Promising Antimicrobial Compounds Research Articles

Nisin—A Promising Antimicrobial Compound from Lactic Acid Bacteria

Nisin is a classical bacteriocin consisting of thirty-four amino acid residues and undergoing a high degree of post-translational modification to form a unique pentacyclic structure. Nisin is mainly synthesised by lactic acid bacteria. Under natural conditions, it exhibits strong antibacterial activity against Gram-positive organisms and, when combined with chelating agents, is effective against Gram-negative organisms. An excellent safety profile, low cytotoxicity and slow development of resistance are additional benefits. Currently, the application of nisin is focused on food preservation. This is due to the fact that nisin is naturally present in a wide range of historical fermented foods and its safety is fully guaranteed. With the continuous development of bacterial drug resistance and the consequent demand for new anti-infective drugs, its biomedical applications are being actively explored. However, due to the problems of drug stability, safety, and in vivo activity, there is still a certain distance from clinical application. In this paper, the author summarized the structure, biosynthetic mechanism, applications, and possible research directions of nisin.

Using Machine Learning to Predict the Antibacterial Activity of Ruthenium Complexes.

Rising antimicrobial resistance (AMR) and lack of innovation in the antibiotic pipeline necessitate novel approaches to discovering new drugs. Metal complexes have proven to be promising antimicrobial compounds, but the number of studied compounds is still low compared to the millions of organic molecules investigated so far. Lately, machine learning (ML) has emerged as a valuable tool for guiding the design of small organic molecules, potentially even in low-data scenarios. For the first time, we extend the application of ML to the discovery of metal-based medicines. Utilising 288 modularly synthesized ruthenium arene Schiff-base complexes and their antibacterial properties, a series of ML models were trained. The models perform well and are used to predict the activity of 54 new compounds. These displayed a 5.7x higher hit-rate (53.7 %) against methicillin-resistant Staphylococcus aureus (MRSA) compared to the original library (9.4 %), demonstrating that ML can be applied to improve the success-rates in the search of new metalloantibiotics. This work paves the way for more ambitious applications of ML in the field of metal-based drug discovery.

Maschinelles Lernen zur Vorhersage antibakterieller Aktivität von Ruthenium‐Komplexen**

AbstractDie steigende antimikrobielle Resistenz (AMR) und der Mangel an Innovation in der Antibiotikaforschung erfordern neue Ansätze zur Entwicklung von Medikamenten. Metallkomplexe haben sich als vielversprechende antimikrobielle Verbindungen erwiesen. Allerdings ist die Anzahl der untersuchten Verbindungen noch klein, besonders im Vergleich zu den Millionen organischer Moleküle die bereits getestet wurden. In den letzten Jahren hat sich maschinelles Lernen (ML) als wertvolle Ressource für die Entwicklung organischer Moleküle herauskristallisiert, selbst wenn nur wenige Daten vorliegen. Erstmals erweitern wir die Anwendung von ML auf die Entdeckung von metallbasierten antimikrobiellen Verbindungen. Mithilfe von 288 modular synthetisierten Ruthenium‐Aren‐Schiff‐Basen‐Komplexen und deren antibakteriellen Eigenschaften haben wir eine Reihe von ML–Modellen trainiert. Die Modelle zeigen gute Leistungen und werden verwendet, um die Aktivität von 54 neuen Verbindungen vorherzusagen. Diese Verbindungen weisen eine 5.7‐fach höhere Trefferquote (53.7 %) gegen Methicillin‐resistente Staphylococcus aureus (MRSA) im Vergleich zur ursprünglichen Bibliothek (9.4 %) auf. Dadurch zeigen wir, dass ML zu höheren Erfolgsraten bei der Suche nach neuen Metalloantibiotika führen kann. Folglich ebnet diese Arbeit den Weg für fortschrittlichere Anwendungen von ML im Bereich der metallbasierten Wirkstoffentwicklung.

