Preventative treatment with Fluorothiazinon suppressed Acinetobacter baumannii-associated septicemia in mice.

The high prevalence of multidrug-resistant Acinetobacter baumannii has emerged as a serious problem in the treatment of nosocomial infections in the past three decades. Recently, we developed a new small-molecule inhibitor belonging to a class of 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones, Fluorothiazinon (FT, previously called CL-55). FT effectively suppressed the T3SS of Chlamydia spp., Pseudomonas aeruginosa, and Salmonella sp. without affecting bacterial growth in vitro. In this study, we describe that prophylactic use of FT for 4 days prior to challenge with resistant clinical isolates of A. baumannii (ABT-897-17 and 52TS19) suppressed septic infection in mice, resulting in improved survival, limited bacteraemia and decreased bacterial load in the organs of the mice. We show that FT had an inhibitory effect on A. baumannii biofilm formation in vitro and, to a greater extent, on biofilm maturation. In addition, FT inhibited Acinetobacter isolate-induced death of HeLa cells, which morphologically manifested as apoptosis. The mechanism of FT action on A. baumannii is currently being studied. FT may be a promising candidate for the development of a broad-spectrum anti-virulence drug to use in the prevention of nosocomial infections.

Hygromycin A derivatives isolated from Streptomyces sp. PC-22 in the rhizosphere soil of Pulsatilla chinensis.

On the basis of the one strain-many compounds (OSMAC) strategy, two new hygromycin A derivatives (3, 4), together with six known compounds were isolated from a medicinal plant inter rhizospheric Streptomyces in Pulsatilla chinensis. The structures of 3 and 4 were elucidated using NMR and HRESIMS analyses. A plausible biosynthetic pathway for these compounds was discussed. All the compounds were evaluated for their antimicrobial and cytotoxic activities. Compound 5 exhibited potent inhibitory activity against S. aureus and B. subtilis with the MICs of 16 and 8 µg ml-1, while 4 showed weak inhibitory activity against S. aureus.

Biofabrication of ZnO nanoparticles using Acacia arabica leaf extract and their antibiofilm and antioxidant potential against foodborne pathogens.

Emergence of multidrug resistant pathogens is increasing globally at an alarming rate with a need to discover novel and effective methods to cope infections due to these pathogens. Green nanoparticles have gained attention to be used as efficient therapeutic agents because of their safety and reliability. In the present study, we prepared zinc oxide nanoparticles (ZnO NPs) from aqueous leaf extract of Acacia arabica. The nanoparticles produced were characterized through UV-Visible spectroscopy, scanning electron microscopy, and X-ray diffraction. In vitro antibacterial susceptibility testing against foodborne pathogens was done by agar well diffusion, growth kinetics and broth microdilution assays. Effect of ZnO NPs on biofilm formation (both qualitatively and quantitatively) and exopolysaccharide (EPS) production was also determined. Antioxidant potential of green synthesized nanoparticles was detected by DPPH radical scavenging assay. The cytotoxicity studies of nanoparticles were also performed against HeLa cell lines. The results revealed that diameter of zones of inhibition against foodborne pathogens was found to be 16-30 nm, whereas the values of MIC and MBC ranged between 31.25-62.5 µg/ml. Growth kinetics revealed nanoparticles bactericidal potential after 3 hours incubation at 2 × MIC for E. coli while for S. aureus and S. enterica reached after 2 hours of incubation at 2 × MIC, 4 × MIC, and 8 × MIC. 32.5-71.0% inhibition was observed for biofilm formation. Almost 50.6-65.1% (wet weight) and 44.6-57.8% (dry weight) of EPS production was decreased after treatment with sub-inhibitory concentrations of nanoparticles. Radical scavenging potential of nanoparticles increased in a dose dependent manner and value ranged from 19.25 to 73.15%. Whereas cytotoxicity studies revealed non-toxic nature of nanoparticles at the concentrations tested. The present study suggests that green synthesized ZnO NPs can substitute chemical drugs against antibiotic resistant foodborne pathogens.

