Spectrum Of Antibacterial Activity Research Articles

Isolation and purification of antibacterial lipopeptides from Bacillus velezensis YA215 isolated from sea mangroves.

The increasing burden and health risks of antimicrobial resistance (AMR) pose a great threat to society overall. Lipopeptides exhibit great potential as novel and safe alternatives to traditional antibiotics. In this study, the strain YA215, which was isolated from the mangrove area in Beibu Gulf, Guangxi, China, was identified as Bacillus velezensis. Then, YA215 lipopeptide extracts (YA215LE) from B. velezensis was found to exhibit a wide spectrum of antibacterial and antifungal activities. Additionally, YA215LE was identified and found to contain three groups of lipopeptides (surfactin, iturin, and fengycin). Furthermore, one separation fraction (BVYA1) with significant antibacterial activity was obtained. Additionally, liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis of BVYA1 showed three molecular ion peaks ([M + H]+: m/z 980.62; 994.66; 1008.66) corresponding to conventional surfactin homologs. By MS/MS analysis, BVYA1 was identified as sufactin with the precise amino acid sequence Glu-Leu/Ile-Leu-Val-Asp-Leu-Leu/Ile and hydroxyl fatty acids with 11-13 carbons. [M + H]+ at m/z 980.62 was detected for the first time in B. velezensis, which demonstrates that the strain corresponds to a new surfactin variant. In particular, BVYA1 showed antibacterial activity with the minimum inhibitory concentration (MIC) values of 7.5-15 μg/ml. Finally, the preliminary mechanism of inhibiting E. coli treated with BVYA1 showed that BVYA1 effectively permeabilized the cytoplasmic membrane and disrupted the morphology of targeted bacterial cells. In conclusion, this study suggests that the YA215LE from B. velezensis YA215 might be a potential candidate for a bactericide.

Anti-Virulence Potential of a Chionodracine-Derived Peptide against Multidrug-Resistant Pseudomonas aeruginosa Clinical Isolates from Cystic Fibrosis Patients.

Pseudomonas aeruginosa is an opportunistic pathogen causing several chronic infections resistant to currently available antibiotics. Its pathogenicity is related to the production of different virulence factors such as biofilm and protease secretion. Pseudomonas communities can persist in biofilms that protect bacterial cells from antibiotics. Hence, there is a need for innovative approaches that are able to counteract these virulence factors, which play a pivotal role, especially in chronic infections. In this context, antimicrobial peptides are emerging drugs showing a broad spectrum of antibacterial activity. Here, we tested the anti-virulence activity of a chionodracine-derived peptide (KHS-Cnd) on five P. aeruginosa clinical isolates from cystic fibrosis patients. We demonstrated that KHS-Cnd impaired biofilm development and caused biofilm disaggregation without affecting bacterial viability in nearly all of the tested strains. Ultrastructural morphological analysis showed that the effect of KHS-Cnd on biofilm could be related to a different compactness of the matrix. KHS-Cnd was also able to reduce adhesion to pulmonary cell lines and to impair the invasion of host cells by P. aeruginosa. A cytotoxic effect of KHS-Cnd was observed only at the highest tested concentration. This study highlights the potential of KHS-Cnd as an anti-biofilm and anti-virulence molecule against P. aeruginosa clinical strains.

Structural Features, Mechanisms of Action, and Prospects for Practical Application of Class II Bacteriocins.

Bacteriocins are antimicrobial peptides ribosomally synthesized by both Gram-negative and Gram-positive bacteria, as well as by archaea. Bacteriocins are usually active against phylogenetically related bacteria, providing competitive advantage to their producers in the natural bacterial environment. However, some bacteriocins are known to have a broader spectrum of antibacterial activity, including activity against multidrug-resistant bacterial strains. Multitude of bacteriocins studied to date are characterized by a wide variety of chemical structures and mechanisms of action. Existing classification systems for bacteriocins take into account structural features and biosynthetic pathways of bacteriocins, as well as the phylogenetic affiliation of their producing organisms. Heat-stable bacteriocins with molecular weight of less than 10 kDa from Gram-positive and Gram-negative producers are divided into post-translationally modified (class I) and unmodified peptides (class II). In recent years there has been an increasing interest in the class II bacteriocins as potential therapeutic agents that can help to combat antibiotic-resistant infections. Advantages of unmodified peptides are relative simplicity of their biotechnological production in heterologous systems and chemical synthesis. Potential for the combined use of bacteriocins with other antimicrobial agents allowing to enhance their efficacy, low probability of cross-resistance development, and ability of probiotic strains to produce bacteriocins in situ make them promising candidate compounds for creation of new drugs. The review focuses on structural diversity of the class II bacteriocins and their practical relevance.

