Role of lipopolysaccharides in potential applications of nanocarrier systems

2021 ◽  
Vol 27 ◽  
Author(s):  
Pravin Shende ◽  
Shubham Gupta
Keyword(s):  
Bacterial Infections ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Surrounding Environment ◽  
Recent Developments ◽  
Potential Applications ◽  
Immune Stimulants ◽  
Therapeutic Properties ◽  
Immunogenic Response

Background: Lipopolysaccharides (LPS) are considered the main molecular component in the outer membrane of gram-negative bacteria. The LPS molecule in the bacterial cell wall acts as a primary physical barrier and protects gram-negative bacteria from the surrounding environment. LPS (endotoxins) show immunomodulatory therapeutic properties as well as toxicity to the host cell, whereas potential applications encompass. Objective: This review article aims to describe the recent developments of lipopolysaccharides in nanocarrier systems for various applications such as vaccination, cancer chemotherapy and immune stimulants action. Different nanocarriers like cubosomes, niosomes, dendrimers and metal nanoparticles used in the delivery of actives are employed to decorate lipopolysaccharide molecules superficially. Methods: A narrative review of all the relevant papers known to the author was conducted. Conclusion: Commercially available lipid nanoparticles contribute to many advances as promising nanocarriers in cancer therapy and are used as a vaccine adjuvant by improving the immune response due to their properties such as size, shape, biocompatibility, and biodegradability. Whereas lipopolysaccharide-decorated nanoparticles change the host's tolerability and increase the effectiveness of molecule in cancer immunotherapy. These nanoconjugate systems enhance overall immunogenic response and effectiveness in vaccine immunotherapy and targeted therapy, not only limited to humans application but also for poultry and aquaculture. Newer opportunities using lipopolysaccharides for the treatment and management of diseases with unique characteristics like the presence of lipoprotein that act as an alternative for bacterial infections over conventional dosage forms.

scholarly journals Treatment Options for Carbapenem-resistant Gram-negative Bacterial Infections

2019 ◽  
Vol 69 (Supplement_7) ◽  
pp. S565-S575 ◽  
Author(s):  
Yohei Doi
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Clinical Development ◽  
Gram Negative Bacteria ◽  
First Line ◽  
Safe Alternative ◽  
New Agents ◽  
Gram Negative ◽  
Carbapenem Resistant

AbstractAntimicrobial resistance has become one of the greatest threats to public health, with rising resistance to carbapenems being a particular concern due to the lack of effective and safe alternative treatment options. Carbapenem-resistant gram-negative bacteria of clinical relevance include the Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacter baumannii, and more recently, Stenotrophomonas maltophilia. Colistin and tigecycline have been used as first-line agents for the treatment of infections caused by these pathogens; however, there are uncertainties regarding their efficacy even when used in combination with other agents. More recently, several new agents with activity against certain carbapenem-resistant pathogens have been approved for clinical use or are reaching late-stage clinical development. They include ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, plazomicin, eravacycline, and cefiderocol. In addition, fosfomycin has been redeveloped in a new intravenous formulation. Data regarding the clinical efficacy of these new agents specific to infections caused by carbapenem-resistant pathogens are slowly emerging and appear to generally favor newer agents over previous best available therapy. As more treatment options become widely available for carbapenem-resistant gram-negative infections, the role of antimicrobial stewardship will become crucial in ensuring appropriate and rationale use of these new agents.

scholarly journals Investigating colistin drug resistance: The role of high-throughput sequencing and bioinformatics

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 150 ◽  
Author(s):  
Dickson Aruhomukama ◽  
Ivan Sserwadda ◽  
Gerald Mboowa
Keyword(s):  
Antibiotic Resistance ◽  
High Throughput ◽  
Bacterial Infections ◽  
High Throughput Sequencing ◽  
Health Concern ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Colistin Resistance ◽  
Gram Negative