Methanol extract from the seeds of Persea americana displays antibacterial and wound healing activities in rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: Persea americana Miller (Lauraceae) known as "pear" in Cameroon is comestible by the fruit. The leaves of the plant are traditionally used in the treatment of microbial infections, malaria, diabetes, high blood pressure, to stimulate uterine contractions and relief painful menstruations. The leaves and stem bark are also used to cure malaria and typhoid fever. Fresh pulps are used to lower cholesterol, prevents mental strain and cardiovascular diseases whilst the seeds are used against intestinal worms and skin infections. AIM OF THE STUDY: This study aimed to investigate the antibacterial activity and wound healing efficacy of methanol extract of Persea americana seed on an excision wound infected with Staphylococcus aureus using a rat model and characterise the mode of action of this extract. MATERIALS AND METHODS: The antibacterial activities of the methanol extract were done against a panel of bacteria using broth microdilution method. The phytochemical analysis as well as the antioxidant activities were evaluated using colorimetric methods. The mode of action of P. americana was studied by targeting bacterial membranes, cytoplasmic contents, and the formation of biofilms. The therapeutic effect of the methanol extract was evaluated on an excision wound infected with Staphylococcus aureus. RESULTS: The methanol extract of P. americana seed displayed antibacterial properties MIC varying from 64 to 128 µg/mL which can be linked to its total phenolic, flavonoid and tannin contents. The antibacterial activity of the extract is due to the bacterial biofilm inhibition and the perturbation of the bacterial membrane through the leakage of intracellular materials, the inhibition of H+-ATPases pumps. The gel based on P. americana extract showed a significant increase in the percentage of wound closure and had a significant reduction of the number of Colony Forming Units (CFU) of S. aureus at the infection site. The plant has antioxidant activity for wound healing which is lower than vitamin C. The toxicological report showed that the gel-based extract had negligible irritation on the skin and non-irritating to the eye, and therefore can be consider safe for use. CONCLUSION: The present study revealed the antibacterial and wound healing properties of the MEPa and could possibly be used to tackle bacterial infections.

Efficacy and Safety of Antofloxacin-Based Triple Therapy for Helicobacter pylori Eradication Failure in China.

AIMS: Quinolone-containing triple therapy has been considered as the second-line therapy for eradication of Helicobacter pylori (H. pylori). At present, there are no data to show the efficacy and safety of antofloxacin-based rescue therapy for the eradication of H. pylori, and this pilot clinical trial was designed. METHODS: A total of 196 patients who failed H. pylori eradication using the clarithromycin-based or metronidazole-based triple or bismuth quadruple therapy were randomly allocated to one of the following rescue eradication therapy groups: AEA group (antofloxacin 200 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days, or LEA group (levofloxacin 500 mg once daily, esomeprazole 20 mg + amoxicillin 1000 mg twice daily) for 14 days. The minimal inhibitory concentrations were tested by the E-test method. The gyrA mutation was analyzed by sequencing. Follow-up 13/14C-urea breath test was examined at 1 month after discontinuation. RESULTS: A total of 178 eligible patients were included in this study. The eradication rate was significantly higher in AEA group than in LEA group according to both ITT (87.6% vs. 68.5%; P = 0.002) and PP analyses (90.7% vs. 70.1%; P = 0.001). ITT analyses indicated that the eradication rate was significantly higher in AEA group than in LEA group with Asn87 mutation (78.9% vs. 31.3%; P = 0.005) and levofloxacin-resistant strains (76.9% vs. 44.2%; P = 0.003). Two groups exhibited similar adverse event rates (AEA 14.6% vs. LEA 20.2%, P = 0.323). CONCLUSIONS: The findings showed that antofloxacin may be a promising candidate in rescue therapy for H. pylori eradication failure in China.

Green synthesis of bimetallic ZnO-CuO nanoparticles and their cytotoxicity properties.

