Antimicrobial and antibiofilm activity and machine learning classification analysis of essential oils from different mediterranean plants against pseudomonas aeruginosa

Pseudomonas aeruginosa is a ubiquitous organism and opportunistic pathogen that can cause persistent infections due to its peculiar antibiotic resistance mechanisms and to its ability to adhere and form biofilm. The interest in the development of new approaches for the prevention and treatment of biofilm formation has recently increased. The aim of this study was to seek new non-biocidal agents able to inhibit biofilm formation, in order to counteract virulence rather than bacterial growth and avoid the selection of escape mutants. Herein, different essential oils extracted from Mediterranean plants were analyzed for their activity againstP. aeruginosa. Results show that they were able to destabilize biofilm at very low concentration without impairing bacterial viability. Since the action is not related to a bacteriostatic/bactericidal activity onP. aeruginosa, the biofilm change of growth in presence of the essential oils was possibly due to a modulation of the phenotype. To this aim, application of machine learning algorithms led to the development of quantitative activity-composition relationships classification models that allowed to direct point out those essential oil chemical components more involved in the inhibition of biofilm production. The action of selected essential oils on sessile phenotype make them particularly interesting for possible applications such as prevention of bacterial contamination in the community and in healthcare environments in order to prevent human infections. We assayed 89 samples of different essential oils asP. aeruginosaanti-biofilm. Many samples inhibitedP. aeruginosabiofilm at concentrations as low as 48.8 µg/mL. Classification of the models was developed through machine learning algorithms

Essential oils biofilm modulation activity, chemical and machine learning analysis. Application on staphylococcus aureus isolates from cystic fibrosis patients

Bacterial biofilm plays a pivotal role in chronic Staphylococcus aureus (S. aureus) infection and its inhibition may represent an important strategy to develop novel therapeutic agents. The scientific community is continuously searching for natural and “green alternatives” to chemotherapeutic drugs, including essential oils (EOs), assuming the latter not able to select resistant strains, likely due to their multicomponent nature and, hence, multitarget action. Here it is reported the biofilm production modulation exerted by 61 EOs, also investigated for their antibacterial activity on S. aureus strains, including reference and cystic fibrosis patients’ isolated strains. The EOs biofilm modulation was assessed by Christensen method on five S. aureus strains. Chemical composition, investigated by GC/MS analysis, of the tested EOs allowed a correlation between biofilm modulation potency and putative active components by means of machine learning algorithms application. Some EOs inhibited biofilm growth at 1.00% concentration, although lower concentrations revealed dierent biological profile. Experimental data led to select antibiofilm EOs based on their ability to inhibit S. aureus biofilm growth, which were characterized for their ability to alter the biofilm organization by means of SEM studies

A Series of COX-2 Inhibitors Endowed with NO-Releasing Properties: Synthesis, Biological Evaluation, and Docking Analysis

Herein we report the synthesis, biological evaluation, and docking analysis of a class of cyclooxygenase-2 (COX-2) inhibitors with nitric oxide (NO)-releasing properties. In an earlier study, a number of selective COX-2 inhibitors/NO donors were developed by conjugating a diarylpyrrole scaffold endowed with selective COX-2 inhibitory properties with various nitrooxyalkyl side chains such as esters, -amino esters, amides, -amino amides, ethers, -amino ethers, inverse esters, and amides. These candidates were found to have high invitro potencies (COX-2 inhibition at 10m: 96%), great efficacy in determining NO-vasorelaxing responses, and good antinociceptive activity in an abdominal writhing test. Among the compounds synthesized in the present work, derivative 2b [2-(2-(1-(3-fluorophenyl)-2-methyl-5-(4-sulfamoylphenyl)-1H-pyrrol-3-yl)acetamido)ethyl nitrate] showed particularly outstanding activity, with efficacy similar to that of celecoxib even at very low concentrations

A first attempt to evaluate the toxicity to Phaeodactylum tricornutum Bohlin exposed to rare earth elements

The increasing use and demand of rare earth elements in many emerging technologies is leading to a potentially higher input to the marine environment. This study compared for the first time the effect of lanthanum (La), cerium (Ce), neodymium (Nd), samarium (Sm), europium (Eu), gadolinium (Gd), dysprosium (Dy), and erbium (Er) to the microalga Phaeodactylum tricornutum Bohlin. The algal growth inhibition was investigated after 72 h of exposure. The median effect concentrations (EC50) ranged from 0.98 mg/L to 13.21 mg/L and elements were ranked as follows: Gd > Ce > Er > La > Eu > Nd > Dy > Sm. The comparison of predicted no effect concentrations (PNEC) for hazard and risk assessment with measured environmental concentrations showed that ecological risks deriving from REEs could be present, but limited to specific environments like estuarine waters. The results support evidence of actions to manage the REE impact in seawater environments, looking to improve the monitoring tailored to the different and dynamic nature of ecosystems

