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

Gu, Kexin; Ouyang, Ping; Hong, Yuxin; Dai, Yuyun; Tang, Ting; He, Chao; Shu, Gang; Liang, Xiaoxia; Tang, Huaqiao; Zhu, Ling; Xu, Zhiwen; Yin, Lizi

doi:10.3389/fmicb.2022.960728

Cited by 12 publications

(7 citation statements)

References 56 publications

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“…Aside from QS system, the SarA regulatory system is also involved in the regulation of biofilm formation ( 43 ). The role of SarA regarding biofilm formation is to repress the production of extracellular proteases and PIA, and induce the expression of fnbA , fnbB , and clfA (determinants of S. aureus surface adhesins) ( 44 ). In our study, we found that exposure to sub-inhibitory concentrations of S-342-3 resulted in a reduction in the expression of the regulatory gene sarA .…”

Section: Discussionmentioning

confidence: 99%

A novel small-molecule compound S-342-3 effectively inhibits the biofilm formation of Staphylococcus aureus

Zhang,

Shen,

Zhou

et al. 2023

Microbiol Spectr

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Staphylococcus aureus is an important human pathogen in both community and hospital settings that often causes persistent and recurrent infections. The continuous emergence of multidrug-resistant strains and the lag in antibiotic development make the treatment of S. aureus more challenging. The biofilm formation of S. aureus is an important reason for persistent infection. In this study, we demonstrated that a small-molecule compound S-342-3 can effectively inhibit the biofilm formation of S. aureus . The crystal violet semi-quantitative assays revealed that at a sub-minimum inhibitory concentration of 4 µg/mL, S-342-3 reduced S. aureus biofilm mass by 57.43%, 52.14%, and 25.49%. Using confocal laser scanning microscopy, we observed that the biofilm was more incompact and less uniform upon the treatment of S-342-3. At a sub-inhibitory concentration (4 µg/mL), the S-342-3 can effectively reduce the production of polysaccharide intercellular adhesin (PIA) and suppress the initial adhesion of cells in the biofilm. Consistently, the results of RT-qPCR revealed that the expression of genes associated with biofilm formation was downregulated by S-342-3 ( P < 0.05). However, we found that treatment with S-342-3 resulted in a significant decrease in the expression of global regulatory genes agrA and sarA ( P < 0.05), which play a key role in promoting cell surface attachment and PIA production in S. aureus biofilms. Also importantly, we experimentally proved that the S-342-3 was not toxic to A549 alveolar epithelial cells and the Galleria mellonella larvae. Collectively, these results suggest that the S-342-3 may be a promising anti-biofilm drug candidate with excellent biosafety, which can be further explored for its practical application in health care. IMPORTANCE Biofilms are an important virulence factor in Staphylococcus aureus and are characterized by a structured microbial community consisting of bacterial cells and a secreted extracellular polymeric matrix. Inhibition of biofilm formation is an effective measure to control S. aureus infection. Here, we have synthesized a small molecule compound S-342-3, which exhibits potent inhibition of biofilm formation in both MRSA and MSSA. Further investigations revealed that S-342-3 exerts inhibitory effects on biofilm formation by reducing the production of polysaccharide intercellular adhesin and preventing bacterial adhesion. Our study has confirmed that the inhibitory effect of S-342-3 on biofilm is achieved by downregulating the expression of genes responsible for biofilm formation. In addition, S-342-3 is non-toxic to Galleria mellonella larvae and A549 cells. Consequently, this study demonstrates the efficacy of a biologically safe compound S-342-3 in inhibiting biofilm formation in S. aureus, thereby providing a promising antibiofilm agent for further research.