Antimicrobial and Antioxidant Activity Screening of Mushrooms Growing in the Leningrad Region

Introduction. The emergence of new strains of microorganisms that are multidrug resistant (MDR) in relation to the antimicrobial drugs used is one of the pressing problems of modern medicine. To prevent an increase in MDR-related deaths, the search for new antibiotics and their introduction into medical practice must be continuously ongoing. Infectious diseases are also accompanied by cell damage and the development of free radical oxidation processes, therefore the search for new antioxidants is also an important task. Considering the powerful biosynthetic potential of basidiomycetes, this group of fungi has every prospect of becoming a new source of biologically active substances in general, as well as antibiotics and antioxidants in particular. Cap mushrooms, represented mainly by basidiomycetes, number about 14,000 species and are an accessible source of raw materials for the search for promising antimicrobial compounds and antioxidants.Aim. Study of the antioxidant and antimicrobial activity of total extracts obtained from cap mushrooms against Escherichia coli, Staphylococcus aureus and Candida albicans and assessment of the suitability of cap mushrooms as a natural source of substances with antimicrobial and antioxidant activity.Materials and methods. The antifungal and antibacterial activity of the extracts was determined by the micromethod of two-fold serial dilutions in a liquid nutrient medium in 96-well plates in duplicate. The study of this type of biological activity was carried out against reference (type) strains Staphylococcus aureus ATCC 6538-P, Escherichia coli ATCC 25922, Candida albicans NCTC 885-653. To study antioxidant activity using DPPH, we used alcoholic extracts from the fruiting bodies of mushrooms obtained by maceration with 96 % ethanol at a ratio of raw materials to extractant of 1 to 8 for 24 hours, an aqueous solution of ascorbic acid (vitamin C) and an ethanol solution of Trolox.Result and discussion. In relation to S. aureus, a representative of gram-positive flora, the studied extracts of cap mushrooms showed low activity, on average about 2500 or 5000 μg/ml. In relation to E. coli, a representative of gram-negative flora, 8 % of the studied cap mushroom extracts showed an average activity of about 1250 μg/ml. The largest number of cap mushroom extracts – 19% of all studied species – showed activity against the yeast micromycete C. albicans. The highest activity against C. albicans was observed in extracts of the mushrooms Cantharellula umbonata with an MIC of 625 μg/ml, Cortinarius olivaceofuscus with an MIC of 625 μg/ml, and Hypomyces chrysospermus with an MIC of 312 μg/ml. During screening of antioxidant activity, the studied extracts were divided into three groups: with high (more than 50 % PPR), medium (from 15 to 50 % PPR) and low (less than 15 %) antioxidant activity. It was shown that the sum of phenolic compounds significantly correlates with the level of antioxidant activity in all three groups, but in the groups with medium and low antioxidant activity there are also other non-phenolic groups of compounds that make a significant contribution to the total antioxidant activity.Conclusion. Cap mushrooms are a promising source of biologically active substances with antifungal and antioxidant activity.

Evaluation of Activity of Zinc Oxide Nanoparticles on Human Rotavirus and Multi-Drug Resistant Acinetobacter Baumannii.

Rotaviruses are the cause of acute gastroenteritis and severe diarrheal diseases in children worldwide. Children under the age of five are more susceptible to rotavirus infections. Due to such as the lack of effective drugs and supportive therapy only, the development of new antiviral agents against rotaviruses. Multi-drug-resistant Acinetobacter baumannii is also one of the most challenging Gram-negative bacteria to control and treat due to its antibiotic resistance, particularly in intensive care units. This study aimed to investigate the activity of zinc oxide nanoparticles against human rotavirus and multi-drug resistant Acinetobacter baumannii. The standard 50% tissue culture infectious dose method and the real-time polymerase chain reaction assay were used to investigate the effects of zinc oxide nanoparticles on rotaviruses. The well diffusion and the minimum inhibitory concentration method were used to assess the antibacterial activity of zinc oxide nanoparticles against Acinetobacter baumannii. 300 μg/ml of zinc oxide nanoparticles demonstrated the highest anti-rotavirus effects, resulting in a 3.16 logarithmic decrease in virus infectious titer, and a four-unit increase in the cycle threshold value of the real-time polymerase chain reaction assay compared to the untreated control (P value <0.001 and P value = 0.005, respectively). The diameter of the inhibition zone of zinc oxide nanoparticles solution against Acinetobacter baumannii was 17 mm. The minimum inhibitory concentration results of the zinc oxide nanoparticles solution against Acinetobacter baumannii was 1.56 mg/ml. Our findings showed that zinc oxide nanoparticles could be considered a promising antimicrobial compound.