Defence strategies and antibiotic resistance gene abundance in enterococci under stress by exposure to low doses of peracetic acid

partially_open12noPeracetic acid (PAA) is an organic compound used efficiently as disinfectant in wastewater treatments. Yet, at low doses it may cause selection; thus, the effect of low doses of PAA on Enterococcus faecium as a proxy of human-related microbial waste was evaluated. Bacteria were treated with increasing doses of PAA (from 0 to 25 mg L1 min) and incubated in regrowth experiments under non-growing, limiting conditions and under growing, favorable conditions. The changes in bacterial abundance, in bacterial phenotype (number and composition of small cell clusters), and in the abundance of an antibiotic resistance gene (ARG) was evaluated. The experiment demonstrated that the selected doses of PAA efficiently removed enterococci, and induced a long-lasting effect after PAA inactivation. The relative abundance of small clusters increased during the experiment when compared with that of the inoculum. Moreover, under growing favorable conditions the relative abundance of small clusters decreased and the number of cells per cluster increased with increasing PAA doses. A strong stability of the measured ARG was found, not showing any effect during the whole experiment. The results demonstrated the feasibility of low doses of PAA to inactivate bacteria. However, the stress induced by PAA disinfection promoted a bacterial adaptation, even if potentially without affecting the abundance of the ARG.openTurolla, Andrea; Sabatino, Raffaella; Fontaneto, Diego; Eckert, Ester M.; Colinas, Noemi; Corno, Gianluca; Citterio, Barbara; Biavasco, Francesca; Antonelli, Manuela; Mauro, Alessandro; Mangiaterra, Gianmarco; Di Cesare, AndreaTurolla, Andrea; Sabatino, Raffaella; Fontaneto, Diego; Eckert, Ester M.; Colinas, Noemi; Corno, Gianluca; Citterio, Barbara; Biavasco, Francesca; Antonelli, Manuela; Mauro, Alessandro; Mangiaterra, Gianmarco; Di Cesare, Andre

Composition of the Essential Oil of Coristospermum cuneifolium and Antimicrobial Activity Evaluation

AbstractFor the first time, the chemical composition and antimicrobial evaluation of Coristospermum cuneifolium (previously named Ligusticum lucidum subsp. cuneifolium) essential oil obtained from the aerial parts are reported in this work. Approximately 85% of the total constituents were identified by GC-MS analysis, evidencing the presence of 12 chemical components which belong to several classes of natural compounds. Most of them are reported for the first time in the Ligusticum genus (s.l.) and in the Apiaceae family. Their presence was able to provide a rationale for essential oil use in the field similar to those obtained from other species of the Ligusticum genus (s.l.). Moreover, the huge presence of aromatizing and flavoring components, accounting for 44.4% of the essential oil composition, might make C. cuneifolium a useful natural source of aromatic components for the food and cosmetic fields. In addition to this, a deep comparison of the essential oil of this species with that of other entities within the Ligusticum genus (s.l.) was performed and discussed on a chemotaxonomic basis.The essential oil was tested for its antimicrobial activity at both high and low inoculum (~5×105 and ~ 5×103 cfu/mL, respectively) against several bacterial and fungal strains, including methicillin-susceptible Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), Candida albicans (ATCC 14053), methicillin-resistant S. aureus (clinical strain), carbapenem-susceptible Klebsiella pneumoniae (clinical strain), carbapenem-resistant K. pneumoniae (clinical strain), and carbapenem-resistant Acinetobacter baumannii (clinical strain).A high potency against C. albicans was shown, with an absence of growth at the concentration of 3.01 mg/mL; similarly, for methicillin-susceptible S. aureus and methicillin-resistant S. aureus, a reduction of 1.73 and 2 log10 cfu/mL at the concentration of 3.01 mg/mL was observed. With regard to gram-negative microorganisms, only slight potency against A. baumannii was shown, whereas no activity was found against E. coli and K. pneumoniae

Synthesis, biological evaluation and docking analysis of a new series of methylsulfonyl and sulfamoyl acetamides and ethyl acetates as potent COX-2 inhibitors

We report herein the synthesis, biological evaluation and docking analysis of a new series of methylsulfonyl, sulfamoyl acetamides and ethyl acetates that selectively inhibit cyclooxygenase-2 (COX-2) isoform. Among the newly synthesized compounds, some of them were endowed with a good activity against COX-2 and a good selectivity COX-2/COX-1 in vitro as well as a desirable analgesic activity in vivo, proving that replacement of the ester moiety with an amide group gave access to more stable derivatives, characterized by a good COX-inhibition

Identification of Inhibitors to trypanosoma cruzi sirtuins based on compounds developed to human enzymes

Chagas disease is an illness caused by the protozoan parasite Trypanosoma cruzi, affecting more than 7 million people in the world. Benznidazole and nifurtimox are the only drugs available for treatment and in addition to causing several side effects, are only satisfactory in the acute phase of the disease. Sirtuins are NAD+-dependent deacetylases involved in several biological processes, which have become drug target candidates in various disease settings. T. cruzi presents two sirtuins, one cytosolic (TcSir2rp1) and the latter mitochondrial (TcSir2rp3). Here, we characterized the effects of human sirtuin inhibitors against T. cruzi sirtuins as an initial approach to develop specific parasite inhibitors. We found that, of 33 compounds tested, two inhibited TcSir2rp1 (15 and 17), while other five inhibited TcSir2rp3 (8, 12, 13, 30, and 32), indicating that specific inhibitors can be devised for each one of the enzymes. Furthermore, all inhibiting compounds prevented parasite proliferation in cultured mammalian cells. When combining the most effective inhibitors with benznidazole at least two compounds, 17 and 32, demonstrated synergistic effects. Altogether, these results support the importance of exploring T. cruzi sirtuins as drug targets and provide key elements to develop specific inhibitors for these enzymes as potential targets for Chagas disease treatment

Potent In Vitro Activity of Citrus aurantium Essential Oil and Vitis vinifera Hydrolate Against Gut Yeast Isolates from Irritable Bowel Syndrome Patients\u2014The Right Mix for Potential Therapeutic Use

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