Bacterial infections involving antibiotic resistant gram-negative bacteria continue to increase and represent a major global public health concern. Resistance to antibiotics in these bacteria is mediated by chromosomal and/or acquired resistance mechanisms, these give rise to multi-drug resistant (MDR) or extensive drug resistant (XDR) bacterial strains. Most recently, a novel acquired plasmid mediated resistance mechanism to colistin, an antibiotic that had been set apart as the last resort antibiotic in the treatment of infections involving MDR and XDR gram-negative bacteria, has been reported. Plasmid mediated colistin resistant gram-negative bacteria have been described to be pan-drug resistant, implying a state devoid of alternative antibiotic therapeutic options. This review describes the evolution of antibiotic resistance to plasmid mediated colistin resistance, and discusses the potential role of high-throughput sequencing technologies, genomics and bioinformatics towards improving antibiotic resistance surveillance, the search for novel drug targets and precision antibiotic therapy focused at combating colistin resistance, and antimicrobial resistance as a whole.

scholarly journals Flavonoids as Inhibitors of Bacterial Efflux Pumps

Molecules ◽  
2021 ◽  
Vol 26 (22) ◽  
pp. 6904
Author(s):  
Martin Waditzer ◽  
Franz Bucar
Keyword(s):  
Bacterial Infections ◽  
Treatment Options ◽  
Plant Secondary Metabolites ◽  
Herbal Medicines ◽  
Efflux Pumps ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Plant Constituents ◽  
Kaempferol Glycosides

Flavonoids are widely occurring secondary plant constituents, and are abundant in vegetable and fruit diets as well as herbal medicines. Therapeutic treatment options for bacterial infections are limited due to the spread of antimicrobial resistances. Hence, in a number of studies during the last few years, different classes of plant secondary metabolites as resistance-modifying agents have been carried out. In this review, we present the role of flavonoids as inhibitors of bacterial efflux pumps. Active compounds could be identified in the subclasses of chalcones, flavan-3-ols, flavanones, flavones, flavonols, flavonolignans and isoflavones; by far the majority of compounds were aglycones, although some glycosides like kaempferol glycosides with p-coumaroyl acylation showed remarkable results. Staphylococcus aureus NorA pump was the focus of many studies, followed by mycobacteria, whereas Gram-negative bacteria are still under-investigated.

scholarly journals Investigating colistin drug resistance: The role of high-throughput sequencing and bioinformatics

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 150 ◽  
Author(s):  
Dickson Aruhomukama ◽  
Ivan Sserwadda ◽  
Gerald Mboowa
Keyword(s):  
Antibiotic Resistance ◽  
High Throughput ◽  
Bacterial Infections ◽  
High Throughput Sequencing ◽  
Health Concern ◽  
Gram Negative Bacteria ◽  
Drug Resistant ◽  
Colistin Resistance ◽  
Gram Negative

Bacterial infections involving antibiotic-resistant gram-negative bacteria continue to increase and represent a major global public health concern. Resistance to antibiotics in these bacteria is mediated by chromosomal and/or acquired resistance mechanisms, these give rise to multi-drug resistant (MDR), extensive-drug resistant (XDR) or pan-drug resistant (PDR) bacterial strains. Most recently, plasmid-mediated resistance to colistin, an antibiotic that had been set apart as the last resort antibiotic in the treatment of infections involving MDR, XDR and PDR gram-negative bacteria has been reported. Plasmid-mediated colistin resistant gram-negative bacteria have been described to be PDR, implying a state devoid of alternative antibiotic therapeutic options. This review concisely describes the evolution of antibiotic resistance to plasmid-mediated colistin resistance and discusses the potential role of high-throughput sequencing technologies, genomics, and bioinformatics towards improving antibiotic resistance surveillance, the search for novel drug targets and precision antibiotic therapy focused at combating colistin resistance, and antibiotic resistance as a whole.

Synthesis, In Vitro and In Silico Studies of Indolequinone Derivatives against Clinically Relevant Bacterial Pathogens

2020 ◽  
Vol 20 (3) ◽  
pp. 192-208 ◽  
Author(s):  
Talita Odriane Custodio Leite ◽  
Juliana Silva Novais ◽  
Beatriz Lima Cosenza de Carvalho ◽  
Vitor Francisco Ferreira ◽  
Leonardo Alves Miceli ◽  
...  
Keyword(s):  
In Silico ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Mass Spectrometry Analysis ◽  
World Health ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Dione Derivative ◽  
In Silico Studies

