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Mode of action of different classes of antibiotics with their resistance profiles and target bacteria.
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Despite the discovery and development of an array of antimicrobial agents, multidrug resistance poses a major threat to public health and progressively increases mortality. Recently, several studies have focused on developing promising solutions to overcome these problems. This has led to the development of effective alternative methods of controll...
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... To our knowledge, this is the first study to analyse the effect of cinnamon and clove EOs on enrofloxacin used to control APEC strains in poultry. The synergy between other antibiotics and essential oils has been well documented [69][70][71]. ...
Avian pathogenic Escherichia coli (APEC) causes a variety of infections outside the intestine. The treatment of these infections is becoming increasingly difficult due to the emergence of multi-drug resistant (MDR) strains, which can also be a direct or indirect threat to humans as consumers of poultry products. Therefore, alternative antimicrobial agents are being sought, which could be essential oils, either administered individually or in interaction with antibiotics. Sixteen field isolates of E. coli (originating from 1-day-old broilers) and the ATCC 25922 reference strain were tested. Commercial cinnamon bark, clove bud, lavender flower essential oils (EOs) and enrofloxacin were selected to assess the sensitivity of the selected E. coli strains to antimicrobial agents. The checkerboard method was used to estimate the individual minimum inhibitory concentration (MIC) for each antimicrobial agent as well as to determine the interactions between the selected essential oil and enrofloxacin. In the case of enrofloxacin, ten isolates were resistant at MIC ≥ 2 μg/mL, three were classified as intermediate (0.5–1 μg/mL) and three as sensitive at ≤0.25 μg/mL. Regardless of the sensitivity to enrofloxacin, the MIC for cinnamon EO was 0.25% v/v and for clove EO was 0.125% v/v. All MDR strains had MIC values for lavender EO of 1% v/v, while drug-sensitive isolates had MIC of 0.5% v/v. Synergism between enrofloxacin and EO was noted more frequently in lavender EO (82.35%), followed by cinnamon EO (64.7%), than in clove EO (47.1%). The remaining cases exhibited additive effects. Owing to synergy, the isolates became susceptible to enrofloxacin at an MIC of ≤8 µg/mL. A time–kill study supports these observations. Cinnamon and clove EOs required for up to 1 h and lavender EO for up to 4 h to completely kill a multidrug-resistant strain as well as the ATCC 25922 reference strain of E. coli. Through synergistic or additive effects, blends with a lower than MIC concentration of enrofloxacin mixed with a lower EO content required 6 ± 2 h to achieve a similar effect.
... The antibacterial qualities of essential oils, for example, have been the focus of much research due to their ability to combat common human diseases [44,45]. Their antibacterial capabilities can be strengthened by mixing them with other substances, such as essential oils and medicines [46]. To determine the effectiveness of O. compactum and O. elongatum essential oils in preventing infection, we developed cultures of bacteria that were resistant to several drugs. ...
The irrational use of antibiotics has favored the emergence of resistant bacteria, posing a serious threat to global health. To counteract antibiotic resistance, this research seeks to identify novel antimicrobials derived from essential oils that operate through several mechanisms. It aims to evaluate the quality and composition of essential oils from Origanum compactum and Origanum elongatum; test their antimicrobial activity against various strains; explore their synergies with commercial antibiotics; predict the efficacy, toxicity, and stability of compounds; and understand their molecular interactions through docking and dynamic simulations. The essential oils were extracted via hydrodistillation from the flowering tops of oregano in the Middle Atlas Mountains in Morocco. Gas chromatography combined with mass spectrometry (GC-MS) was used to examine their composition. Nine common antibiotics were chosen and tested alone or in combination with essential oils to discover synergistic effects against clinically important and resistant bacterial strains. A comprehensive in silico study was conducted, involving molecular docking and molecular dynamics simulations (MD). O. elongatum oil includes borneol (8.58%), p-cymene (42.56%), thymol (28.43%), and carvacrol (30.89%), whereas O. compactum oil is mostly composed of γ-terpinene (22.89%), p-cymene (15.84%), thymol (10.21%), and (E)-caryophyllene (3.63%). With O. compactum proving to be the most potent, these essential oils showed antibacterial action against both Gram-positive and Gram-negative bacteria. Certain antibiotics, including ciprofloxacin, ceftriaxone, amoxicillin, and ampicillin, have been shown to elicit synergistic effects. To fight resistant bacteria, the essential oils of O. compactum and O. elongatum, particularly those high in thymol and (E)-caryophyllene, seem promising when combined with antibiotics. These synergistic effects could result from their ability to target the same bacterial proteins or facilitate access to target sites, as suggested by molecular docking simulations. Molecular dynamics simulations validated the stability of the examined protein–ligand complexes, emphasizing the propensity of substances like thymol and (E)-caryophyllene for particular target proteins, opening the door to potentially effective new therapeutic approaches against pathogens resistant to multiple drugs.