Peptidomics-based identification of an antimicrobial peptide derived from goat milk fermented by Lactobacillus rhamnosus (C25).

Antimicrobial peptides (AMPs) are emerging as promising novel drug applicants. In the present study, goat milk was fermented using Lactobacillus rhamnosus C25 to generate bioactive peptides (BAPs). The peptide fractions generated were separated using ultrafiltration membranes with molecular weight cut-offs of 3, 5, and 10kDa, and their antimicrobial activity toward Gram-positive and Gram-negative bacteria was investigated. Isolated AMPs were characterized using RP-HPLC and identified by LC-MS/MS. A total of 569 sequences of peptides were identified by mass spectrometry. Out of the 569, 36 were predicted as AMPs, 21 were predicted as cationic, and out of 21, 6 AMPs were helical peptides. In silico analysis indicated that the majority of peptides were antimicrobial and cationic in nature, an important factor for peptide interaction with the negative charge membrane of bacteria. The results showed that the peptides of <5kDa exhibited maximum antibacterial activity against E. faecalis, E. coli, and S. typhi. Further, molecular docking was used to evaluate the potent MurD ligase inhibitors. On the basis of ligand binding energy, six predicted AMPs were selected and then analyzed by AutoDock tools. Among the six AMPs, peptides IGHFKLIFSLLRV (-7.5kcal/mol) and KSFCPAPVAPPPPT (-7.6kcal/mol), were predicted as a high-potent antimicrobial. Based on these findings, in silico investigations reveal that proteins of goat milk are a potential source of AMPs. This is for the first time that the antimicrobial peptides produced by Lactobacillus rhamnosus (C25) fermentation of goat milk have been identified via LC-MS/MS and predicted as AMPs, cationic charges, helical structure in nature, and potent MurD ligase inhibitors. These peptides can be synthesized and improved for use as antimicrobial agents. PRACTICAL APPLICATIONS: Goat milk is considered a high-quality source of milk protein. According to this study, goat milk protein is a potential source of AMPs, Fermentation can yield goat milk-derived peptides with a broad antibacterial activity spectrum at a low cost. The approach described here could be beneficial in that the significant AMPs can be synthesized and used in the pharmaceutical and food industries.

Isolation and identification of endophytic actinobacteria from Citrullus colocynthis (L.) Schrad and their antibacterial properties

BackgroundAntibiotic resistance poses a major threat to human health globally. Consequently, new antibiotics are desperately required to discover and develop from unexplored habitats to treat life-threatening infections. Microbial natural products (NP) are still remained as primary sources for the discovery of new antibiotics. Endophytic actinobacteria (EA) which are well-known producers of bioactive compounds could provide novel antibiotic against pathogenic bacteria. This research aimed to isolate EA from the Citrullus colocynthis plant and explore the antibacterial properties of their metabolites against pathogenic bacteria.ResultsThe healthy samples were collected, dissected and surface-sterilized before cultured on four different selection media at 28 °C. Six endophytic actinobacteria were isolated from Citrullus colocynthis plant. They were taxonomically classified into two family namely Streptomycetaceae and Nocardiopsaceae, based on colony morphological features, scanning electron microscope analysis and molecular identification of isolates. This is the first report on the identification of EA form Citrullus colocynthis and their antibacterial activity. The strains generated a chain of vibrio-comma, cubed or cylindrical shaped spores with indenting or smooth surfaces. Three of those were reported as endophytes for the first time. The strain KUMS-C1 showed 98.55% sequence similarity to its closely related strains which constitutes as a novel species/ strain for which the name Nocardiopsis colocynthis sp. was proposed for the isolated strain. Five isolated strains had antagonist activity against S. aureus, P. aeruginosa, and E. coli. Among those, stain KUMS-C6 showed the broadest spectrum of antibacterial activity against all test bacteria, whereas the strain KUMS-C4 had no antibacterial activity.ConclusionsNPs have a long history of safe and efficient use for development of pharmaceutical products. Our study highlights that Citrullus colocynthis is an untapped source for the isolation of EA, generating novel and bioactive metabolites by which might lead to discovery of new antibiotic(s). This study reveals the future of new antibiotic developments looks bright against multi-drug resistance diseases by mining under- or unexplored habitats.