Background: According to the World Health Organization, antimicrobial resistance is one of the most important public health threats of the 21st century. Therefore, there is an urgent need for the development of antimicrobial agents with new mechanism of action, especially those capable of evading known resistance mechanisms. Objective: We described the synthesis, in vitro antimicrobial evaluation, and in silico analysis of a series of 1H-indole-4,7-dione derivatives. Methods: The new series of 1H-indole-4,7-diones was prepared with good yield by using a copper(II)- mediated reaction between bromoquinone and β-enamino ketones bearing alkyl or phenyl groups attached to the nitrogen atom. The antimicrobial potential of indole derivatives was assessed. Molecular docking studies were also performed using AutoDock 4.2 for Windows. Characterization of all compounds was confirmed by one- and two-dimensional NMR techniques 1H and 13C NMR spectra [1H, 13C – APT, 1H x 1H – COSY, HSQC and HMBC], IR and mass spectrometry analysis. Results: Several indolequinone compounds showed effective antimicrobial profile against Grampositive (MIC = 16 µg.mL-1) and Gram-negative bacteria (MIC = 8 µg.mL-1) similar to antimicrobials current on the market. The 3-acetyl-1-(2,5-dimethylphenyl)-1H-indole-4,7-dione derivative exhibited an important effect against different biofilm stages formed by a serious hospital life-threatening resistant strain of Methicillin-Resistant Staphylococcus aureus (MRSA). A hemocompatibility profile analysis based on in vitro hemolysis assays revealed the low toxicity effects of this new series. Indeed, in silico studies showed a good pharmacokinetics and toxicological profiles for all indolequinone derivatives, reinforcing their feasibility to display a promising oral bioavailability. An elucidation of the promising indolequinone derivatives binding mode was achieved, showing interactions with important sites to biological activity of S. aureus DNA gyrase. These results highlighted 3-acetyl-1-(2-hydroxyethyl)-1Hindole- 4,7-dione derivative as broad-spectrum antimicrobial prototype to be further explored for treating bacterial infections. Conclusion: The highly substituted indolequinones were obtained in moderate to good yields. The pharmacological study indicated that these compounds should be exploited in the search for a leading substance in a project aimed at obtaining new antimicrobials effective against Gram-negative bacteria.

scholarly journals The antimicrobial potential of cannabidiol

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Mark A. T. Blaskovich ◽  
Angela M. Kavanagh ◽  
Alysha G. Elliott ◽  
Bing Zhang ◽  
Soumya Ramu ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Modern Medicine ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
New Class ◽  
Clostridioides Difficile ◽  
Excellent Activity ◽  
Induce Resistance ◽  
First Time

AbstractAntimicrobial resistance threatens the viability of modern medicine, which is largely dependent on the successful prevention and treatment of bacterial infections. Unfortunately, there are few new therapeutics in the clinical pipeline, particularly for Gram-negative bacteria. We now present a detailed evaluation of the antimicrobial activity of cannabidiol, the main non-psychoactive component of cannabis. We confirm previous reports of Gram-positive activity and expand the breadth of pathogens tested, including highly resistant Staphylococcus aureus, Streptococcus pneumoniae, and Clostridioides difficile. Our results demonstrate that cannabidiol has excellent activity against biofilms, little propensity to induce resistance, and topical in vivo efficacy. Multiple mode-of-action studies point to membrane disruption as cannabidiol’s primary mechanism. More importantly, we now report for the first time that cannabidiol can selectively kill a subset of Gram-negative bacteria that includes the ‘urgent threat’ pathogen Neisseria gonorrhoeae. Structure-activity relationship studies demonstrate the potential to advance cannabidiol analogs as a much-needed new class of antibiotics.

scholarly journals Extracellular Vesicles: Novel Opportunities to Understand and Detect Neoplastic Diseases

2021 ◽  
pp. 030098582199932
Author(s):  
Laura Bongiovanni ◽  
Anneloes Andriessen ◽  
Marca H. M. Wauben ◽  
Esther N. M. Nolte-’t Hoen ◽  
Alain de Bruin
Keyword(s):  
Extracellular Vesicles ◽  
Biologically Active ◽  
Liquid Biopsies ◽  
Donor Cells ◽  
Recent Developments ◽  
Veterinary Pathology ◽  
Cell Components ◽  
Potential Applications ◽  
Intercellular Communications

