scholarly journals Anandamide alters the membrane properties, halts the cell division and prevents drug efflux in multidrug resistant Staphylococcus aureus

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shreya Banerjee ◽  
Ronit Vogt Sionov ◽  
Mark Feldman ◽  
Reem Smoum ◽  
Raphael Mechoulam ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Division ◽  
Nile Red ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Membrane Properties ◽  
Drug Efflux ◽  
Membrane Structures ◽  
Bacterial Membranes ◽  
Dose Dependent

AbstractAntibiotic resistance is a serious public health problem throughout the world. Overcoming methicillin and multidrug-resistant Staphylococcus aureus (MRSA/MDRSA) infections has become a challenge and there is an urgent need for new therapeutic approaches. We have previously demonstrated that the endocannabinoid Anandamide (AEA) can sensitize MRSA to antibiotics. Here we have studied the mechanism of action using a MDRSA clinical isolate that are sensitized by AEA to methicillin and norfloxacin. We found that AEA treatment halts the growth of both antibiotic-sensitive and antibiotic-resistant S. aureus. The AEA-treated bacteria become elongated and the membranes become ruffled with many protrusions. AEA treatment also leads to an increase in the percentage of bacteria having a complete septum, suggesting that the cell division is halted at this stage. The latter is supported by cell cycle analysis that shows an accumulation of bacteria in the G2/M phase after AEA treatment. We further observed that AEA causes a dose-dependent membrane depolarization that is partly relieved upon time. Nile red staining of the bacterial membranes indicates that AEA alters the membrane structures. Importantly, 4′-6-diamidino-2-phenylindole (DAPI) accumulation assay and ethidium bromide efflux (EtBr) assay unveiled that AEA leads to a dose-dependent drug accumulation by inhibiting drug efflux. In conclusion, our study demonstrates that AEA interferes with cell division, alters the membrane properties of MDRSA, and leads to increased intracellular drug retention, which can contribute to the sensitization of MDRSA to antibiotics.

scholarly journals Anti-Bacterial Properties of Cannabigerol Toward Streptococcus mutans

2021 ◽  
Vol 12 ◽  
Author(s):  
Muna Aqawi ◽  
Ronit Vogt Sionov ◽  
Ruth Gallily ◽  
Michael Friedman ◽  
Doron Steinberg
Keyword(s):  
Electron Microscopy ◽  
Streptococcus Mutans ◽  
Nile Red ◽  
Membrane Properties ◽  
Physiological Adaptation ◽  
Membrane Structures ◽  
Iodide Uptake ◽  
Gram Positive ◽  
Membrane Hyperpolarization ◽  
Acid Tolerant

Streptococcus mutans (S. mutans) is a gram-positive facultatively anaerobic bacterium and the most common pathogen associated with tooth caries. The organism is acid tolerant and can undergo physiological adaptation to function effectively in acid environments such as carious dental plaque. Some cannabinoids have been found to have potent anti-microbial activity against gram-positive bacteria. One of these is the non-psychoactive, minor phytocannabinoid Cannabigerol (CBG). Here we show that CBG exhibits anti-bacterial activities against S. mutans. CBG halts the proliferation of planktonic growing S. mutans, which is affected by the initial cell density. High-resolution scanning electron microscopy showed that the CBG-treated bacteria become swollen with altered membrane structures. Transmission electron microscopy provided data showing that CBG treatment leads to intracellular accumulation of membrane structures. Nile red, DiOC2(3) and laurdan staining demonstrated that CBG alters the membrane properties, induces membrane hyperpolarization, and decreases the membrane fluidity. CBG-treated bacteria showed increased propidium iodide uptake and reduced calcein AM staining, suggesting that CBG increases the membrane permeability and reduces the metabolic activity. Furthermore, CBG prevented the drop in pH caused by the bacteria. In summary, we present here data showing the mechanisms by which CBG exerts its anti-bacterial effect against S. mutans.

scholarly journals Curcumin-loaded graphene oxide flakes as an effective antibacterial system against methicillin-resistant Staphylococcus aureus

2018 ◽  
Vol 8 (3) ◽  
pp. 20170059 ◽  
Author(s):  
F. Bugli ◽  
M. Cacaci ◽  
V. Palmieri ◽  
R. Di Santo ◽  
R. Torelli ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Graphene Oxide ◽  
Drug Loading ◽  
Water Environment ◽  
Antibacterial Properties ◽  
Public Health Problem ◽  
Major Constituent ◽  
Global Public Health ◽  
Methicillin Resistant ◽  
Bacterial Membranes