In this study, a simple and green strategy was reported to prepare bimetallic nanoparticles (NPs) by the combination of zinc oxide (ZnO) and copper oxide (CuO) using Sambucus nigra L. extract. The physicochemical properties of these NPs such as crystal structure, size, and morphology were studied by X-ray diffraction (XRD), field emission gun scanning electron microscopy (FEG-SEM), and transmission electron microscopy (TEM). The results suggested that these NPs contained polygonal ZnO NPs with hexagonal phase and spherical CuO NPs with monoclinic phase. The anticancer activity of the prepared bimetallic NPs was evaluated against lung and human melanoma cell lines based on MTT assay. As a result, the bimetallic ZnO/CuO NPs exhibited high toxicity on melanoma cancer cells while their toxicity on lung cancer cells was low.

Antibacterial and antioxidant activities of endophytic fungi and nettle (Urtica dioica L.) leaves as their host.

Nettle (Urtica dioica L), as a plant rich in biologically active compounds, is one of the most important plants used in herbal medicine. Studies have shown that this plant has antioxidant, antiplatelet, hypoglycemic and hypocholesterolemia effects. In this study, we characterized three Alternaria endophytic fungi isolated from their host U. dioica. We hypothesized that these endophytic fungi can produce new bioactive metabolites, which may possess the bioactive property with potential application in the medical and pharmaceutical industries. The antibacterial activity was evaluated against reference and isolated strains, including Methicillin-Resistant Staphylococcus aureus. A wide range of antimicrobial activities similar to those measured in nettle leaves was detected especially for Alternaria sorghi. Furthermore, the highest antioxidant activity detected with DPPH free radical scavenging was measured for A. sorghi and nettle leaves ethyl acetate extracts. In addition, whereas catalase activity was similar in the three isolated fungi and nettle leaves, total thiol content and superoxide dismutase activity were significantly higher in leaves. A. sorghi showed the best activities compared to other isolated fungi. The characterization and further production of bioactive compounds produced by this endophyte should be investigated to fight bacteria and especially those that develop drug multi-resistance.

Systematic Evaluation of the Accelerate Pheno System for Susceptibility Testing of Gram-Negative Bacteria Isolated from Blood Cultures.

Bacteremia is a major cause of morbidity and mortality. Rapid identification of pathogens for early targeted antimicrobial therapy is crucial for detecting emergence of antibiotic resistance and improving outcomes. However, there are limited data regarding the analytical performance of a rapid identification (ID) and antimicrobial susceptibility testing (AST) method like Accelerate Pheno blood culture detection system compared with the conventional methods routinely used in microbiology laboratories. We undertook a systematic quality improvement (QI) study to compare AST results obtained with Accelerate Pheno system rapid ID/AST system with a standard reference method in a university hospital microbiology laboratory. This was a single center, retrospective (5/10/19 to 8/1/19) and prospective (8/1/19 to 1/31/20) study that evaluated all blood cultures growing Gram-negative rods (GNR). We compared AST results obtained using the reference disk diffusion (DD) susceptibility method with those obtained by the Accelerate Pheno system. We calculated the error rates and categorical agreement between the Accelerate Pheno system and DD for each organism and specific drug tested. We evaluated 355 blood cultures growing GNR, of which 284 met the inclusion criteria. We grouped all Enterobacterales (n = 263) for analysis (156 Escherichia coli, 60 Klebsiella spp., 20 Proteus mirabilis, 17 Enterobacter spp., and 10 Serratia marcescens). Twenty-one Pseudomonas aeruginosa isolates were analyzed separately. For Enterobacterales, categorical agreement (CA) was ≥90% for amikacin (AMK), aztreonam (ATM), cefepime (FEP), ceftriaxone (CRO), ertapenem (ETP), gentamicin (GEN), meropenem (MEM), and tobramycin (TOB); and very major error (VME) was <5% for ampicillin/sulbactam (SAM), GEN, MEM, TOB, CRO, and ceftazidime (CAZ). For ciprofloxacin (CIP), CA was 87% and VME was 8%. For P. aeruginosa, CA was ≥90% for AMK and TOB, and VME was ≥5% for AMK, CAZ, GEN, MEM, piperacillin-tazobactam (TZP), and TOB. Accelerate Pheno rapid ID/AST system for GNR isolated from blood culture (BCs) was reliable for some but not all agents in the panel. Based on the findings from this study, our laboratory reports Accelerate Pheno system AST results only for Enterobacterales, and we limit our reports to CRO, CAZ, TZP, CIP, ATM, and GEN. IMPORTANCE This was an 8-month retrospective and prospective study looking at the analytical performance of the Accelerate Pheno system on clinical isolates obtained from patients seen in our tertiary care hospital. Most of the published literature on the analytical performance of Accelerate Pheno System has been from clinical trials with limited data from clinical microbiology laboratories postimplementation of the system. Here we compare the AST results on 355 blood cultures growing Gram-negative bacteria in Accelerate Pheno system with the CLSI reference disk diffusion (DD) method. The findings from this study highlight the "real-world" performance of the Accelerate Pheno system for Gram-negative bacteria from blood cultures. We provide data to show the reliable susceptibility testing results of Enterobacterales for most of the commonly used antimicrobial agents and significant limitation for susceptibility testing results of Pseudomonas aeruginosa on the Accelerate Pheno system.