Green synthesis of cobalt oxide nanoparticles using roots extract of Ziziphus Oxyphylla Edgew its characterization and antibacterial activity

In this modern era, antibiotic resistance is a significant issue that poses a threat to public health. Nanotechnology is an emerging field of science because nanoparticles could be the best alternative to antibiotics. Most nanoparticles are prepared by the green synthesis method because of their less toxicity, low cost, and non-hazardous nature. In this study, cobalt oxide nanoparticles (Co3O4-NPs) were synthesized from roots extract of Ziziphus Oxyphylla Edgew by using cobalt chloride hexahydrate. After the successful synthesis of nanoparticles, various methods were used to analyze these nanoparticles, including Fourier transform infrared spectroscopy, scanning electron microscopy, x-ray diffraction analysis, and energy dispersive analysis of x-ray. Scanning electron microscopy images reveal the spherical and irregular structure of Co3O4-NPs shaving a particle size between 40 to 60 nm. X-ray diffraction analysis revealed the crystalline nature of cobalt oxide nanoparticles with face-centered cubic structure and a size of 15–20 nm. The antibacterial activity of Co3O4-NPs was analyzed for different dilutions against two different bacteria: gram-negative (E. coli) and gram-positive (S. aureus) bacteria. The maximum zone of inhibition against gram-negative E. coli was calculated as 23.1 mm and 14.8 mm against S. aureus at a dilution of 16 mg ml−1 of cobalt oxide nanoparticle. This revealed the wide spectrum of antibacterial activity of the synthesized nanoparticle. It is suggested that root extract of cobalt oxide nanoparticles could be of great importance in pharmaceutical and medical science for their antimicrobial activity.

Isolation, characterization, bacteriocin production and biological potential of Bifidobacteria of ruminants

Bacteriocins exhibited a wide spectrum of antibacterial activity against different pathogens. The aim of current study was to characterize the bacteriocins produced by Bifidobacterium spp. isolated from ruminants. The Bifidobacterium isolates were identified as B. longum, B. pseudolongum, B. bifidum, B. thermophilum, B. boum, B. merycicum and B. ruminantium. Bacteriocins were found to be pH stable, heat resistant, highly diffusible, NaCl tolerant and resistant to UV radiations. SDS, EDTA and urea induced 14%, 21% and 24% bacteriocins activity loss. Modified MRS broth (1% tryptone, 1% yeast extract and 2% glucose) was found to be the best nutrient medium for optimal production of bacteriocins. Minimum inhibitory concentration (MIC) values varied from 300 μl/ml to 500 μl/ml and minimum bactericidal concentration (MBC) values ranged from 500 μl/ml to >500 μl/ml for E. coli and S. aureus respectively. The highest protein concentration (29.0248 mg/ml) was recorded for Bifidobacteria bacteriocin produced by B. longum. Tricine-Sodium Dodecyl Sulfate-Poly Acrylamide Gel Electrophoresis (SDS-PAGE) revealed that molecular weight of isolated bifidobacterial bacteriocins was in the range of 3.6 kDa–30 kDa. Current study indicated that bifidobacterial bacteriocins have considerable potential to be used as biopreservative.

Evaluation of Bioactive Secondary Metabolites from Ponyfish Associated Bacteria (&lt;i&gt;Photobacterium leiognathi&lt;/i&gt;)

The marine environment continues to surprise us by producing novel bioactive substances with a wide range of benefits for humans. Materials and Methods: Marine bioluminescent bacteria Photobacterium leiognathi was isolated from pony fish, Secutorruconius which was confirmed with microscopic and molecular characterization. The secondary metabolite of the isolated bacteria was extracted with dichloromethane. The chemical fingerprinting of the isolated metabolite was analyzed through TLC, FT-IR, and HPLC. The nature of the compound present in the metabolite was identified in the gas chromatography-mass spectrometry analysis (GC - MS). The isolated extract was investigated for its antibacterial property against 10 human pathogenic bacteria and also its antioxidant activity using different assays such as 1, 1-Diphenyl-2-picrylhydrazyl, Phosphomolybdenum, Metal chelating, Hydroxyl radical scavenging and hydrogen peroxide scavenging activity. Results: The Presence of functional groups including phenols, sugars, and amino acids in the extracts were identified by TLC. Totally, nine peaks were obtained for the crude extract through the FTIR spectrum range of 400 to 4000 cm-1 for the active sample. The DCM extract showed a broad spectrum of antibacterial activity against the six human bacterial pathogens. Secondary metabolites from the bioluminescent bacteria, P. leiognathi, have strong antioxidant properties. These results will be instrumental in developing novel products with biosensors and bio-imaging applications using P. leiognathi.