... Antimicrobial products in medical, industrial and household settings often contain multiple disinfectants, with the synergistic effect being a key mechanism. The synergistic combination of antimicrobials broadens the spectrum of antimicrobial action and prevents the emergence of resistant strains (Basavegowda and Baek, 2022). Combining antimicrobial agents reduces toxicity and provides long-lasting residual effects. ...
... Furthermore, the antimicrobial activity of nanoparticles has been attributed to three main mechanisms of action, including (i) adhesion onto the outer membrane, accumulation in the inner membrane, increase in membrane permeability, leakage of cell content followed by cell death; (ii) interaction with sulfur and phosphate groups of the DNA (deoxyribonucleic acid) and proteins to alter their functions; and (iii) interaction with cellular components to alter the metabolic pathways, membranes, and genetic material, among others [39,40,64,65]. ...
Caused by pathogenic microorganisms, infectious diseases are known to cause high
mortality rates, severe burdens of disability, and serious worldwide aftermaths. Drug-resistant
pathogens have reduced the efficacy of available therapies against these diseases, thus accentuating
the need to search for effective antimicrobials. Medicinal plants have served as starting material for
the preparation of a number of antimicrobial agents. To this end, the present study highlights the
green synthesis of Cocos nucifera-based nanomaterials and evaluation of the mechanistic basis of their
antimicrobial action. Accordingly, Cocos nucifera extract was used for the reduction of silver nitrate
solution to afford silver nanoparticles. These entities were further incorporated onto sulfuric-acidbased
activated carbons to generate the nanocomposites. The antimicrobial activity of the as-prepared
nanomaterials was evaluated using the broth microdilution method, while the antioxidant activity
was assessed through standard methods. The cytotoxicity of potent nanomaterials was assessed on
Vero cells by the spectrophotometric method. As a result, nanoparticles were successfully synthesized,
as evidenced by the ultraviolet–visible spectroscopy analysis that revealed an intense absorption
spectrum at 433 nm. Fourier Transform Infrared Spectroscopy presented the functional group moieties
involved as a capping and reducing agent in the synthesis of the nanomaterials. The incubation of
nanomaterials with selected bacterial and fungal strains has led to significant inhibitory effects of these
pathogens with minimum inhibitory concentrations ranging from 7.813 to 250 μg/mL. In antioxidant
assays, the nanocomposites presented scavenging activities comparable to those of ascorbic acid.
Cytotoxicity experiment revealed no toxic effects on Vero cells (range of selectivity indices: from >4 to
>128). These results provide evidence of the implication of Cocos nucifera-based nanomaterials in
targeting bacterial or fungal systems that mediate free-radical damage or by inhibiting the oxidative
damage caused by selected bacteria and fungi, the most susceptible being Escherichia coli and Candida
albicans, respectively.
... Although the two antibiotics alone appeared to have an ineffective anti-biofilm activity at low concentrations tested for the major of isolates, here the in vitro data obtained suggested that the use of cefiderocol in combination with imipenem is a promising therapeutic strategy against P. aeruginosa biofilms, confirming the synergistic activity of the two molecules already observed by the authors in a previous published case report [29]. In fact, the antibiotic combination can achieve therapeutic efficacy with a higher probability and selectivity than drugs administered singularly [30]. ...
... Notably, research has demonstrated potent activity of the bioactive constituents of AI leaf extract against various microbes, including antibiotic resistant bacterial strains. Though plant leaf extracts alone can be used as antimicrobial agents for the treatment of infections, these antimicrobials are not very effective against acute infections because in majority of the cases they lack a standardized and clinically applicable pharmaceutical form [26]. The use of formulations based on purified phytochemicals is not economically viable. ...
... Further, various studies based on animal models and clinical trials indicate that, though the neem plant-derived extract is safe at certain doses, on the other hand, neem and its ingredients showed toxic or adverse effects [27]. Consequently, the combination of plant extracts with different antimicrobials has been considered a unique strategy in increasing the spectrum of antimicrobial activity and preventing the development of resistant strains [26]. ...