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for serious hospital infections worldwide and represents a global public health problem. Curcumin, the major constituent of turmeric, is effective against MRSA but only at cytotoxic concentrations or in combination with antibiotics. The major issue in curcumin-based therapies is the poor solubility of this hydrophobic compound and the cytotoxicity at high doses. In this paper, we describe the efficacy of a composite nanoparticle made of curcumin (CU) and graphene oxide (GO), hereafter GOCU, in MRSA infection treatment. GO is a nanomaterial with a large surface area and high drug-loading capacity. GO has also antibacterial properties due mainly to a mechanical cutting of the bacterial membranes. For this physical mechanism of action, microorganisms are unlikely to develop resistance against this nanomaterial. In this work, we report the capacity of GO to support and stabilize curcumin molecules in a water environment and we demonstrate the efficacy of GOCU against MRSA at a concentration below 2 µg ml −1 . Further, GOCU displays low toxicity on fibroblasts cells and avoids haemolysis of red blood cells. Our results indicate that GOCU is a promising nanomaterial against antibiotic-resistant MRSA.

scholarly journals New Mechanism of Magnolol and Honokiol from Magnolia officinalis against Staphylococcus aureus

2014 ◽  
Vol 9 (9) ◽  
pp. 1934578X1400900 ◽  
Author(s):  
Tao Liu ◽  
Yalin Pan ◽  
Renfu Lai
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Division ◽  
Antimicrobial Agents ◽  
Inhibitory Concentration ◽  
Multidrug Resistant ◽  
Binding Energies ◽  
Methicillin Resistant ◽  
Computer Aided ◽  
Cell Division Protein ◽  
Magnolia Officinalis

Cell division protein, FtsZ, has been identified as a new potential antimicrobial target against multidrug-resistant (MDR) and methicillin-resistant Staphylococcus aureus (MRSA). By using computer-aided simulation, the phenolic compounds magnolol and honokiol from Magnolia officinalis were shown to have high anchor energies to FtsZ of S.aureus. The calculated binding energies of magnolol and honokiol for this FtsZ (PDB Code: 4DXD) were established to be −7.6 kcal/mol and −8.2 kcal/mol, respectively. Both of them showed polymerization inhibition efficacy for this FtsZ at 100 ppm, which confirmed the simulation results. Their antibacterial activity against S. aureus including multidrug-resistant (MDR) and methicillin-resistant S.aureus (MRSA) with minimum inhibitory concentration (MIC) values in the range of 8–16 ppm. These findings support the use of computer-aided simulation to screen natural compounds for this cell division protein, FtsZ, and this method can be a quick and promising approach for the development of antimicrobial agents against multi-drug resistant S. aureus.

scholarly journals Membrane-Targeting Triphenylphosphonium Functionalized Ciprofloxacin for Methicillin-Resistant Staphylococcus aureus (MRSA)

Antibiotics ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 758
Author(s):  
Sangrim Kang ◽  
Kyoung Sunwoo ◽  
Yuna Jung ◽  
Junho K. Hur ◽  
Ki-Ho Park ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Morphological Changes ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Severe Problem ◽  
Methicillin Resistant ◽  
Bacterial Membranes ◽  
High Antibacterial Activity ◽  
New Antibiotics

Multidrug-resistant (MDR) bacteria have become a severe problem for public health. Developing new antibiotics for MDR bacteria is difficult, from inception to the clinically approved stage. Here, we have used a new approach, modification of an antibiotic, ciprofloxacin (CFX), with triphenylphosphonium (TPP, PPh3) moiety via ester- (CFX-ester-PPh3) and amide-coupling (CFX-amide-PPh3) to target bacterial membranes. In this study, we have evaluated the antibacterial activities of CFX and its derivatives against 16 species of bacteria, including MDR bacteria, using minimum inhibitory concentration (MIC) assay, morphological monitoring, and expression of resistance-related genes. TPP-conjugated CFX, CFX-ester-PPh3, and CFX-amide-PPh3 showed significantly improved antibacterial activity against Gram-positive bacteria, Staphylococcus aureus, including MDR S. aureus (methicillin-resistant S. aureus (MRSA)) strains. The MRSA ST5 5016 strain showed high antibacterial activity, with MIC values of 11.12 µg/mL for CFX-ester-PPh3 and 2.78 µg/mL for CFX-amide-PPh3. The CFX derivatives inhibited biofilm formation in MRSA by more than 74.9% of CFX-amide-PPh3. In the sub-MIC, CFX derivatives induced significant morphological changes in MRSA, including irregular deformation and membrane disruption, accompanied by a decrease in the level of resistance-related gene expression. With these promising results, this method is very likely to combat MDR bacteria through a simple TPP moiety modification of known antibiotics, which can be readily prepared at clinical sites.