Broad-Spectrum Antibacterial Activity of Synthesized Carbon Nanodots from d-Glucose.

Carbon nanodots, a class of carbon nano-allotropes, have been synthesized through different routes and methods from a wide range of precursors. The selected precursor, synthetic method, and conditions can strongly alter the physicochemical properties of the resulting material and their intended applications. Herein, carbon nanodots (CNDs) have been synthesized from d-glucose by combining pyrolysis and chemical oxidation methods. The effect of the pyrolysis temperature, equivalents of oxidizing agent, and refluxing time were studied on the product and quantum yield. In the optimum conditions (pyrolysis temperature of 300 °C, 4.41 equiv of H2O2, 90 min of reflux) CNDs were obtained with 40% and 3.6% of product and quantum yields, respectively. The obtained CNDs are negatively charged (ζ-potential = -32 mV), excellently dispersed in water, with average diameter of 2.2 nm. Furthermore, ammonium hydroxide (NH4OH) was introduced as dehydrating and/or passivation agent during CNDs synthesis resulting in significant improvement of both product and quantum yields of about 1.5 and 3.76-fold, respectively. The synthesized CNDs showed a broad spectrum of antibacterial activities toward different Gram-positive and Gram-negative bacteria strains. Both synthesized CNDs caused highly colony forming unit reduction (CFU), ranging from 98% to 99.99% for most of the tested bacterial strains. However, CNDs synthesized in the absence of NH4OH, due to a negatively charged surface enriched in oxygenated groups, performed better in zone inhibition and minimum inhibitory concentration. The elevated antibacterial activity of high-oxygen-containing carbon nanodots is directly correlated to their ROS formation ability.

Glycopeptide Antibiotics: Structural and Functional Aspects, Human Medicinal Use, and Standardisation

In recent years, glycopeptide antibiotics have been widely used to treat severe bacterial infections. The long-term use of first-generation antibiotics of this group (vancomycin, teicoplanin) has contributed to the emergence of bacteria resistant to them. The problem of resistance has motivated the development of three new glycopeptide antibiotics: dalbavancin, telavancin, and oritavancin. The aim of this study was to consolidate and analyse the data from literature and current quality standards related to glycopeptide antibiotics. The article presents basic information about the discovery of glycopeptide antibiotics of natural origin (vancomycin, teicoplanin) and their derivatives (telavancin, oritavancin, dalbavancin). It briefly characterises the structures of the glycopeptide antibiotics under consideration and describes their main properties, application, and distribution in the pharmaceutical market. The article also gives information on the spectra of antibacterial activity of vancomycin, teicoplanin, and their semi-synthetic derivatives. It considers approaches to vancomycin and teicoplanin standardisation and covers the main requirements of leading pharmacopoeias for the quality of vancomycin, teicoplanin, and the corresponding medicinal products. According to the study results, glycopeptide antibiotics are still widely prescribed because of their high effectiveness in diseases caused by Gram-positive bacteria. However, at present, leading pharmacopoeias have developed and implemented quality standards only for two antibiotics of the group: vancomycin and teicoplanin. According to the results of literature consolidation, further modification of glycopeptide antibiotics is aimed at creating compounds characterised by prolonged action and greater effectiveness against pathogenic microorganisms. Thus, the attention of researchers should be directed to further standardisation of the newest derivatives of glycopeptide antibiotics: telavancin, oritavancin, and dalbavancin.

