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Science Advances Sep 2021Strigolactones (SLs) are a class of phytohormones playing diverse roles in plant growth and development, yet the limited access to SLs is largely impeding SL-based...
Strigolactones (SLs) are a class of phytohormones playing diverse roles in plant growth and development, yet the limited access to SLs is largely impeding SL-based foundational investigations and applications. Here, we developed – consortia to establish a microbial biosynthetic platform for the synthesis of various SLs, including carlactone, carlactonoic acid, 5-deoxystrigol (5DS; 6.65 ± 1.71 μg/liter), 4-deoxyorobanchol (3.46 ± 0.28 μg/liter), and orobanchol (OB; 19.36 ± 5.20 μg/liter). The SL-producing platform enabled us to conduct functional identification of CYP722Cs from various plants as either OB or 5DS synthase. It also allowed us to quantitatively compare known variants of plant SL biosynthetic enzymes in the microbial system. The titer of 5DS was further enhanced through pathway engineering to 47.3 μg/liter. This work provides a unique platform for investigating SL biosynthesis and evolution and lays the foundation for developing SL microbial production process.
PubMed: 34533983
DOI: 10.1126/sciadv.abh4048 -
RSC Advances Jul 2020Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of operations that can... (Review)
Review
Droplet-based microfluidic systems have been shown to be compatible with many chemical and biological reagents and capable of performing a variety of operations that can be rendered programmable and reconfigurable. This platform has dimensional scaling benefits that have enabled controlled and rapid mixing of fluids in the droplet reactors, resulting in decreased reaction times. This, coupled with the precise generation and repeatability of droplet operations, has made the droplet-based microfluidic system a potent high throughput platform for biomedical research and applications. In addition to being used as micro-reactors ranging from the nano- to femtoliter (10 liters) range; droplet-based systems have also been used to directly synthesize particles and encapsulate many biological entities for biomedicine and biotechnology applications. For this, in the following article we will focus on the various droplet operations, as well as the numerous applications of the system and its future in many advanced scientific fields. Due to advantages of droplet-based systems, this technology has the potential to offer solutions to today's biomedical engineering challenges for advanced diagnostics and therapeutics.
PubMed: 35516933
DOI: 10.1039/d0ra04566g -
Saudi Journal of Biological Sciences Jan 2021Microbial surfactants are amphipathic molecules that consist of hydrophilic and hydrophobic domains, which allow partition of two fluid phases of varying degree of... (Review)
Review
Microbial surfactants are amphipathic molecules that consist of hydrophilic and hydrophobic domains, which allow partition of two fluid phases of varying degree of polarity. They are classified into two main groups: bioemulsifier and biosurfactant, depending on their molecular weight. Microbial surfactants occur in various categories according to their chemical nature and producing organisms. These biomolecules are produced by diverse groups of microorganisms including fungi, bacteria, and yeasts. Their production is significantly influenced by substrate type, fermentation technology and microbial strains. Owing to inherent multifunctional properties and assorted synthetic aptitude of the microbes, microbial surfactants are mostly preferred than their chemical counterparts for various industrial and biomedical applications including bioremediation, oil recovery; as supplements in laundry formulations and as emulsion-stabilizers in food and cosmetic industries as well as therapeutic agents in medicine. The present review discusses on production of microbial surfactants as promising and alternative broad-functional biomolecules for various biotechnological applications.
PubMed: 33424354
DOI: 10.1016/j.sjbs.2020.10.058 -
Antimicrobial Agents and Chemotherapy Feb 2021The objectives of this study were to characterize the role of the , , and genes in fosfomycin resistance in and evaluate the use of sodium phosphonoformate (PPF) in...
The objectives of this study were to characterize the role of the , , and genes in fosfomycin resistance in and evaluate the use of sodium phosphonoformate (PPF) in combination with fosfomycin. Seven clinical isolates of and the reference strain (ATCC 700721) were used, and their genomes were sequenced. Δ, Δ, and Δ mutants were constructed from two isolates and ATCC 700721. Fosfomycin susceptibility testing was done by the gradient strip method. Synergy between fosfomycin and PPF was studied by checkerboard assay and analyzed using SynergyFinder. Spontaneous fosfomycin mutant frequencies at 64 and 512 mg/liter, activity using growth curves with fosfomycin gradient concentrations (0 to 256mg/liter), and time-kill assays at 64 and 307 mg/liter were evaluated with and without PPF (0.623 mM). The MICs of fosfomycin against the clinical isolates ranged from 16 to ≥1,024 mg/liter. The addition of 0.623 mM PPF reduced fosfomycin MIC between 2- and 8-fold. Deletion of led to a 32-fold decrease. Synergistic activities were observed with the combination of fosfomycin and PPF (most synergistic area at 0.623 mM). The lowest fosfomycin-resistant mutant frequencies were found in Δ mutants, with decreases in frequency from 1.69 × 10 to 1.60 × 10 for 64 mg/liter of fosfomycin. In the final growth monitoring and time-kill assays, fosfomycin showed a bactericidal effect only with the deletion of and not with the addition of PPF. We conclude that gene inactivation leads to a decrease in fosfomycin resistance in The pharmacological approach using PPF did not achieve enough activity, and the effect decreased with the presence of fosfomycin-resistant mutations.