Antimicrobial, Antibiofilm Activities and Synergic Effect of Triterpene 3β,6β,16β-trihydroxyilup-20(29)-ene Isolated from Combretum leprosum Leaves Against Staphylococcus Strains

Antimicrobial resistance is a natural phenomenon and is becoming a huge global public health problem, since some microorganisms not respond to the treatment of several classes of antibiotics. The objective of the present study was to evaluate the antibacterial, antibiofilm, and synergistic effect of triterpene 3β,6β,16β-trihydroxyilup-20(29)-ene (CLF1) against Staphylococcus aureus and Staphylococcus epidermidis strains. Bacterial susceptibility to CLF1 was evaluated by minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) assay. In addition, the effect combined with antibiotics (ampicillin and tetracycline) was verified by the checkerboard method. The biofilms susceptibility was assessed by enumeration of colony-forming units (CFUs) and quantification of total biomass by crystal violet staining. The compound showed bacteriostatic and bactericidal activity against all Staphylococcal strains tested. The synergistic effect with ampicillin was observed only for S. epidermidis strains. Moreover, CLF1 significantly inhibited the biofilm formation and disrupted preformed biofilm of the all strains. Scanning electron microscopy (SEM) images showed changes in the cell morphology and structure of S. aureus ATCC 700698 biofilms (a methicillin-resistant S. aureus strain). Molecular docking simulations showed that CLF1 has a more favorable interaction energy than the antibiotic ampicillin on penicillin-binding protein (PBP) 2a of MRSA, coupled in different regions of the protein. Based on the results obtained, CLF1 proved to be a promising antimicrobial compound against Staphylococcus biofilms.

Diversity and Antimicrobial Activities of Actinobacteria Isolated from Mining Soils in Midelt Region, Morocco.

Multidrug-resistant bacteria have emerged as a serious global health threat that requires, more than ever before, an urgent need for novel and more effective drugs. In this regard, the present study sheds light on the diversity and antimicrobial potential of Actinobacteria isolates in mining ecosystems. We have indeed investigated the production of bioactive molecules by the Actinobacteria isolated from abandoned mining areas in Midelt, Morocco, where average contents of lead (Pb) and cadmium (Cd) are higher than normal world levels. One hundred and forty-five Actinobacteria isolates were isolated and characterized based on morphological, chemotaxonomical, biochemical, and molecular data. Most of the 145 isolates were identified as Streptomyces. Isolates affiliated to the genera Amycolatopsis, Lentzea, Actinopolymorpha, and Pseudonocardia were also found. Antimicrobial producing potentials of Actinobacteria isolates were assessed against eight test microorganisms Gram+ and Gram- bacteria and yeast. Out of 145 isolates, 51 showed antimicrobial activities against at least one test microorganism. 31 isolates inhibited only bacteria, 7 showed activity against bacteria and Candida albicans, and 13 displayed activity against C. albicans solely. Our findings suggest that Actinobacteria isolated from natural heavy metal ecosystems may be a valuable source of novel secondary metabolites and therefore of new biotechnologically promising antimicrobial compounds.

Antimicrobial Activity of Ceftazidime-Avibactam, Ceftolozane-Tazobactam, Cefiderocol, and Novel Darobactin Analogs against Multidrug-Resistant Pseudomonas aeruginosa Isolates from Pediatric and Adolescent Cystic Fibrosis Patients.

