Cinnamaldehyde Restores Ceftriaxone Susceptibility against Multidrug-Resistant Salmonella.

In recent years, infections caused by multidrug-resistant (MDR) bacteria have greatly threatened human health and imposed a burden on global public health. To overcome this crisis, there is an urgent need to seek effective alternatives to single antibiotic therapy to circumvent drug resistance and prevent MDR bacteria. According to previous reports, cinnamaldehyde exerts antibacterial activity against drug-resistant Salmonella spp. This study was conducted to investigate whether cinnamaldehyde has a synergistic effect on antibiotics when used in combination, we found that cinnamaldehyde enhanced the antibacterial activity of ceftriaxone sodium against MDR Salmonella in vitro by significantly reduced the expression of extended-spectrum beta-lactamase, inhibiting the development of drug resistance under ceftriaxone selective pressure in vitro, damaging the cell membrane, and affecting its basic metabolism. In addition, it restored the activity of ceftriaxone sodium against MDR Salmonella in vivo and inhibited peritonitis caused by ceftriaxone resistant strain of Salmonella in mice. Collectively, these results revealed that cinnamaldehyde can be used as a novel ceftriaxone adjuvant to prevent and treat infections caused by MDR Salmonella, mitigating the possibility of producing further mutant strains.

Geraniol inhibits biofilm formation of methicillin-resistant Staphylococcus aureus and increase the therapeutic effect of vancomycin in vivo.

Methicillin-resistant Staphylococcus aureus (MRSA) is among the common drug resistant bacteria, which has gained worldwide attention due to its high drug resistance and infection rates. Biofilms produced by S. aureus are known to increase antibiotic resistance, making the treatment of S. aureus infections even more challenging. Hence, inhibition of biofilm formation has become an alternative strategy for controlling persistent infections. In this study, we evaluated the efficacy of geraniol as a treatment for MRSA biofilm infection. The results of crystal violet staining indicated that 256 µg/mL concentration of geraniol inhibited USA300 biofilm formation by 86.13% and removed mature biofilms by 49.87%. Geraniol exerted its anti-biofilm effect by influencing the major components of the MRSA biofilm structure. We found that geraniol inhibited the synthesis of major virulence factors, including staphyloxanthin and autolysins. The colony count revealed that geraniol inhibited staphyloxanthin and sensitized USA300 cells to hydrogen peroxide. Interestingly, geraniol not only reduced the release of extracellular nucleic acids (eDNA) but also inhibited cell autolysis. Real-time polymerase chain reaction data revealed the downregulation of genes involved in biofilm formation, which verified the results of the phenotypic analysis. Geraniol increased the effect of vancomycin in eliminating USA300 biofilms in a mouse infection model. Our findings revealed that geraniol effectively inhibits biofilm formation in vitro. Furthermore, in combination with vancomycin, geraniol can reduce the biofilm adhesion to the implant in mice. This suggests the potential of geraniol as an anti-MRSA biofilm drug and can provide a solution for the clinical treatment of biofilm infection.

The antibacterial mechanism of oridonin against methicillin-resistant Staphylococcus aureus (MRSA).

Context: Methicillin-resistant Staphylococcus aureus (MRSA) is a very harmful bacterium. Oridonin, a component in Rabdosia rubescens (Hemsl.) Hara (Lamiaceae), is widely used against bacterial infections in China. Objective: We evaluated oridonin effects on MRSA cell membrane and wall, protein metabolism, lactate dehydrogenase (LDH), DNA and microscopic structure. Materials and methods: Broth microdilution and flat colony counting methods were used to measure oridonin minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) against USA300 strain. Electrical conductivity and DNA exosmosis were analysed to study oridonin effects (128 µg/mL) on cell membrane and wall for 0, 1, 2, 4 and 6 h. Sodium dodecyl sulphate polyacrylamide gel electrophoresis was used to detect effects on soluble protein synthesis after 6, 10 and 16 h. LDH activity was examined with an enzyme-linked immunosorbent assay. Effects of oridonin on USA300 DNA were investigated with DAPI staining. Morphological changes in MRSA following oridonin treatment were determined with scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: Oridonin MIC and MBC values against USA300 were 64 and 512 µg/mL, respectively. The conductivity and DNA exosmosis level of oridonin-treated USA300 improved by 3.20±0.84% and increased by 58.63 ± 1.78 µg/mL, respectively. LDH and soluble protein levels decreased by 30.85±7.69% and 27.51 ± 1.39%, respectively. A decrease in fluorescence intensity was reported with time. Oridonin affected the morphology of USA300. Conclusions: Oridonin antibacterial mechanism was related to changes in cell membrane and cell wall permeability, disturbance in protein and DNA metabolism, and influence on bacterial morphology. Thus, oridonin may help in treating MRSA infection.