Biosynthesis of Copper Oxide Nanomaterials Using the Seeds of Date Fruits (Phoenix dactylifera L.) and Antibacterial Activity Evaluation.

<b>Background and Objective:</b> Green chemistry approach is a simple, eco-friendly, less toxic, cost-effective and biological method. <i>Phoenix dactylifera </i>seed extract has been used as a reducing and capping agent for the green synthesis of copper oxide nanomaterials. This approach had forewarned the interest in researching natural waste products to increase the usage of alternative therapies for infectious diseases. The present investigation determined the production of biogenic copper oxide nanomaterials using the seeds of date fruits (<i>Phoenix dactylifera </i>L.) by green approaches and an eco-friendly process. <b>Materials and Methods:</b> Extract of seeds of date fruits acted as potential and effective bio capping and reductant agents for bio-synthesis of copper oxide nanoparticles. The properties of biogenic copper oxide nanomaterials were assessed and characterized by the FT-IR, SEM, EDX, XRD and TGA analysis. <b>Results:</b> All the characterization results were confirming that produced copper oxide nanomaterials are spherical in shape with a size of 30±6 nm. Synthesized copper oxide nanomaterials are highly pure forms and resistant to high temperatures. Further, the antibacterial activity of green synthesized copper oxide nanomaterials against human bacterial pathogens was evaluated by the agar well diffusion method. The maximum zone of inhibition was obtained in <i>E. coli</i> as compared to the positive control (tetracycline). <b>Conclusion:</b> The results of the antibacterial assay indicate that biogenic copper oxide nanomaterials should be considered as an antibacterial agent for the treatment and prevention of infectious diseases.

Therapeutic Effects of Inhibitor of ompA Expression against Carbapenem-Resistant Acinetobacter baumannii Strains.

The widespread of carbapenem-resistant Acinetobacter baumannii (CRAB) is of great concern in clinical settings worldwide. It is urgent to develop new therapeutic agents against this pathogen. This study aimed to evaluate the therapeutic potentials of compound 62520, which has been previously identified as an inhibitor of the ompA promoter activity of A. baumannii, against CRAB isolates, both in vitro and in vivo. Compound 62520 was found to inhibit the ompA expression and biofilm formation in A. baumannii ATCC 17978 at sub-inhibitory concentrations in a dose-dependent manner. These inhibitory properties were also observed in clinical CRAB isolates belonging to sequence type (ST) 191. Additionally, compound 62520 exhibited a bacteriostatic activity against clinical clonal complex (CC) 208 CRAB isolates, including ST191, and ESKAPE pathogens. This bacteriostatic activity was not different between STs of CRAB isolates. Bacterial clearance was observed in mice infected with bioimaging A. baumannii strain 24 h after treatment with compound 62520. Compound 62520 was shown to significantly increase the survival rates of both immunocompetent and neutropenic mice infected with A. baumannii ATCC 17978. This compound also increased the survival rates of mice infected with clinical CRAB isolate. These results suggest that compound 62520 is a promising scaffold to develop a novel therapeutic agent against CRAB infections.

Biologically synthesized iron nanoparticles (FeNPs) from Phoenix dactylifera have anti-bacterial activities.