The emergence and spread of antimicrobial resistance (AMR) in Gram-negative pathogens, such as carbapenem-resistant Pseudomonas aeruginosa, pose an increasing threat to health care. Patients with immunodeficiencies or chronic pulmonary disease, like cystic fibrosis (CF), are particularly vulnerable to Pseudomonas infections and depend heavily on antibiotic therapy. To broaden limited treatment options, this study evaluated the potency of the recently licensed drugs ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), and cefiderocol (FDC) as well as two novel preclinical antibiotics, darobactins B (DAR B) and B9 (DAR B9), against clinical P. aeruginosa isolates derived from respiratory samples of CF patients. We observed high levels of resistance to all three newly licensed drugs, with cefiderocol exhibiting the best activity. From the 66 investigated P. aeruginosa isolates, a total of 53% were resistant to CZA, 49% to C/T, and 30% to FDC. Strikingly, 52 of the evaluated isolates were obtained from CF patients prior to market introduction of the drugs. Thus, our results suggest that resistance to CZA, C/T, and FDC may be due to preexisting resistance mechanisms. On the other hand, our two novel preclinical compounds performed better than (CZA and C/T) or close to (FDC) the licensed drugs-most likely due to the novel mode of action. Thus, our results highlight the necessity of global consistency in the area of antibiotic stewardship to prevent AMR from further impairing the potency of antibiotics in clinical practice. Ultimately, this study demonstrates the urgency to support the development of novel antimicrobials, preferably with a new mode of action such as darobactins B and B9, two very promising antimicrobial compounds for the treatment of critically ill patients suffering from multidrug-resistant Gram-negative (MRGN) infections. IMPORTANCE Antimicrobial resistance (AMR) represents an ever increasing threat to the health care system. Even recently licensed drugs are often not efficient for the treatment of infections caused by Gram-negative bacteria, like Pseudomonas aeruginosa, a causative agent of lung infections. To address this unmet medical need, innovative antibiotics, which possess a new mode of action, need to be developed. Here, the antibiogram of clinical isolates derived from cystic fibrosis patients was generated and new bicyclic heptapeptides, which inhibit the outer membrane protein BamA, exhibited strong activity, also against multidrug-resistant isolates.

Gossypol acetate: A natural polyphenol derivative with antimicrobial activities against the essential cell division protein FtsZ.

Antimicrobial resistance has attracted worldwide attention and remains an urgent issue to resolve. Discovery of novel compounds is regarded as one way to circumvent the development of resistance and increase the available treatment options. Gossypol is a natural polyphenolic aldehyde, and it has attracted increasing attention as a possible antibacterial drug. In this paper, we studied the antimicrobial properties (minimum inhibitory concentrations) of gossypol acetate against both Gram-positive and Gram-negative bacteria strains and dig up targets of gossypol acetate using in vitro assays, including studying its effects on functions (GTPase activity and polymerization) of Filamenting temperature sensitive mutant Z (FtsZ) and its interactions with FtsZ using isothermal titration calorimetry (ITC), and in vivo assays, including visualization of cell morphologies and proteins localizations using a microscope. Lastly, Bacterial membrane permeability changes were studied, and the cytotoxicity of gossypol acetate was determined. We also estimated the interactions of gossypol acetate with the promising target. We found that gossypol acetate can inhibit the growth of Gram-positive bacteria such as the model organism Bacillus subtilis and the pathogen Staphylococcus aureus [both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA)]. In addition, gossypol acetate can also inhibit the growth of Gram-negative bacteria when the outer membrane is permeabilized by Polymyxin B nonapeptide (PMBN). Using a cell biological approach, we show that gossypol acetate affects cell division in bacteria by interfering with the assembly of the cell division FtsZ ring. Biochemical analysis shows that the GTPase activity of FtsZ was inhibited and polymerization of FtsZ was enhanced in vitro, consistent with the block to cell division in the bacteria tested. The binding mode of gossypol acetate in FtsZ was modeled using molecular docking and provides an understanding of the compound mode of action. The results point to gossypol (S2303) as a promising antimicrobial compound that inhibits cell division by affecting FtsZ polymerization and has potential to be developed into an effective antimicrobial drug by chemical modification to minimize its cytotoxic effects in eukaryotic cells that were identified in this work.