With the rise in microbial resistance to traditional antibiotics and disinfectants, there is a pressing need for the development of novel and effective antibacterial agents. Two major approaches being adopted worldwide to overcome antimicrobial resistance are use of plant leaf extracts and metallic nanoparticles, but there is no report on the antibacterial potential of plant extract coated nano particles, which may lead to novel ways of treating infections. This study presents an innovative approach to engineer antibacterial nanoparticles by leveraging the inherent antibacterial properties of Zinc Oxide nanoparticles (ZnO NPs) in combination with Azadirachta indica (AI) leaf extract, resulting in enhanced antibacterial efficacy. ZnO NPs were synthesized by precipitation method and subsequently coated with AI leaf extract to produce ZnO-AI nanocore-shell structures. The structural and morphological characteristics of the bare and leaf extract coated ZnO NPs were analysed by x-ray diffraction (XRD) and field emission scanning electron microscopy (FESEM), respectively. Confirmation of coating of AI leaf extract onto ZnO NPs and subsequent formation of ZnO-AI nanocore-shell structures was accomplished through Fourier transform infrared (FTIR) spectroscopy and photoluminescence (PL) techniques. The antibacterial efficacy of both ZnO NPs and ZnO-AI nanocore-shell particles were evaluated against Methicillin-Resistant Staphylococcus aureus (MRSA) using zone of inhibition assay. The results showed a nanoparticle concentration-dependent increase in the diameter of the inhibition zone, with ZnO-AI nanocore-shell particles exhibiting superior antibacterial properties, owing to the combined effect of ZnO NPs and the poly phenols present in AI leaf extract. These findings suggest ZnO-AI nanocore-shell structures hold promise for the development of novel antibacterial creams and hydrogels for various biomedical applications.
... These applications spread the evolutionary pressure to develop drug resistance across multiple separate molecules. For example, it has been shown that administering multiple drugs can re-sensitize bacteria to drugs and reduce the development of resistance overall [50,51]. The principle of FMN unquenching can even be applied more broadly, in systems outside of FRS, to target FMN-binding proteins in bacteria or humans and may identify compounds with therapeutic effects in diseases other than bacterial infections. ...
Antibiotic resistance remains a pressing global concern, with most antibiotics targeting the bacterial ribosome or a limited range of proteins. One class of underexplored antibiotic targets is bacterial riboswitches, structured RNA elements that regulate key biosynthetic pathways by binding a specific ligand. We developed a methodology termed Fluorescent Ligand Equilibrium Displacement (FLED) to rapidly discover small molecules that bind the flavin mononucleotide (FMN) riboswitch. FLED leverages intrinsically fluorescent FMN and the quenching effect on RNA binding to create a label-free, in vitro method to identify compounds that can bind the apo population of riboswitch in a system at equilibrium. The response difference between known riboswitch ligands and controls demonstrates the robustness of the method for high-throughput screening. An existing drug discovery library that was screened using FLED resulted in a final hit rate of 0.67%. The concentration response of each hit was determined and revealed a variety of approximate effective concentration values. Our preliminary screening data support the use of FLED to identify small molecules for medicinal chemistry development as FMN riboswitch-targeted antibiotic compounds. This robust, label-free, and cell-free method offers a strong alternative to other riboswitch screening methods and can be adapted to a variety of laboratory setups.
... Previous research has shown, for example, the effectiveness of the combination of Eucalyptus globulus essential oil and oxacillin (OXA) against S. aureus, the combination of the extract of Salvadora persica and amoxicillin against Tannerella forsythia and Porphyromonas gingivalis, and the synergy of piperine and ciprofloxacin (CIP) against S. aureus. Researchers have reported various mechanisms of action, involving the modification of efflux pump function, inhibition of enzymatic activity, increased membrane permeability, and unknown mechanisms (Ayaz et al., 2019;Basavegowda and Baek, 2022;Kongkham et al., 2020). In this context, the objective of this review was to assess the available knowledge regarding the combination of ATB with EO and EOC, detailing the methods used in the selected articles (research papers, published after 2016), as well as to compile articles on the dissemination of AMR genes. ...