Nanotechnology is a vast field of science with the most vibrant and conspicuous applications. The green synthesis approach is cost-effective, eco-friendly, and produces the most stable metal-based nanoparticles without the use of toxic chemicals. This study presents the green synthesis of iron nanoparticles (FeNPs). For biosynthesis of FeNPs, Phoenix dactylifera extract was used as a reducing agent and iron sulfate heptahydrate (FeSO4·7H2O) was used as a substrate. FeNPs were characterized by different techniques including UV-Visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), and nano zeta-sizer analysis. The antimicrobial activity of FeNPs synthesized by using an aqueous extract of Phoenix dactylifera was evaluated against Escherichia coli, Bacillus subtilis, Micrococcus leutus, and Klebsiella pneumoniae. A notable color change from yellow to black confirmed the synthesis of FeNPs. The sharp peak at 450 nm UV-Visible spectroscopy confirmed the synthesis of FeNPs. FTIR showed the presence of O-H and C=C stretching due to the presence of phenol and alkene functional groups. The average size of FeNPs was 6092 d.nm. The results of antimicrobial activity showed that FeNPs exhibit different potential against different bacterial strains with a maximum 25 ± 0.360 zone of inhibition against Escherichia coli. Thus, green synthesized FeNPs could be used as potential antimicrobial agents.

Well-Orientation Strategy Biosynthesis of Cefuroxime-Silver Nanoantibiotic for Reinforced Biodentine™ and Its Dental Application against Streptococcus mutans.

Dental caries results from the bacterial pathogen Streptococcus mutans (S. mutans) and is the maximum critical reason for caries formation. Consequently, the present study aims to evaluate the antibacterial activity of a newly synthesized nanoantibiotic-Biodentine formulation. The silver nanoparticles (ROE-AgNPs) were biosynthesized from the usage of Rosmarinus officinalis L. extract (ROE) and conjugated with cefuroxime to form Cefuroxime-ROE-AgNPs. Using Biodentine™ (BIOD), five groups of dental materials were prepared, in which Group A included conventional BIOD, Group B included BIOD with ROE-AgNPs, Groups C and D included BIOD with Cefuroxime-ROE-AgNPs at concentrations of 0.5% and 1.5% cefuroxime, respectively, and Group E included BIOD with 1.5% cefuroxime. The synthesized ROE-AgNPs or Cefuroxime-ROE-AgNPs were characterized for conjugating efficiency, morphology, particle size, and in vitro release. Minimum inhibitory concentration (MIC) of the cefuroxime, ROE-AgNPs, and Cefuroxime-ROE-AgNPs were additionally evaluated against cefuroxime resistant S. mutans, which furthered antibacterial efficacy of the five groups of dental materials. The UV-Visible spectrum showed the ROE-AgNPs or Cefuroxime-ROE-AgNPs peaks and their formation displayed through transmission electron microscopy (TEM), X-ray diffraction (XRD) pattern, and Fourier transforms infrared (FTIR) analysis. The end result of Cefuroxime-ROE-AgNPs showed conjugating efficiency up to 79%. Cefuroxime-ROE-AgNPs displayed the highest antibacterial efficacy against S. mutans as compared to cefuroxime or ROE-AgNPs alone. Moreover, the MIC of ROE-AgNPs and Cefuroxime-ROE-AgNPs was detected against S. mutans to be 25 and 8.5 µg/mL, respectively. Consequently, Cefuroxime-ROE-AgNPs displayed that a decrease in the MIC reached to more than three-fold less than MIC of ROE-AgNPs on the tested strain. Moreover, Cefuroxime-ROE-AgNPs/BIOD was employed as a novel dental material that showed maximum antimicrobial activity. Groups C and D of novel materials showed inhibitory zones of 19 and 26 mm, respectively, against S. mutans and showed high antimicrobial rates of 85.78% and 91.17%, respectively. These data reinforce the utility of conjugating cefuroxime with ROE-AgNPs to retrieve its efficiency against resistant S. mutant. Moreover, the nanoantibiotic delivered an advantageous antibacterial effect to BIOD, and this may open the door for future conjugation therapy of dental materials against bacteria that cause dental caries.