Topics: Anti-Bacterial Agents; Foscarnet; Fosfomycin; Klebsiella pneumoniae; Microbial Sensitivity Tests; beta-Lactamases
PubMed: 33361305
DOI: 10.1128/AAC.01911-20 -
Antimicrobial Agents and Chemotherapy Nov 2022We evaluated the activity of manogepix and comparator agents against 1,435 contemporary fungal isolates collected worldwide from 73 medical centers in North America,...
We evaluated the activity of manogepix and comparator agents against 1,435 contemporary fungal isolates collected worldwide from 73 medical centers in North America, Europe, the Asia-Pacific region, and Latin America during 2020. Of the isolates tested, 74.7% were spp.; 3.7% were non- yeasts, including 27 Cryptococcus neoformans var. (1.9%); 17.1% were Aspergillus spp.; and 4.5% were other molds. All fungal isolates were tested by reference broth microdilution according to CLSI methods. Based on MIC values, manogepix (MIC/MIC, 0.008/0.06 mg/liter) was 16- to 64-fold more active than anidulafungin, micafungin, and fluconazole against spp. isolates and the most active agent tested. Similarly, manogepix (MIC/MIC, 0.5/1 mg/liter) was ≥8-fold more active than anidulafungin, micafungin, and fluconazole against C. neoformans var. . Based on minimum effective concentration for 90% of the isolates tested (MEC) and MIC values, manogepix (MEC, 0.03 mg/liter) was 16- to 64-fold more potent than itraconazole, posaconazole, and voriconazole (MICs, 0.5 to 2 mg/liter) against 246 Aspergillus spp. isolates. Aspergillus fumigatus isolates exhibited a wild-type (WT) phenotype for the mold-active triazoles, including itraconazole (87.0% WT) and voriconazole (96.4% WT). Manogepix was highly active against uncommon species of , non- yeasts, and rare molds, including 11 isolates of Candida auris (MIC/MIC, 0.004/0.015 mg/liter) and 12 isolates of spp. (MEC/MEC, 0.06/0.12 mg/liter). Additional studies are in progress to evaluate the clinical utility of the manogepix prodrug fosmanogepix in difficult-to-treat resistant fungal infections.
Topics: Anidulafungin; Micafungin; Fluconazole; Voriconazole; Itraconazole; Microbial Sensitivity Tests; Antifungal Agents; Candida; Aspergillus; Cryptococcus neoformans; Drug Resistance, Fungal
PubMed: 36286491
DOI: 10.1128/aac.01028-22 -
Anaesthesiology Intensive Therapy 2017Guidelines for infusion fluid therapy rarely take into account that adverse effects occur in a dose-dependent fashion. Adverse effects of crystalloid fluids are related... (Review)
Review
Guidelines for infusion fluid therapy rarely take into account that adverse effects occur in a dose-dependent fashion. Adverse effects of crystalloid fluids are related to their preferential distribution to the interstitium of the subcutis, the gut, and the lungs. The gastrointestinal recovery time is prolonged by 2 days when more than 2 litres is administered. Infusion of 6-7 litres during open abdominal surgery results in poor wound healing, pulmonary oedema, and pneumonia. There is also a risk of fatal postoperative pulmonary oedema that might develop several days after the surgery. Even larger amounts cause organ dysfunction by breaking up the interstitial matrix and allowing the formation of lacunae of fluid in the skin and central organs, such as the heart. Adverse effects of colloid fluids include anaphylactic reactions, which occur in 1 out of 500 infusions. The possibility that hydroxyethyl starch causes kidney injury in patients other than those with sepsis is still unclear. For both crystalloid and colloid fluids, coagulation becomes impaired when the induced haemodilution has reached 40%. Coagulopathy is aggravated by co-existing hypothermia. Although oedema can occur from both crystalloid and colloid fluids, these differ in pathophysiology. To balance fluid-induced adverse effects, this review suggests that a colloid fluid is indicated when the infused crystalloid volume exceeds 3-4 litres, plasma volume support is still needed, and the transfusion of blood products is not yet indicated.