A novel antibiotic combination of linezolid and polymyxin B octapeptide PBOP against clinical Pseudomonas aeruginosa strains

BackgroundAntibiotic-resistant Gram-negative bacteria are becoming a major public health threat such as the important opportunistic pathogen Pseudomonas aeruginosa (P. aeruginosa). The present study investigated enhancement of the linezolid spectrum, which is normally used to treat Gram-positive bacteria, at inhibiting P. aeruginosa growth.MethodsThe checkerboard test or time-kill assay were carried out to determine the antibacterial effects of linezolid in cooperation with polymyxin B octapeptide PBOP (LP) against P. aeruginosa based on in vitro model. The protective effect of LP against P. aeruginosa infection was assessed based on a Caenorhabditis elegans (C. elegans) model.ResultsThe synergistic activity and antibacterial effects were significantly increased against P. aeruginosa by LP treatment, while linezolid and PBOP as monotherapies exhibited no remarkably bactericidal activity against the clinical strains. Additionally, LP treatment modified biofilm production, morphology, swimming motility of P. aeruginosa, and protected C. elegans from P. aeruginosa infection.ConclusionsThis research demonstrates that LP combination has significant synergistic activity against P. aeruginosa, and PBOP is potential to be an activity enhancer. Notably, this strategy improved the antibacterial activity spectrum of linezolid and other anti-Gram-positive agents and represents an effective choice to surmount the antibiotic resistance of bacteria in the long term.

Bioactive characterization of multifloral honeys from Apis cerana cerana, Apis dorsata, and Lepidotrigona flavibasis

Honey is a complex food product, and has been linked to a number of substantial health advantages. The aim of this study was to assess the phenolic compounds, organic acids, microbial community, antioxidant activity, and antimicrobial activity of multifloral honeys produced by Apis cerana cerana, A. dorsata, and Lepidotrigona flavibasis in Hainan province, China. Our results illustrated that chlorogenic acid was the major phenolic component in all honeys. L. flavibasis honey showed the greatest antioxidant activity (DPPH IC50 value, 7.66 mg/mL; FRAP value, 5217.06 µmol TE/kg), as well as the highest levels of proline (548.64 mg/kg), total flavonoid (11.67 mg QE/100 g), total phenolic (132.73 mg GAE/100 g), and Lactobacillus (96.28 %). Besides, all honeys were found to have a broad spectrum of antibacterial activity. Overall, our data imply that Hainan honeys, particularly stingless bee honeys, have been beneficial components of human diets.

Studying synergy of antibacterial drugs using the “checkerboard” method and the “time-kill” analysis

The use of combinations of antibiotics is a promising area of antibiotic therapy of bacterial infections caused by antibiotic-resistant strains. The main goal of combined antibiotic therapy is to achieve a synergistic effect and to expand a spectrum of antibacterial activity against multi-resistant microorganisms. Due to the presence of various mechanisms of resistance in bacteria, even to drugs of the same group, the microbiological efficacy of antibiotic combinations is difficult to predict. Therefore, to select effective combinations of antibiotics, it is required to conduct a microbiological testing of isolates isolated from a particular patient. Currently, in the Republic of Belarus, the appointment of combined antibiotic therapy is carried out empirically, and in the event of its clinical ineffectiveness, the drugs are replaced. One of the reasons for a limited testing, with the availability of culture media and diagnostic materials, is the lack of regulatory and technical methods for identifying synergy adapted to local microbiological laboratories. The purpose of this publication was to analyze the literature data illustrating the relevance of analyzing the methods for studying the effects of synergy of antibacterial drugs and the possibility of their introduction into practical medicine. As a result of a search for publications in the PubMed database on the topic of increasing the antibacterial effect of antibiotics on the request the “checkerboard” method and the “time-kill” analysis for the period from 2016 to 2021, 947 results were found with an upward trend in research. “Checkerboard” and “time-kill” assays are the most common, reliable in vitro tests that reflect the effects of antibiotic combinations and the effects of antibiotic combinations with other compounds.

Spectral characterization of the bioactive principles and antibacterial properties of cold methanolic extract of Olea europaea from the Hail region of Saudi Arabia

This work aimed to identify the bioactive constituents and antibacterial activity of a cold methanolic extract of Olea europaea leaves. GC–MS analysis of the cold methanolic extract of the leaves of O. europaea L. revealed several unique bioactive compounds, including 9,12-octadecadienoic acid (Z,Z)-, n-hexadecanoic acid, 9-octadecenamide, (Z)-, hexadecanoic acid, 2-hydroxy-1-(hydroxymethyl)ethyl ester, squalene, 2-(2-Hydroxy-2-phenylethyl)-3,5,6-trimethylpyrazine, Benzoic acid, 4-formyl-, methyl ester, 2-Methoxy-4-vinylphenol, Vitamin E etc. The FT-IR spectrum revealed distinct fingerprint regions at 3313, 2943, 2831, 1662, 1590, 1449, 1300, 1111, and 1020 cm −1 . The fingerprinting region is associated with the presence of several bioactive chemicals as determined by GC–MS analyses. The methanolic extract of O. europaea leaves revealed a broader spectrum of antibacterial activity. On the other hand, the spectrum of activity was substantially narrower than that of standard ciprofloxacin discs.