Phytochemical composition and In-vitro activity of ethanolic extract of Eucalyptus globulus leaves against multidrug resistant poultry pathogens.

Aim of the present study was to determine the In-vitro antibacterial activity of ethanolic extract of E. globulus leaves against common multidrug resistant poultry pathogens. Phytochemical analysis through HPLC revealed that kaempeferol (7.315min) followed by querecetin (6.655min) and myrecetin (3.655min). Percent area of kaempeferol (6826.88%) was highest, followed by myrecetin (5516.22%) and querecetin (163.748%). Phytochemical investigation of ethanolic extract of E. globulus leaves through GCMS showed highest retention time (min) α-pinene (20.43) and α-terpineol (20.15) accompanied by spathulenol (11.97), piperitone (11.04). The ethanolic extracts of E. globulus leaves showed a highest zone of inhibition against S. pullorum SP6; 20.64± 2.08, E. coli SE 12; 19.75± 2.83, C. perfringens type A (CPM38-01); 19.46± 2.02. The highest level of MIC of E. globulus noted were against S. gallinarum S22; 133.37±53.294, S. gallinarum S1; 130.20±45.10, S. gallinarum S4; 129.47±24.182, S. gallinarum S3; 126.83±72.392. In conclusion, the study confirmed that the ethanolic extract of E. globulus is composed of active ingredients having antibacterial activity and can be referred as an alternate to antibiotics.

Evaluation of antidiabetic, antioxidant, and cytotoxic potential of maize (zea mays l.) husk leaf extracts.

In current study, Maize (Zea mays L.) husk leave extracts were appraised for biological activities such as cytotoxicity, antidiabetic, antioxidant and antimicrobial. Maceration was performed to collect various fractions of husk leave extracts using a pool of solvents i.e., n-hexane, chloroform, ethyl acetate, butanol and methanol. Antioxidant potential was measured by 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging, reducing power and linoleic acid oxidation assay, using butylated hydroxy toluene (BHT) as a positive control. Total phenolic and flavonoid contents were found to be 18.47-425.11 mg/100 g GAE and 5.83-16.72 mg/100 g CE, respectively. The DPPH scavenging assay was exhibited in the range of 76.36 to 88.53%. The percentage inhibition in linoleic acid oxidation was found from 10.16 to 79.51%. Significant antimicrobial activity was demonstrated by husk leaf extracts against bacterial strains and fungal strains using disc diffusion and minimum inhibitory concentration (MIC) method. Amylase alpha assay was employed to analyze the antidiabetic activity which ranged between 9.52-24.81%. Cytotoxicity was evaluated by % age lysis (0.35-9.54%), while thrombolytic activity ranged between 7.67 to 31.27%. The results presented in this study revealed that maize (Zea mays L.) husk leaf extracts can be a valuable source of biologically active compounds and may be consumed as a source of potent herbal medicine in pharmaceuticals.

UPLC-QTOF-MS/MS analysis and antibacterial activity of the Manilkara zapota (L.) P. Royen against Escherichia coli and other MDR bacteria.

With the spread of bacterial resistance against clinically used antibiotics, natural plant-derived products are being studied as new sources of antibacterial molecules. Manilkara zapota is a common plant species in the American continent that is used as a food source. Studies show the M. zapota extract is rich in phenolic substances that can serve as basic molecules for the pharmaceutical industry. An extract from fresh M. zapota leaves was produced and tested to identify the compounds present, as well as its direct antibacterial and clinical antibiotic modulatory activities. To analyze the results, a new statistical methodology based on the Shannon-Wiener index was tested, capable of correcting distortions in heterogeneous environments. The Hydroethanolic Extract of Manilkara zapota leaves (HEMzL) presented a wide variety of phenolic products, as well as tannins, in the UPLC analysis. The extract showed direct antibacterial activity against the standard Staphylococcus aureus strain, however, it either acted antagonistically when associated with the tested antibiotics, or it did not present statistical significance when compared to the control. This demonstrates a need to be cautious when associating natural products with antibiotics for clinical use, as a hindrance to infectious treatments may occur. As for the statistical analysis mechanism tested, this proved to be effective, reducing false negatives at low antibiotic concentrations and false positives at high concentrations in the microdilution plate.