Topics: Anaphylaxis; Colloids; Crystalloid Solutions; Dose-Response Relationship, Drug; Fluid Therapy; Humans; Hydroxyethyl Starch Derivatives; Isotonic Solutions; Plasma Volume; Postoperative Complications; Practice Guidelines as Topic; Tissue Distribution
PubMed: 28953310
DOI: 10.5603/AIT.a2017.0045 -
Microbiology Spectrum Feb 2022Acinetobacter baumannii has emerged globally as a difficult-to-treat nosocomial pathogen and become resistant to carbapenems, resulting in limited treatment options....
Acinetobacter baumannii has emerged globally as a difficult-to-treat nosocomial pathogen and become resistant to carbapenems, resulting in limited treatment options. KBP-7072 is a novel semisynthetic aminomethylcycline, expanded spectrum tetracycline antibacterial agent with completed phase 1 clinical development studies. This study aimed to evaluate the activity of KBP-7072 and several comparators against clinical A. baumannii isolates collected from China. A collection of 536 A. baumannii clinical isolates were isolated from 20 hospitals across 13 provinces and cities in China between 2018 and 2019. Antimicrobial susceptibility testing of 12 antimicrobial agents was performed utilizing the broth microdilution method recommended by CLSI. KBP-7072 has shown active antibacterial activity against 536 A. baumannii isolates. It inhibited the growth of all isolates at 4 mg/liter, including 372 carbapenem-resistant isolates, 37 tigecycline MIC ≥ 4 mg/liter isolates, and 138 omadacycline MIC ≥ 4 mg/liter isolates. Compared with other expanded spectrum tetracyclines, KBP-7072 (MIC, 1 mg/liter) outperformed 2-fold and 4-fold more active against 536 A. baumannii isolates than tigecycline (MIC, 2 mg/liter) and omadacycline (MIC, 4 mg/liter). KBP-7072 was as equally active as colistin (MIC, 1 mg/liter, 99.4% susceptible). Doxycycline (33.4% susceptible), gentamicin (31.3% susceptible), meropenem (30.6%, susceptible), imipenem (30.2% susceptible), ceftazidime (27.8% susceptible), piperacillin-tazobactam (27.2% susceptible), and levofloxacin (27.2% susceptible) showed marginally poor antibacterial activity against tested isolates according to CLSI breakpoints, except for minocycline (73.7% susceptible). KBP-7072 is a potential alternative agent for the treatment of infection caused by A. baumannii, including carbapenem-resistant species. It is reported that A. baumannii has emerged as an intractable nosocomial pathogen in hospitals especially when it develops resistance to carbapenems and other antibiotics, which limits treatment options and leads to high mortality. In February 2017, the WHO published a list of ESKAPE pathogens designated "priority status" for which new antibiotics are urgently needed. Therefore, the epidemiological surveillance and new therapeutic development of A. baumannii must be strengthened to confront an emerging global epidemic. KBP-7072 is a novel, expanded spectrum tetracycline antibacterial and has demonstrated good activity against recent geographically diverse A. baumannii isolates collected from North America, Europe, Latin America, and Asia-Pacific. This study has shown excellent activity of KBP-7072 against clinical A. baumannii isolates collected from different regions of China, regarded as supplementary to KBP-7072 pharmacodynamics data, which is of great significance, as it is promising an alternative treatment in CRAB isolates infections in China.
Topics: Acinetobacter Infections; Acinetobacter baumannii; Anti-Bacterial Agents; Carbapenems; China; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests; Tetracyclines; Tigecycline
PubMed: 35138143
DOI: 10.1128/spectrum.01471-21 -
Ultrasonics Sonochemistry Mar 2017In recent years the use of high frequency ultrasound standing waves (megasonics) for droplet or cell separation from biomass has emerged beyond the microfluidics scale... (Review)
Review
In recent years the use of high frequency ultrasound standing waves (megasonics) for droplet or cell separation from biomass has emerged beyond the microfluidics scale into the litre to industrial scale applications. The principle for this separation technology relies on the differential positioning of individual droplets or particles across an ultrasonic standing wave field within the reactor and subsequent biomass material predisposition for separation via rapid droplet agglomeration or coalescence into larger entities. Large scale transducers have been characterised with sonochemiluminescence and hydrophones to enable better reactor designs. High frequency enhanced separation technology has been demonstrated at industrial scale for oil recovery in the palm oil industry and at litre scale to assist olive oil, coconut oil and milk fat separation. Other applications include algal cell dewatering and milk fat globule fractionation. Frequency selection depends on the material properties and structure in the biomass mixture. Higher frequencies (1 and 2MHz) have proven preferable for better separation of materials with smaller sized droplets such as milk fat globules. For palm oil and olive oil, separation has been demonstrated within the 400-600kHz region, which has high radical production, without detectable impact on product quality.
Topics: Biomass; Chemical Fractionation; Glycolipids; Glycoproteins; Lipid Droplets; Microalgae; Plant Oils; Ultrasonic Waves
PubMed: 27217305
DOI: 10.1016/j.ultsonch.2016.04.032