Rationally designed antifungal protein chimeras reveal new insights into structure-activity relationship

Antifungal proteins (AFPs) are promising antimicrobial compounds that represent a feasible alternative to fungicides. Penicillium expansum encodes three phylogenetically distinct AFPs (PeAfpA, PeAfpB and PeAfpC) which show different antifungal profiles and fruit protection effects. To gain knowledge about the structural determinants governing their activity, we solved the crystal structure of PeAfpB and rationally designed five PeAfpA::PeAfpB chimeras (chPeAFPV1-V5). Chimeras showed significant differences in their antifungal activity. chPeAFPV1 and chPeAFPV2 improved the parental PeAfpB potency, and it was very similar to that of PeAfpA. chPeAFPV4 and chPeAFPV5 showed an intermediate profile of activity compared to the parental proteins while chPeAFPV3 was inactive towards most of the fungi tested. Structural analysis of the chimeras evidenced an identical scaffold to PeAfpB, suggesting that the differences in activity are due to the contributions of specific residues and not to induced conformational changes or structural rearrangements. Results suggest that mannoproteins determine protein interaction with the cell wall and its antifungal activity while there is not a direct correlation between binding to membrane phospholipids and activity. This work provides new insights about the relevance of sequence motifs and the feasibility of modifying protein specificity, opening the door to the rational design of chimeras with biotechnological applicability.

Attractive study of the antimicrobial, antiviral, and cytotoxic activity of novel synthesized silver chromite nanocomposites

Antibiotic resistance is a global problem. This is the reason why scientists search for alternative treatments. In this regard, seven novel silver chromite nanocomposites were synthesized and assayed to evaluate their antimicrobial, antiviral, and cytotoxic activity. Five bacterial species were used in this study: three Gram-positive (Bacillus subtilis, Micrococcus luteus, and Staphylococcus aureus) and two Gram-negative (Escherichia coli and Salmonella enterica). Three fungal species were also tested: Candida albicans, Aspergillus niger, and A. flavus. The MIC of the tested compounds was determined using the bifold serial dilution method. The tested compounds showed good antibacterial activity. Maximum antibacterial activity was attained in the case of 15 N [Cobalt Ferrite (0.3 CoFe2O4) + Silver chromite (0.7 Ag0.5Cr2.5O4)] against M. luteus. Concerning antifungal activity, C. albicans was the most susceptible fungal species. The maximum inhibition was recorded also in case of 15 N [Cobalt Ferrite (0.3 CoFe2O4) + Silver chromite (0.7 Ag0.5Cr2.5O4)]. The most promising antimicrobial compound 15 N [Cobalt Ferrite (0.3 CoFe2O4) + Silver chromite (0.7 Ag0.5Cr2.5O4)] was assayed for its antiviral and cytotoxic activity. The tested compound showed weak antiviral activity. The cytotoxic activity against Mammalian cells from African Green Monkey Kidney (Vero) cells was detected. The inhibitory effect against Hepatocellular carcinoma cells was detected using a MTT assay. The antimicrobial effect of the tested compounds depends on the tested microbial species. The tested compounds could be attractive and alternative antibacterial compounds that open a new path in chemotherapy.

Synthesis, In Silico Prediction and In Vitro Evaluation of Antimicrobial Activity, DFT Calculation and Theoretical Investigation of Novel Xanthines and Uracil Containing Imidazolone Derivatives.