Antibiotics (ATB) revolutionized medicine, but their overuse has led to antimicrobial resistance (AMR), a major public health crisis. Combining ATBs with essential oils (EO) and their derived compounds (EOC) is a notable option to reduce ATB usage. This combinations lowers the required ATB concentration, addressing resistance issues. This review aims to compile knowledge on ATB-EO/EOC combinations and AMR gene transmission. The articles found indicated that most studies are in vitro, using basic microbiological techniques. These methods, while relevant, don't fully explore combination mechanisms and effects. Furthermore, it was observed that the transmission of resistance genes is extremely common, and a single gene can lead to resistance to multiple drugs, even among ATB exclusively used in animal or human health. AMR is widespread, demanding a multifactorial approach. Combinations offer a potential solution to cut ATB usage, but the pervasive AMR underscores the urgency for innovative technologies to restrict ATB use.
... One promising approach is the use of nanoparticles to improve the delivery of EOs to the bacterial cell wall (Bagheri et al., 2021;Hadidi et al., 2020;Liakos et al., 2018). Another strategy involves the combination of EOs with other antimicrobial agents to create a synergistic effect (Basavegowda & Baek, 2022). ...
Essential oils (EOs) are a class of natural products that exhibit potent antimicrobial properties against a broad spectrum of bacteria. Inhibition diameters (IDs) and minimum inhibitory concentrations (MICs) are the typical measures of antimicrobial activity for extracts and EOs obtained from Cinnamomum, Salvia, and Mentha species. This study used a meta‐analytical regression analysis to investigate the correlation between ID and MIC measurements and the variability in antimicrobial susceptibility tests. By utilizing pooled ID models, this study revealed significant differences in foodborne pathogens’ susceptibility to extracts, which were dependent on both the plant species and the methodology employed (p < .05). Cassia showed the highest efficacy against Salmonella spp., exhibiting a pooled ID of 26.24 mm, while cinnamon demonstrated the highest efficacy against Bacillus cereus, with a pooled ID of 23.35 mm. Mint extract showed the greatest efficacy against Escherichia coli and Staphylococcus aureus. Interestingly, cinnamon extract demonstrated the lowest effect against Shiga toxin‐producing E. coli, with a pooled ID of only 8.07 mm, whereas its EOs were the most effective against this bacterial strain. The study found that plant species influenced the MIC, while the methodology did not affect MIC measurements (p > .05). An inverse correlation between ID and MIC measurements was identified (p < .0001). These findings suggest that extracts and EOs obtained from Cinnamomum, Salvia, and Mentha spp. have the potential to inhibit bacterial growth. The study highlights the importance of considering various factors that may influence ID and MIC measurements when assessing the effectiveness of antimicrobial agents.
... The increased antimicrobial activity of modified TiO 2 can be explained by several mechanisms. First, geraniol ability to adhere to cell membrane lipids of bacteria can mediate antimicrobial activity by increasing the permeabilization of the membrane [62,63]. In addition, the presence of TiO 2 , TiO 2 /anatase/GER, and TiO 2 /rutile/GER can lead to loss of cell wall integrity and direct interaction with DNA leading to cell death [64,65]. ...
Background:
The emergence of antibiotic resistance in pathogenic bacteria has become a global threat, encouraging the adoption of efficient and effective alternatives to conventional antibiotics and promoting their use as replacements. Titanium dioxide nanoparticles (TiO2 NPs) have been reported to exhibit antibacterial properties. In this study, we synthesized and characterized TiO2 NPs in anatase and rutile forms with surface modification by geraniol (GER).
Results:
The crystallinity and morphology of modified TiO2 NPs were analyzed by UV/Vis spectrophotometry, X-ray powder diffraction (XRD), and scanning electron microscopy (SEM) with elemental mapping (EDS). The antimicrobial activity of TiO2 NPs with geraniol was assessed against Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia coli. The minimum inhibitory concentration (MIC) values of modified NPs ranged from 0.25 to 1.0 mg/ml against all bacterial strains, and the live dead assay and fractional inhibitory concentration (FIC) supported the antibacterial properties of TiO2 NPs with GER. Moreover, TiO2 NPs with GER also showed a significant decrease in the biofilm thickness of MRSA.
Conclusions:
Our results suggest that TiO2 NPs with GER offer a promising alternative to antibiotics, particularly for controlling antibiotic-resistant strains. The surface modification of TiO2 NPs by geraniol resulted in enhanced antibacterial properties against multiple bacterial strains, including antibiotic-resistant MRSA. The potential applications of modified TiO2 NPs in the biomedical and environmental fields warrant further investigation.