Modulation of the drug resistance by Platonia insignis Mart. extract, ethyl acetate fraction and Morelloflavone/Volkensiflavone (biflavonoids) in Staphylococcus aureus strains overexpressing efflux pump genes

2020 ◽  
Vol 21 ◽  
Author(s):  
Andressa Kelly Ferreira e Silva ◽  
Antonielly Campinho dos Reis ◽  
Emanuelly Elanny Andrade Pinheiroc ◽  
Jonas Nascimento de Sousa ◽  
Felipe Araújo de Alcântara Oliveira ◽  
...  
Keyword(s):  
Natural Products ◽  
Ethyl Acetate ◽  
Native Species ◽  
Efflux Pump ◽  
Public Health Problem ◽  
Ethyl Acetate Fraction ◽  
Multidrug Resistant ◽  
Global Public Health ◽  
Minimal Inhibitory Concentrations ◽  
Subinhibitory Concentrations

Background: Microbial resistance to antibiotics is a global public health problem, which requires urgent attention. Platonia insignis is a native species from the eastern Brazilian Amazon, used in the treatment of burns and wounds. Objectives: To evaluate the antimicrobial activity of the hydroalcoholic extract of P. insignis (PIHA), the ethyl acetate fraction (PIAE), and its subfraction containing a mixture of biflavonoids (BF). Moreover, the effect of these natural products on the antibiotic activity against S. aureus strains overexpressing efflux pump genes was also evaluated. Methods: Minimal inhibitory concentrations were determined against different species of microorganisms. To evaluate the modulatory effect on the Norfloxacin-resistance, the MIC of this antibiotic was determined in the absence and presence of the natural products at subinhibitory concentrations. Inhibition of the EtBr efflux assays were conducted in the absence or presence of the natural products. Results: PIHA showed a microbicidal effect against S. aureus and C. albicans, while PIAE was bacteriosctatic for S. aureus. PIAE and BF at subinhibitory concentrations were able to reduce the MIC of Norfloxacin acting as modulating agents. BF was able to inhibit the efflux of EtBr efflux in S. aureus strains overexpressing specific efflux pump genes. Conclusion: P. inignisis a source of efflux pump inhibitors, including volkensiflavone and morelloflavone which were able to potentiate the Norfloxacin activity by NorA inhibition, being also able to inhibit QacA/B, TetK and MsrA. Volkensiflavone and morelloflavone could be used as adjuvant in the antibiotic therapy of multidrug resistant S. aureus strains overexpressing efflux pumps.

Biological Evaluation of Selected 1,2,3-triazole Derivatives as Antibacterial and Antibiofilm Agents

2020 ◽  
Vol 20 (24) ◽  
pp. 2186-2191
Author(s):  
Lialyz Soares Pereira André ◽  
Renata Freire Alves Pereira ◽  
Felipe Ramos Pinheiro ◽  
Aislan Cristina Rheder Fagundes Pascoal ◽  
Vitor Francisco Ferreira ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Staphylococcus Aureus ◽  
Biofilm Formation ◽  
Antimicrobial Agents ◽  
Public Health Problem ◽  
Biological Evaluation ◽  
Major Public Health Problem ◽  
Community Environments ◽  
Scanning Electron

Background: Resistance to antimicrobial agents is a major public health problem, being Staphylococcus aureus prevalent in infections in hospital and community environments and, admittedly, related to biofilm formation in biotic and abiotic surfaces. Biofilms form a complex and structured community of microorganisms surrounded by an extracellular matrix adhering to each other and to a surface that gives them even more protection from and resistance against the action of antimicrobial agents, as well as against host defenses. Methods: Aiming to control and solve these problems, our study sought to evaluate the action of 1,2,3- triazoles against a Staphylococcus aureus isolate in planktonic and in the biofilm form, evaluating the activity of this triazole through Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) tests. We have also performed cytotoxic evaluation and Scanning Electron Microscopy (SEM) of the biofilms under the treatment of the compound. The 1,2,3-triazole DAN 49 showed bacteriostatic and bactericidal activity (MIC and MBC 128 μg/mL). In addition, its presence interfered with the biofilm formation stage (1/2 MIC, p <0.000001) and demonstrated an effect on young preformed biofilm (2 MICs, p <0.05). Results: Scanning Electron Microscopy images showed a reduction in the cell population and the appearance of deformations on the surface of some bacteria in the biofilm under treatment with the compound. Conclusion: Therefore, it was possible to conclude the promising anti-biofilm potential of 1,2,3-triazole, demonstrating the importance of the synthesis of new compounds with biological activity.