Novel xanthine and imidazolone derivatives were synthesized based on oxazolone derivatives 2a-c as a key intermediate. The corresponding xanthine 3-5 and imidazolone derivatives 6-13 were obtained via reaction of oxazolone derivative 2a-c with 5,6-diaminouracils 1a-e under various conditions. Xanthine compounds 3-5 were obtained by cyclocondensation of 5,6-diaminouracils 1a-c with different oxazolones in glacial acetic acid. Moreover, 5,6-diaminouracils 1a-e were reacted with oxazolones 2a-c in presence of drops of acetic acid under fused condition yielding the imidazolone derivatives 6-13. Furthermore, Schiff base of compounds 14-16 were obtained by condensing 5,6-diaminouracils 1a,b,e with 4-dimethylaminobenzaldehyde in acetic acid. The structural identity of the resulting compounds was resolved by IR, 1H-, 13C-NMR and Mass spectral analyses. The novel synthesized compounds were screened for their antifungal and antibacterial activities. Compounds 3, 6, 13 and 16 displayed the highest activity against Escherichia coli as revealed from the IC50 values (1.8–1.9 µg/mL). The compound 16 displayed a significant antifungal activity against Candia albicans (0.82 µg/mL), Aspergillus flavus (1.2 µg/mL) comparing to authentic antibiotics. From the TEM microgram, the compounds 3, 12, 13 and 16 exhibited a strong deformation to the cellular entities, by interfering with the cell membrane components, causing cytosol leakage, cellular shrinkage and irregularity to the cell shape. In addition, docking study for the most promising antimicrobial tested compounds depicted high binding affinity against acyl carrier protein domain from a fungal type I polyketide synthase (ACP), and Baumannii penicillin- binding protein (PBP). Moreover, compound 12 showed high drug- likeness, and excellent pharmacokinetics, which needs to be in focus for further antimicrobial drug development. The most promising antimicrobial compounds underwent theoretical investigation using DFT calculation.

In vitro antibacterial activity and potential applications in food of sea urchin (Diadema setosum) from Cape of Palette, South Sulawesi

Marine invertebrates in support of his life's defence of sea predatory use an innate immune mechanism, namely the cellular component hemocytes by secreting the dissolved antimicrobial and cytotoxic substances. It shows that marine invertebrates are potential sources and promising antimicrobial compounds. This research was aimed at determining the antibacterial activity of sea urchin (Diadema setosum) extract against some bacterial isolates and its application to foodstuffs. The gonad and shell of sea urchin extracted by methanol and ethyl acetate and then separated by ultrasound-assisted extraction. Screening of antibacterial compound use gas chromatography-mass spectrometry (GC-MS), and disc diffusion method was followed to determine the antimicrobial activity against Salmonella, Escherichia coli and Staphylococcus aureus. The results of this study showed antibacterial activity against one or more strains. The gonad of sea urchin from methanol extract exhibited significant inhibitory effect and effective against Salmonella, E. coli and S. aureus. Majority of gonad and shell of sea urchin extract showed antibacterial activity against the tested strains. However, gonad of methanol extract was found to be inhibiting microorganisms gram-negative (E. coli) and gram-positive (Salmonella and S. aureus). Gonad extract can be a good source of antibacterial agents.

Chemical composition, antioxidant, antimicrobial and anti-inflammatory activity of Prunus spinosa L. fruit ethanol extract

Abstract Prunus spinosa L. (from Italy) fruit ethanol extract (40 µg/mL) was assessed by evaluating the antioxidant, anti-inflammatory and antimicrobial activities against five bacterial and two fungi ATCC strains. Moreover, the phenolic profile was also investigated and results are indicative of an intense anthocyanin accumulation which may be responsible for the antioxidant properties revealed by the DPPH assay. MIC and MBC/MFC values (4.36–8.72 mg/mL; 8.72–17.44 mg/mL, respectively) revealed a wide antibacterial activity and yeast inhibition. No specific inhibitory action was observed against the tested Gram-negative or Gram-positive bacteria. Preliminary data on the effect on both miR-126 and miR-146a expression levels suggested a very interesting anti-inflammatory activity of the extract. A possible mechanism underpinning the observed effects was hypothesized and discussed. Finally, P. spinosa fruit extract could be used as supplementary source of functional additives and might be a promising antimicrobial compound of natural origin to be employed to fight microbial resistance.

Combined Action of Piperitenone Epoxide and Antibiotics Against Clinical Isolates of Staphylococcus aureus and Escherichia coli.