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Section: Discussionmentioning

confidence: 99%

A novel small-molecule compound S-342-3 effectively inhibits the biofilm formation of Staphylococcus aureus

Zhang,

Shen,

Zhou

et al. 2023

Microbiol Spectr

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“…For antibiofilm formation activity, geraniol and camphor exhibited antibiofilm activity by inhibiting S. aureus biofilm with the inhibition percentage of 86.13 ± 5.22 and 81.25 ± 1.63 after exposure to 256 µ g/mL of geraniol and 10 mg/mL of camphor, respectively [ 41 , 42 ]. Furthermore, Vijayakumar et al [ 43 ] found that eucalyptol showed a concentration-dependent manner for inhibition of biofilm formation of Streptococcus pyogenes by 89% inhibition after exposure to this chemical at a concentration of 300 µ g/mL.…”

Section: Discussionmentioning

confidence: 99%

Synergistic Interaction between Boesenbergia rotunda (L.) Mansf. Essential Oil and Cloxacillin on Methicillin‐Resistant Staphylococcus aureus (MRSA) Inhibition

Apinundecha

Teethaisong

Suknasang

et al. 2023

Evidence-Based Complementary and Alternative Medicine

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Currently, antibiotic resistance is widespread among bacteria. This problem requires greater awareness because bacterial resistance increases, reducing antibiotic use effectiveness. Consequently, new alternative treatments are needed because the treatment options for these bacteria are limited. This work aims to determine the synergistic interaction and mechanism of action of Boesenbergia rotunda essential oil (BREO) against methicillin-resistant Staphylococcus aureus (MRSA). Gas chromatography-mass spectrometry identified 24 BREO chemicals (GC-MS). The main components of BREO were β-ocimene (36.73%), trans-geraniol (25.29%), camphor (14.98%), and eucalyptol (8.99%). BREO and CLX inhibited MRSA DMST 20649, 20651, and 20652 with a minimum inhibitory concentration (MIC) of 4 mg/mL and 512 µg/mL, respectively. The checkerboard method and the time-kill assay revealed synergy between BREO and CLX with fractional inhibitory concentration (FIC) <0.5 and log reduction >2log10 CFU/mL at 24 hours compared to the most effective chemical. BREO inhibited biofilm formation and increased membrane permeability. Exposure alone to BREO or in combination with CLX inhibited biofilm formation and increased cytoplasmic membrane (CM) permeability. The scanning electron microscopy (SEM) and transmission electron microscopy (TEM) results revealed that alterations in the cell walls, cytoplasmic membrane, and leakage of intracellular components of MRSA DMST 20651 after treatment with BREO alone and in combination with CLX were observed. These results indicate that BREO synergizes and could reverse the antibacterial activity of CLX against MRSA strains. The synergy of BREO may lead to novel drug combinations that increase the effectiveness of antibiotics against MRSA.

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“…This result was in accordance with previous reports that many natural compounds were able to destroy the structure of biofilm. For instance, Gu et al (2022) observed the biofilm of S. aureus USA300 on slides decreased as the concentration of geraniol increased. The morphological changes of S. aureus biofilm treated with punicalagin was also confirmed by CLSM.…”

Section: Discussionmentioning

confidence: 99%

Antibiofilm effects of punicalagin against Staphylococcus aureus in vitro

Guo

Luo

et al. 2023

Front. Microbiol.

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Staphylococcus aureus is a common foodborne pathogen which can form biofilms to help them resist to antimicrobials. It brings great harm to human health. Punicalagin has good antimicrobial activities against S. aureus, but its effect on biofilm formation has not been clearly illustrated. The aim of this study was to explore the antibiofilm effects of punicalagin against S. aureus. Results showed that punicalagin did not significantly interfere with the growth of S. aureus at the concentrations of 1/64 MIC to 1/16 MIC. The biomass and metabolic activity of biofilms were significantly reduced when exposed to sub-inhibitory concentrations of punicalagin. The number of viable cells in the biofilms was also decreased after punicalagin treatment. Scanning electron microscopy and confocal laser scanning microscopy images confirmed that punicalagin damaged the structure of biofilms. The antibiofilm mechanism was partly due to the modification of the cell surface which led to the reduction of cell surface hydrophobicity. These findings suggest that punicalagin has the potential to be developed as an alternative to control S. aureus biofilms.

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

Cited by 12 publications

References 56 publications

A novel small-molecule compound S-342-3 effectively inhibits the biofilm formation of Staphylococcus aureus

A novel small-molecule compound S-342-3 effectively inhibits the biofilm formation of Staphylococcus aureus

Synergistic Interaction between Boesenbergia rotunda (L.) Mansf. Essential Oil and Cloxacillin on Methicillin‐Resistant Staphylococcus aureus (MRSA) Inhibition

Antibiofilm effects of punicalagin against Staphylococcus aureus in vitro

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