p.i., mice were killed and blood, liver, kidney and spleen of each mouse were collected. Plasma and the filtrate from each organ and serial dilutions were used to determine colony count. Plasma fibronectin level was determined by rabbit anti-rat fibronectin antibody and quantified by ELISA. Interleukin-6 levels were determined by commercial kit. Lipid oxidation was determined by measuring malondialdehyde levels. RESULTS: The oral administration of these agents significantly decreased the viability of MRSA, in plasma, liver, kidney and spleen (P<0.05). MRSA infection significantly increased fibronectin and interleukin-6 levels in plasma of MRSA-infected mice (P<0.05); however, the oral administration of garlic extract and two diallyl sulphides significantly reduced both fibronectin and interleukin-6 levels (P<0.05). MRSA infection also significantly enhanced lipid oxidation in plasma and three organs (P<0.05). The treatments of garlic extract and two diallyl sulphides significantly decreased the malondialdehyde level and showed antioxidant protection (P<0.05). CONCLUSIONS: These data strongly supported the conclusion that garlic extract, diallyl sulphide and diallyl disulphide possessed multiple protective functions against MRSA infection, in which diallyl sulphide and diallyl disulphide could be considered as novel therapeutic agents for the treatment of MRSA infection.

Protective action on human LDL against oxidation and glycation by four organosulfur compounds derived from garlic.

Human LDL were used to study the protective action of four organosulfur compounds (diallyl sulfide, DAS; diallyl disulfide, DADS; S-ethylcysteine, SEC; N-acetylcysteine, NAC) derived from garlic against oxidation and glycation. The four organosulfur compounds significantly inhibited superoxide production by xanthine-xanthine oxidase (P < 0.05) and showed marked copper-chelating capability. DAS and DADS exhibited greater antioxidant activities against copper- and amphotericin B-induced LDL oxidation (P < 0.05) than SEC and NAC. However, SEC and NAC were more effective in sparing LDL alpha-tocopherol (P < 0.05). When oxidation was minimized, SEC was the most powerful agent against LDL glycation (P < 0.05); however, DADS was superior to other agents in suppressing both oxidation and glycation when LDL oxidation occurred simultaneously with glycation. These results suggest that the four organosulfur compounds derived from garlic are potent agents for protecting LDL against oxidation and glycation, and that they may benefit patients with diabetes mellitus or cardiovascular diseases by preventing complications.

In-vitro antimicrobial activity of four diallyl sulphides occurring naturally in garlic and Chinese leek oils.

The in-vitro antimicrobial activity of garlic oil, Chinese leek oil and four diallyl sulphides occurring naturally in these oils against Staphylococcus aureus, methicillin-resistant S. aureus (MRSA), three Candida spp. and three Aspergillus spp. (total of 276 clinical isolates) was studied. The magnitude of activity of the four diallyl sulphides followed the order diallyl tetrasulphide > diallyl trisulphide > diallyl disulphide > diallyl monosulphide. These results suggest that disulphide bonds are an important factor in determining the antimicrobial capabilities of these sulphides. The concentration of four diallyl sulphides in garlic and Chinese leek oils was in the range 41.7-52.7% of total sulphides. Garlic oil, with a higher concentration of four diallyl sulphides, showed greater antimicrobial activity than Chinese leek oil. Diallyl disulphide, diallyl trisulphide, diallyl tetrasulphide and the oils rich in these sulphides may have a role in the prevention or treatment of infections.