The aim of this study was to determine the antimicrobial efficiency of piperitenone epoxide (PEO) – a principal component of various aromatic plants’ essential oil – in combination with various antibiotics against 28 strains of Staphylococcus aureus and 10 strains of Escherichia coli isolated from clinical samples. Mentha spicata’s essential oil, initially collected by hydrodistillation, was then subjected to flush column chromatography affording PEO of high purity. Minimum inhibitory concentrations of PEO alone and in combination with various concentrations of antibiotics were assessed using the microdilution method. The combined action was estimated calculating the fractional inhibitory concentration (FIC) index from checkerboard assays. Our results showed that the average minimum inhibitory concentration (mg/l) of PEO alone against E. coli was 512 ± 364.7 μg/ml, which was significantly higher than 172.8 ± 180.7 μg/ml observed for S. aureus. From checkerboard assays, FIC values below the 0.5 index, indicating synergy, were observed for 59% of the drugs tested. Twelve percent of FIC index values were between 0.5 and 1, indicating additive effects, while 21% were indifferent. According to our results, PEO could be a promising antimicrobial compound when combined with specific antibiotics and deserves further study.

A novel Zn chelate (TSOL) that moves systemically in citrus plants inhibits growth and biofilm formation of bacterial pathogens.

Ternary solution (TSOL) is a novel Zn chelate-based systemic antimicrobial formulation designed for treating citrus bacterial pathogens ‘Candidatus Liberibacter asiaticus’ and Xanthomonas citri subsp. citri. TSOL is a component of MS3T, a novel multifunctional surface/sub-surface/systemic therapeutic formulation. Antimicrobial activity of TSOL was compared with the antimicrobial compound ZnO against X. citri subsp. citri and ‘Ca. L. asiaticus’ surrogate Liberibacter crescens in batch cultures. X. citri subsp. citri and L. crescens were also introduced into microfluidic chambers, and the inhibitory action of TSOL against biofilm formation was evaluated. The minimum inhibitory concentration of TSOL for both X. citri subsp. citri and L. crescens was 40ppm. TSOL was bactericidal to X. citri subsp. citri and L. crescens above 150 ppm and 200 ppm, respectively. On the contrary, ZnO was more effective as a bactericidal agent against L. crescens than X. citri subsp. citri. TSOL was more effective in controlling growth and biofilm formation of X. citri subsp. citri in batch cultures compared to ZnO. Time-lapse video imaging microscopy showed that biofilm formation of X. citri subsp. citri was inhibited in microfluidic chambers treated with 60 ppm TSOL. TSOL also inhibited further growth of already formed X. citri subsp. citri and L. crescens biofilms in microfluidic chambers. Leaf spraying of TSOL showed higher plant uptake and systemic movement in citrus (Citrus reshni) plants compared to that of ZnO, suggesting that TSOL is a promising antimicrobial compound to control vascular plant pathogens such as ‘Ca. L. asiaticus’.

Antifungal activity of solvent extracts of Piper betle and Ocimum sanctum Linn on Candida albicans: An in vitro comparative study.

Background:Oral candidiasis is a common fungal infection caused by Candida albicans. In recent years, Candida species have shown resistance against many synthetic drugs, which has highlighted the need for novel antifungal drugs with fewer side effects for effective management of candidiasis. Several studies have suggested that some plant species possess promising antimicrobial compounds. Piper betle and Ocimum sanctum Linn are such common medicinal plants that show strong antimicrobial activity by the release of secondary metabolites. However, the effect of these plants on oral candidiasis has not been studied and hence, the present study aimed to evaluate the antifungal activity of these plant extracts on the subcultures of C. albicans and compared with a standard drug, fluconazole.Materials and Methods:Subcultures of C. albicans obtained from oral thrush patients were used in the present study. Ethanolic and ethyl acetate extracts of P. betle (betel) and O. sanctum L. (tulsi) leaves were prepared by cold extraction method. The anticandidal activity and minimum inhibitory concentration (MIC) were evaluated using disc diffusion method and microbroth dilution method, respectively. Values were compared with the standard drug fluconazole.Results:Both the extracts exhibited anticandidal activity on the subcultures of C. albicans. The ethyl acetate extract of mature betel leaf showed a maximum zone of inhibition (26 mm) when compared with tulsi and fluconazole (13 mm). Betel leaf extract showed better MIC values (125 μg/ml) than tulsi (2000 μg/ml). However, these values were high when compared with those of fluconazole (62.5 μg/ml).Conclusion:Ethyl acetate extract of mature betel leaf exhibited good anticandidal activity than that of tulsi and fluconazole.