With a size range from 30 to 1000 nm, extracellular vesicles (EVs) are one of the smallest cell components able to transport biologically active molecules. They mediate intercellular communications and play a fundamental role in the maintenance of tissue homeostasis and pathogenesis in several types of diseases. In particular, EVs actively contribute to cancer initiation and progression, and there is emerging understanding of their role in creation of the metastatic niche. This fact underlies the recent exponential growth in EV research, which has improved our understanding of their specific roles in disease and their potential applications in diagnosis and therapy. EVs and their biomolecular cargo reflect the state of the diseased donor cells, and can be detected in body fluids and exploited as biomarkers in cancer and other diseases. Relatively few studies have been published on EVs in the veterinary field. This review provides an overview of the features and biology of EVs as well as recent developments in EV research including techniques for isolation and analysis, and will address the way in which the EVs released by diseased tissues can be studied and exploited in the field of veterinary pathology. Uniquely, this review emphasizes the important contribution that pathologists can make to the field of EV research: pathologists can help EV scientists in studying and confirming the role of EVs and their molecular cargo in diseased tissues and as biomarkers in liquid biopsies.

scholarly journals MexAB-OprM Efflux Pump Interaction with the Peptidoglycan of Escherichia coli and Pseudomonas aeruginosa

2021 ◽  
Vol 22 (10) ◽  
pp. 5328
Author(s):  
Miao Ma ◽  
Margaux Lustig ◽  
Michèle Salem ◽  
Dominique Mengin-Lecreulx ◽  
Gilles Phan ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Cell Division ◽  
Membrane Proteins ◽  
Outer Membrane ◽  
Efflux Pump ◽  
Gram Negative Bacteria ◽  
Gram Negative ◽  
Active Efflux

One of the major families of membrane proteins found in prokaryote genome corresponds to the transporters. Among them, the resistance-nodulation-cell division (RND) transporters are highly studied, as being responsible for one of the most problematic mechanisms used by bacteria to resist to antibiotics, i.e., the active efflux of drugs. In Gram-negative bacteria, these proteins are inserted in the inner membrane and form a tripartite assembly with an outer membrane factor and a periplasmic linker in order to cross the two membranes to expulse molecules outside of the cell. A lot of information has been collected to understand the functional mechanism of these pumps, especially with AcrAB-TolC from Escherichia coli, but one missing piece from all the suggested models is the role of peptidoglycan in the assembly. Here, by pull-down experiments with purified peptidoglycans, we precise the MexAB-OprM interaction with the peptidoglycan from Escherichia coli and Pseudomonas aeruginosa, highlighting a role of the peptidoglycan in stabilizing the MexA-OprM complex and also differences between the two Gram-negative bacteria peptidoglycans.

scholarly journals Regulation of Plant Mineral Nutrition by Signal Molecules

2021 ◽  
Vol 9 (4) ◽  
pp. 774
Author(s):  
Vipin Chandra Kalia ◽  
Chunjie Gong ◽  
Sanjay K. S. Patel ◽  
Jung-Kul Lee
Keyword(s):  
Signal Molecules ◽  
Gram Negative Bacteria ◽  
Human Beings ◽  
High Cell ◽  
Specific Chemical ◽  
Gram Negative ◽  
Plant Mineral Nutrition ◽  
Recent Developments ◽  
Cell Densities ◽  
Metabolic Activities

Microbes operate their metabolic activities at a unicellular level. However, it has been revealed that a few metabolic activities only prove beneficial to microbes if operated at high cell densities. These cell density-dependent activities termed quorum sensing (QS) operate through specific chemical signals. In Gram-negative bacteria, the most widely reported QS signals are acylhomoserine lactones. In contrast, a novel QS-like system has been elucidated, regulating communication between microbes and plants through strigolactones. These systems regulate bioprocesses, which affect the health of plants, animals, and human beings. This mini-review presents recent developments in the QS and QS-like signal molecules in promoting plant health.

The role of Gram-negative bacteria in skin and soft tissue infections

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Alessandro Russo ◽  
Enrico Maria Trecarichi ◽  
Carlo Torti
Keyword(s):  
Soft Tissue ◽  
Gram Negative Bacteria ◽  
Soft Tissue Infections ◽  
Gram Negative
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