Culture Media Composition Influences the Antibacterial Effect of Silver, Cupric, and Zinc Ions against Pseudomonas aeruginosa.

Different metals, such as silver (Ag), copper (Cu), and zinc (Zn), have been broadly investigated as metals and cations used both in medicine and everyday life due to their broad spectrum of antibacterial activity. Although the antibacterial action of those metals and their ions is well known and studied, the main problem remains in the standardization of experimental procedures to determine the antimicrobial activity as bacteriological media composition might significantly influence the outcome. The presented study aimed to evaluate the appropriability of different culture media (four nutritionally rich and four minimal) in the testing of the antibacterial activity of Ag+, Cu2+, and Zn2+ ions against Pseudomonas aeruginosa. Our investigation revealed the influence of medium ingredients and the presence of phosphates, which significantly reduced the activity of tested metal ions. Moreover, the precipitate formation and decrease in pH in the minimal media were additionally observed. It was assumed that the most favorable medium for metal ion activity testing was Luria-Bertani complex medium and MOPS minimal medium.

Tetracycline-loaded magnesium oxide nanoparticles with a potential bactericidal action against multidrug-resistant bacteria: In vitro and in vivo evidence

Worldwide, the emergence of diarrhoea-causing multi-drug resistant (MDR) bacteria has become a crucial problem in everyday life. Tetracycline (TC) is a bacteriostatic agent that has a wide spectrum of antibacterial activity. One potential strategy to enhance the penetration and antibacterial activity of antibiotics is the use of nanotechnology. In this context, this study dealt with the synthesis of TC loading in biocompatible magnesium oxide nanoparticles (MgONPs), its characterization, and the potency of killing against diarrhoea-causing MDR bacteria E. coli and S. flexneri. TC loaded- MgONPs (MgONPs-TC) were characterized by DLS, SEM-EDS, UV–vis spectroscopy, and FTIR techniques with adequate physical properties. Antibacterial and antibiofilm studies indicate that this nanoparticle successfully eradicated both planktonic and sessile forms of those bacteria. It also significantly reduced the production of bacterial EPS, different levels of antioxidant enzymes, and induced reactive oxygen species (ROS) in the bacterial cell as a mode of antibacterial action. In particular, MgONPs-TC were efficient in reducing the colonization of MDR E. coli and S. flexneri in the C. elegans model. Therefore, all these data suggest that MgONPs-TC are a highly promising approach to combating diseases associated with diarrhoea-causing MDR bacteria in the medical field with limited health care budgets.

JBP485, A Dual Inhibitor of Organic Anion Transporters (OATs) and Renal Dehydropeptidase-I (DHP-I), Protects Against Imipenem-Induced Nephrotoxicity.

Imipenem (IMP) possesses a broad spectrum of antibacterial activity; however, nephrotoxicity limits its clinical application in patients with renal insufficiency. In our previous studies, a dipeptide, JBP485, a dipeptide with the chemical structure cyclo-trans-4-L-hydroxyprolyl-L-serine, was found to attenuate drug-induced kidney injury. The current study aimed to explore whether JBP485 could relieve IMP-induced kidney injury and clarify the potential molecular pharmacokinetic mechanism. The effects of JBP485 on IMP nephrotoxicity were evaluated in rabbits and human kidney 2 (HK-2) cells. Drug-drug interactions (DDIs) mediated by organic anion transporters (OATs) and dehydropeptidase-I (DHP-I) were explored through pharmacokinetic studies in rats, metabolism assays in the kidney, and uptake studies in OAT-over-expressing cells. The results revealed that JBP485 significantly ameliorated IMP-induced nephrotoxicity in rabbits. Further, incubation of HK-2 cells with JBP485 or cilastatin markedly improved the cell survival rate, inhibited apoptosis and attenuated mitochondrial damage by improving the stability of IMP and reducing its intracellular accumulation. This suggests that DHP-I and OATs might be involved in the protective effect of JBP485. Furthermore, coadministration with JBP485 significantly increased the IMP’s plasma concentration as well as the area under the plasma concentration-time curve (AUC), while decreasing IMP renal clearance and cumulative urinary excretion. Moreover, JBP485 reduced IMP uptake in kidney slices and OAT1/3-human embryonic kidney 293 (HEK293) cells. At the same time, the metabolism of IMP by DHP-I was inhibited by JBP485 with an IC50 value of 12.15 ± 1.22 μM. Finally, the molecular docking assay revealed a direct interaction between JBP485 and OAT1/3 or DHP-I. In conclusion, JBP485 protected against IMP nephrotoxicity in rabbits and HK-2 cells by improving IMP stability and reducing its intracellular accumulation via simultaneous inhibition of renal OATs and DHP-I. JBP485 is a promising renoprotective agent and could serve as an effective supplement to reduce IMP-induced adverse renal reactions in the clinical setting.