Antimicrobial and antibiofilm potential of Curcuma longa Linn. Rhizome extract against biofilm producing Staphylococcus aureus and Pseudomonas aeruginosa isolates.

More than 65% of all human bacterial infection are associated with biofilm. Bacteria in such biofilms are 10 to 1000-fold more resistant to antibiotics than free living bacteria cells. Organisms such as S. aureus and P. aeruginosa are responsible for a significant number of biofilm related infections. In this study, we investigated the antimicrobial and anti-biofilm activity of C. longa L. rhizome extract against biofilm producing S. aureus and P. aeruginosa isolates. The results of MIC and MBC demonstrated promising antibacterial activity of the rhizome extract. TLC and column chromatography detected various curcuminoids while phytochemical analysis also reveals presence of number of bioactive compounds such as alkaloids, flavonoids, phenolics, terpenoids, etc. Micro titer plate assay indicated significant inhibition of biofilm formation in clinical isolates treated with turmeric extract. Thus, on basis of our results turmeric extracts can be considered as natural antibiofilm and antibacterial agent.

Antibacterial, Antibiofilm, and Efflux Pump Inhibitory Properties of the Crude Extract and Fractions from Acacia macrostachya Stem Bark.

Microbial infections remain a public health problem due to the upsurge of bacterial resistance. In this study, the antibacterial, antibiofilm, and efflux pump inhibitory activities of the stem bark of Acacia macrostachya, an indigenous African medicinal plant, were investigated. In traditional medicine, the plant is used in the treatment of microbial infections and inflammatory conditions. A crude methanol extract obtained by Soxhlet extraction was partitioned by column chromatography to obtain the petroleum ether, ethyl acetate, and methanol fractions. Antibacterial, efflux pump inhibition and antibiofilm formation activities were assessed by the high-throughput spot culture growth inhibition (HT-SPOTi), ethidium bromide accumulation, and the crystal violet retention assay, respectively. The minimum inhibitory concentrations (MICs) of the crude extract and major fractions ranged from 250 to ≥500 µg/mL. At a concentration of 3.9-250 µg/mL, all extracts demonstrated >80% inhibition of biofilm formation in S. aureus. In P. aeruginosa, the EtOAc fraction showed the highest antibiofilm activity (59-69%) while the pet-ether fraction was most active against E. coli biofilms (45-67%). Among the test samples, the crude extract, methanol, and ethyl acetate fractions showed remarkable efflux pump inhibition in S. aureus, E. coli, and P. aeruginosa. At ½ MIC, the methanol fraction demonstrated significant accumulation of EtBr in E. coli having superior efflux inhibition over the standard EPIs: chlorpromazine and verapamil. Tannins, flavonoids, triterpenoids, phytosterols, coumarins, and saponins were identified in preliminary phytochemical studies. Stigmasterol was identified in the EtOAc fraction. This study justifies the use of A. macrostachya in the treatment of infections in traditional medicine and highlights its potential as a source of bioactive compounds that could possibly interact with some resistance mechanisms in bacteria to combat antimicrobial resistance.

Antifungal Evaluation and Molecular Docking Studies of Olea europaea Leaf Extract, Thymus vulgaris and Boswellia carteri Essential Oil as Prospective Fungal Inhibitor Candidates.