scholarly journals Nearly Identical Plasmids Encoding VIM-1 and Mercury Resistance in Enterobacteriaceae from North-Eastern Germany

2021 ◽  
Vol 9 (7) ◽  
pp. 1345
Author(s):  
Stefan E. Heiden ◽  
Katharina Sydow ◽  
Stephan Schaefer ◽  
Ingo Klempien ◽  
Veronika Balau ◽  
...  
Keyword(s):  
Resistance Gene ◽  
Bacterial Species ◽  
Genomic Analysis ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Mercury Resistance ◽  
Major Public Health Problem ◽  
Eastern Germany ◽  
North Eastern ◽  
Resistance Plasmids

The emergence of carbapenemase-producing Enterobacteriaceae limits therapeutic options and presents a major public health problem. Resistances to carbapenems are mostly conveyed by metallo-beta-lactamases (MBL) including VIM, which are often encoded on resistance plasmids. We characterized four VIM-positive isolates that were obtained as part of a routine diagnostic screening from two laboratories in north-eastern Germany between June and August 2020. Whole-genome sequencing was performed to address (a) phylogenetic properties, (b) plasmid content, and (c) resistance gene carriage. In addition, we performed phenotypic antibiotic and mercury resistance analyses. The genomic analysis revealed three different bacterial species including C. freundii, E. coli and K. oxytoca with four different sequence types. All isolates were geno- and phenotypically multidrug-resistant (MDR) and the phenotypic profile was explained by the underlying resistance gene content. Three isolates of four carried nearly identical VIM-1-resistance plasmids, which in addition encoded a mercury resistance operon and showed some similarity to two publicly available plasmid sequences from sources other than the two laboratories above. Our results highlight the circulation of a nearly identical IncN-type VIM-1-resistance plasmid in different Enterobacteriaceae in north-eastern Germany.

scholarly journals The Prevalence of Virulence Determinants and Antibiotic Resistance Patterns in Methicillin—Resistant Staphylococcus aureus in a Nursing Home in Poland

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 427
Author(s):  
Martyna Kasela ◽  
Agnieszka Grzegorczyk ◽  
Bożena Nowakowicz-Dębek ◽  
Anna Malm
Keyword(s):  
Staphylococcus Aureus ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Variable Number Tandem Repeat ◽  
Multidrug Resistant ◽  
Variable Number ◽  
Pulse Field ◽  
Virulence Determinants ◽  
Gene Encoding ◽  
Methicillin Resistant ◽  
Pulse Field Gel Electrophoresis

Nursing homes (NH) contribute to the regional spread of methicillin-resistant Staphylococcus aureus (MRSA). Moreover, residents are vulnerable to the colonization and subsequent infection of MRSA etiology. We aimed at investigating the molecular and phenotypic characteristics of 21 MRSA collected from the residents and personnel in an NH (Lublin, Poland) during 2018. All MRSA were screened for 20 genes encoding virulence determinants (sea-see, eta, etb, tst, lukS-F-PV, eno, cna, ebpS, fib, bbp, fnbA, fnbB, icaADBC) and for resistance to 18 antimicrobials. To establish the relatedness and clonal complexes of MRSA in NH we applied multiple-locus variable-number tandem-repeat fingerprinting (MLVF), pulse field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and staphylococcal cassette chromosome mec (SCCmec) typing. We identified four sequence types (ST) among two clonal complexes (CC): ST (CC22) known as EMRSA-15 as well as three novel STs—ST6295 (CC8), ST6293 (CC8) and ST6294. All tested MRSA were negative for sec, eta, etb, lukS-F-PV, bbp and ebpS genes. The most prevalent gene encoding toxin was sed (52.4%; n = 11/21), and adhesins were eno and fnbA (100%). Only 9.5% (n = 2/21) of MRSA were classified as multidrug-resistant. The emergence of novel MRSA with a unique virulence and the presence of epidemic clone EMRSA-15 creates challenges for controlling the spread of MRSA in NH.

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