The effectiveness of anti-biofilm and anti-virulence properties of dihydrocelastrol and dihydrocelastryl diacetate in fighting against methicillin-resistant Staphylococcus aureus

Abstract

Human pathogens have readily been converted into multidrug-resistant pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), because of the long-term use of conventional antibiotics. In addition, the biofilms formed by S. aureus cells are especially problematic and are related to the persistence of chronic infections because they constitute a major mechanism of promoting tolerance to diverse antimicrobial agents. Hence, the inhibitions of biofilm formation and/or toxin production are accepted as alternative means of controlling S. aureus infections. The present study was aimed at identifying novel anti-biofilm and/or anti-virulence compounds in friedelane-based pentacyclic triterpenoids present in many edible and medicinal plants-and investigating them against MRSA strains. As a result, dihydrocelastrol and dihydrocelastryl diacetate were found to both inhibit the biofilm formation of, and to disrupt the preformed biofilms of, MRSA strains to an increasingly greater degree with increasing concentrations of each compound. Furthermore, these two triterpenoids also clearly inhibited the hemolytic activity of MRSA-and in-line with their anti-biofilm activities, rendered the cell more hydrophilic. Additionally, corroborating phenotypic results, transcriptional analyses showed that both dihydrocelastrol and dihydrocelastryl diacetate disturbed the expression of gene related to α-hemolysin (hla) and down-regulated the expressions of the crucial biofilm-associated genes (agrA, sarA, ica, RNAIII, and rbf) in MRSA. The findings of this study suggest that friedelane-based pentacyclic triterpenoids-especially dihydrocelastrol and dihydrocelastryl diacetate-have the potential to be candidates both for use in controlling biofilm-related infections and for use as important components of anti-virulence strategies for fighting against MRSA infection.

Fungal Extract of Lasiodiplodia pseudotheobromae IBRL OS-64 Inhibits the Growth of Skin Pathogenic Bacterium and Attenuates Biofilms of Methicillin-Resistant Staphylococcus aureus

“…There are many possible mechanisms of the killing action by the extract such as anti-quorum sensing, surface modification mechanism and disruption of crucial genes. For instance, Woo et al ( 38 ) reported the effectiveness of antibiofilm activity of the bioactive compounds, dihydrocelastrol and dihydrocelastryl diacetate. They revealed that both these bioactive compounds were able to down-regulated the expression of crucial genes for biofilm formation, such as RNAIII in MRSA, and disturb the gene expression related to α-hemolysin.…”

Hormonal drugs: Influence on growth, biofilm formation, and adherence of selected gut microbiota

“…The colored solution was measured at wavelength 545 nm. The readings were used to calculate the biofilm formation index ( Kwasny and Opperman, 2010 ; Coffey and Anderson, 2014 ; Woo et al., 2017 ; Jang et al., 2020 ). Five technical replicates were used for each bacterial strain to compensate for variability and three biological replicates were performed.…”

Repurposing auranofin to combat uropathogenic Escherichia coli biofilms

“…Biofilm inhibition assay was performed in 96-well polystyrene plates (BD, Falcon) as previously described (Deziel et al 2001;Woo et al 2017a) with minor modifications. Briefly, bacterial cell suspensions were inoculated into LB medium (total volume 200 ll) containing different concentrations of auranofin (4-48 lg ml À1 ) and incubated at 37°C for 24 h under 5% CO 2 condition.…”

“…Biofilm eradication concentration (BEC) assay was performed to confirm the ability of auranofin to remove preformed biofilm. BEC assay was performed in 96-well polystyrene plates (BD, Falcon) as previously described (Nostro et al 2007;Woo et al 2017a) with some modifications. Briefly, bacterial cell suspension at a concentration of 1 9 10 6 CFU per ml without auranofin treatment was incubated at 37°C for 24 h under 5% CO 2 condition.…”