Background: The present study investigated the antifungal activity and mode of action of four Olea europaea leaf extracts, Thymus vulgaris essential oil (EO), and Boswellia carteri EO against Fusarium oxysporum. Methods:Fusarium oxysporum Lactucae was detected with the internal transcribed spacer (ITS) region. The chemical compositions of chloroform and dichloromethane extracts of O. europaea leaves and T. vulgaris EO were analyzed using GC-MS analysis. In addition, a molecular docking analysis was used to identify the expected ligands of these extracts against eleven F. oxysporum proteins. Results: The nucleotide sequence of the F. oxysporum Lactucae isolate was deposited in GenBank with Accession No. MT249304.1. The T. vulgaris EO, chloroform, dichloromethane and ethanol efficiently inhibited the growth at concentrations of 75.5 and 37.75 mg/mL, whereas ethyl acetate, and B. carteri EO did not exhibit antifungal activity. The GC-MS analysis revealed that the major and most vital compounds of the T. vulgaris EO, chloroform, and dichloromethane were thymol, carvacrol, tetratriacontane, and palmitic acid. Moreover, molecular modeling revealed the activity of these compounds against F. oxysporum. Conclusions: Chloroform, dichloromethane and ethanol, olive leaf extract, and T. vulgaris EO showed a strong effect against F. oxysporum. Consequently, this represents an appropriate natural source of biological compounds for use in healthcare. In addition, homology modeling and docking analysis are the best analyses for clarifying the mechanisms of antifungal activity.

Effectiveness of tenofovir alafenamide for chronic hepatitis B patients with a poor response to the previously used nucleos(t)ide analogs.

BACKGROUND: Few studies have demonstrated the potency of tenofovir alafenamide (TAF) in patients with poor response to other nucleos(t)ide analogs (NAs). METHODS: We conducted a retrospective study comprising consecutive 40 patients exhibiting a poor response to other NAs, who subsequently received TAF-containing regimens. The primary outcome was the prevalence of virological response (VR) at each time and maintained virological response (MVR) under TAF-containing regimens until week 96. RESULTS: In the entire cohort, the prevalence of MVR was 71.1% (27/38). Further, poor tenofovir disoproxil fumarate (TDF) response was significantly associated with a lower prevalence of MVR (p = 0.014). In TDF-naïve patients, the prevalence of MVR was 92.3% (12/13) and 62.5% (5/8) in patients with lamivudine resistance (LAM-r) and entecavir resistance (ETV-r), respectively. Further, viral load and HBeAg status at baseline were associated with a lower prevalence of MVR (p = 0.013). Among the seven patients with prior TDF exposure, 2 patients achieved MVR. Among them, one patient with development of viral breakthrough during TDF/LAM achieved MVR after switching to TAF/ETV. In contrast, one of the five patients with non-MVR had three substitutions (rtS106C, rtD134N/S, and rtL269I) of quadruple mutations in addition to ETV-r. Other patients with rtA181T + rtN236T also could not achieve MVR. CONCLUSION: TAF exhibited high antiviral potency in patients with LAM-r and ETV-r. However, TAF potency was associated with previous TDF response, viral load, and HBeAg status at baseline. Additionally, a quadruple mutation may impact tenofovir resistance; however, further studies are needed to verify this.

Isolation, Docking and In Silico ADME-T Studies of Acacianol: Novel Antibacterial Isoflavone Analogue Isolated from Acacia leucophloea Bark.

BACKGROUND: The plant Acacia leucophloea (Roxb.) Willd. of the family Fabaceae is of paramount importance in Indian medicine. OBJECTIVES: We sought to evaluate the in vitro anti-microbial activity of A. leucophloea stem bark extract together with its phytochemical characterization and exploration of drug-likeness attributes. METHODS: In vitro Kirby-Bauer disc-diffusion and tube-dilution assays were exploited for determining the anti-microbial activity of the methanolic bark extracts against several bacterial test strains. Spectral characterization of the isolated phytoconstituents was performed using spectroscopy techniques viz., UV, IR, 1H NMR, and mass spectroscopy followed by the in silico studies like docking and ADME-T studies. RESULTS: The crude methanolic extracts were active against all the bacterial test strains, albeit weakly or moderately, as indicated by the zone of inhibition and minimum inhibitory concentration in the anti-microbial assays. The isolated phytoconstituent was identified to be 3-(3,4-dihydro-5-methoxy-2H-chromen-6-yl)-2,5- dimethoxy-2H-chromen-7-ol (hereby coined as acacianol), a novel isoflavone analog. Acacianol demonstrated a strong binding affinity towards the bacterial DNA gyrase over clorobiocin, especially in the case of cavity 4 with no predicted toxicities in silico, except skin sensitization and chromosome damage.