Comparative genomics analysis of Bacillus velezensis LOH112 isolated from a nonagenarian provides insights into its biocontrol and probiotic traits

Bacillus velezensis has recently received increasing attention as a biological fungicide and a potential probiotic agent because of its broad spectrum of antibacterial and antifungal activities. Here, we evaluated the beneficial traits of a newly isolated B. velezensis strain LOH112 using comprehensive bioinformatics and comparative genomic analyses and in vitro experimental approaches. Whole genome sequencing and assembly results showed that the genome of LOH112 consists of a circular chromosome and a circular plasmid, which encodes proteins involved in important biological processes such as sporulation, quorum sensing, and antibiotic synthesis. LOH112 contains 13 secondary metabolism gene clusters responsible for the production of antimicrobial compounds. In vitro experiments showed that LOH112 effectively inhibits several fungi and Gram-positive pathogenic bacteria, hydrolyzes protein and cellulose, and is capable of forming strong adhesive biofilms. Furthermore, comparative genomics revealed that LOH112 contains 34 strain-specific orthologous gene clusters, including two caseinolytic protease P (clpP) genes responsible for proteomic homeostasis. Selective pressure analysis indicated that the transmembrane transporter and ATP-dependent alanine/valine adenylase genes were strongly positively selected, which may endow LOH112 with better biocontrol ability and potential probiotic properties. Collectively, these results not only provide insights into a deeper understanding of the genomic characterization of LOH112 but also imply the potential application of LOH112 as biocontrol and probiotic agents.

Isolation and characterization of a norfloxacin-degrading bacterial strain Aeromonas hydrophila sp. N215-1

Norfloxacin, a third-generation fluoroquinolone antibiotic, is increasingly used in the treatment of human and animal diseases, and being frequently detected in the environment. Norfloxacin has a broad spectrum of antibacterial activity, so few bacteria can degrade norfloxacin effectively. This is the first report on norfloxacin biodegradation by Aeromonas hydrophila sp. N215-1. Response surface methodology was employed to optimize the bacterial growth and degradation of norfloxacin of strain N215-1 in flask scale. The maximum yield of 0.31 in OD60f0 and 25.0% in degradation efficiency in 24 h were obtained when using RSM optimized medium, which improved strain growth and degradation by 3.88 and 5.68-fold, respectively. The kinetic analysis indicated that strain N215-1 could grow with the maximum specific growth rate, inhibit constant (Ki) and semi-saturation (Ks) constant of 0.2640/h, 23.9909 mg/L and 1.9817 mg/L, respectively. Furthermore, the optimized medium was applied in an 85 L modified AAO reactor with 2% N215-1 bioaugmentation, an increased norfloxacin removal rate from 56.0% to 81.2% was achieved. This study highlights a significant potential of using microbial co-metabolic culture for microbial remedied of norfloxacin-contaminated environments.

Nanoparticles of Bioactive Metals/Metal Oxides and Their Nanocomposites with Antibacterial Drugs for Biomedical Applications.

The increasing appearance of new strains of microorganisms resistant to the action of existing antibiotics is a modern problem that requires urgent decision. A promising potential solution is the use of nanoparticles of bioactive metals and their oxides as new antibacterial agents, since they are capable of affecting pathogenic microorganisms by mechanisms different from the mechanisms of action of antibiotics. Inorganic nanoparticles possess a wide spectrum of antibacterial activity. These particles can be easily conjugated with drug molecules and become carriers in targeted drug-delivery systems. This paper discusses the benefits and prospects of the application of nanoparticles from metals and metal oxides and their nanocomposites with antibacterial drugs.