Physicochemical and In Vitro Evaluation of Drug Delivery of an Antibacterial Synthetic Benzophenone in Biodegradable PLGA Nanoparticles.

Due to the increasing incidents of antimicrobial-resistant pathogens, the development of new antibiotics and their efficient formulation for suitable administration is crucial. Currently, one group of promising antimicrobial compounds are the benzophenone tetra-amides which show good activity even against gram-positive, drug-resistant pathogens. These compounds suffer from poor water solubility and bioavailability. It is therefore important to develop dosage forms which can address this disadvantage while also maintaining efficacy and potentially generating long-term exposures to minimize frequent dosing. Biodegradable nanoparticles provide one solution, and we describe here the encapsulation of the experimental benzophenone-based antibiotic, SV7. Poly-lactic-co-glycolic-acid (PLGA) nanoparticles were optimized for their physicochemical properties, their encapsulation efficiency, sustained drug release as well as antimicrobial activity. The optimized formulation contained particles smaller than 200nm with a slightly negative zeta potential which released 39% of their drug load over 30days. This formulation maintains the antibacterial activity of SV7 while minimizing the impact on mammalian cells.

Evaluation of antimicrobial activities of microalgae Scenedesmus dimorphus extracts against bacterial strains

The study was conducted to analyze the existence of bioactive phytochemicals extracts in green alga Scenedesmus dimorphus and their antimicrobial role. Various solvents such as methanol, ethanol, N-hegzane and diethylether were used for extraction. The extracts of of Scenedesmus dimorphus were tested against two Gram - positive bacteria (Bacillus subtilis and Micrococcus luteus), a Gram - negative bacterium (A. hydrophila) and Escherichia coli by the agar well diffusion method. Four different methanolic, ethanolic, hexane and diethylether extracts showed effective inhibition against different bacterial pathogens. Diethylether extract was very effective against bacterial strains compared to other extracts. Methanolic extract effectively inhibited A. hydrophila in comparison with other extracts, while ethanolic extract did not have any inhibitory effect on the bacterium. Methanolic, ethanolic, hexane and diethylether extracts were analyzed by GC mass. The most abundant compounds in methanolic extract of S. dimorphus included esters, plasticizer compound and terpens, while in the ethanolic, N-hexane and diethylether extracts, the most abundant compounds were found to be plasticizers, hydrocarbon and esters. These results indicate the presence of promising antimicrobial compounds in the examined algal species. Further phytochemical studies are required to elucidate the structutre and detailed activities of these compounds. So, we achieved antimicrobial activity in the methanolic, ethanolic, hexane and ether extracts of green microalgae against some pathogenic bacteria as well as employing GC mass autogram for S. dimorphus extracts for preliminary detection of active constituents.

Isolation and characterization from solar salterns of North Algeria of a haloarchaeon producing a new halocin.

Halophilic archaea, thriving in hypersaline environments, synthesize antimicrobial substances with an unknown role, called halocins. It has been suggested that halocin production gives transient competitive advantages to the producer strains and represents one of the environmental factors influencing the microbial community composition. Herein, we report on the antibacterial activity of a new haloarchaeon selected from solar salterns of the northern coast of Algeria. A total of 81 halophilic strains, isolated from the microbial consortia, were screened for the production of antimicrobial compounds by interspecies competition test and against a collection of commercial haloarchaea. On the basis of the partial 16S rRNA sequencing, the most efficient halocin producer was recognized as belonging to Haloferax (Hfx) sp., while the best indicator microorganism, showing high sensitivity toward halocin, was related to Haloarcula genus. The main morphological, physiological and biochemical properties of Hfx were investigated and a partial purification of the produced halocin was allowed to identify it as a surface membrane protein with a molecular mass between 30 and 40kDa. Therefore, in this study, we isolated a new strain belonging to Haloferax genus and producing a promising antimicrobial compound useful for applications in health and food industries.