glycopeptide antibiotics
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2022 ◽  
Vol 2 ◽  
Author(s):  
Jennifer Gerke ◽  
Anna M. Köhler ◽  
Jan-Peer Wennrich ◽  
Verena Große ◽  
Lulu Shao ◽  
...  

The soil microbiome comprises numerous filamentous fungi and bacteria that mutually react and challenge each other by the production of bioactive secondary metabolites. Herein, we show in liquid co-cultures that the presence of filamentous Streptomycetes producing antifungal glycopeptide antibiotics induces the production of the antibacterial and iron-chelating tropolones anhydrosepedonin (1) and antibiotic C (2) in the mold Aspergillus nidulans. Additionally, the biosynthesis of the related polyketide tripyrnidone (5) was induced, whose novel tricyclic scaffold we elucidated by NMR and HRESIMS data. The corresponding biosynthetic polyketide synthase-encoding gene cluster responsible for the production of these compounds was identified. The tropolones as well as tripyrnidone (5) are produced by genes that belong to the broad reservoir of the fungal genome for the synthesis of different secondary metabolites, which are usually silenced under standard laboratory conditions. These molecules might be part of the bacterium-fungus competition in the complex soil environment, with the bacterial glycopeptide antibiotic as specific environmental trigger for fungal induction of this cluster.


2021 ◽  
Vol 23 (1) ◽  
pp. 304
Author(s):  
Felipe López-Saucedo ◽  
Jesús Eduardo López-Barriguete ◽  
Guadalupe Gabriel Flores-Rojas ◽  
Sharemy Gómez-Dorantes ◽  
Emilio Bucio

Surface modification of polypropylene (PP) films was achieved using gamma-irradiation-induced grafting to provide an adequate surface capable of carrying glycopeptide antibiotics. The copolymer was obtained following a versatile two-step route; pristine PP was exposed to gamma rays and grafted with methyl methacrylate (MMA), and afterward, the film was grafted with N-vinylimidazole (NVI) by simultaneous irradiation. Characterization included Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), and physicochemical analysis of swelling and contact angle. The new material (PP-g-MMA)-g-NVI was loaded with vancomycin to quantify the release by UV-vis spectrophotometry at different pH. The surface of (PP-g-MMA)-g-NVI exhibited pH-responsiveness and moderate hydrophilicity, which are suitable properties for controlled drug release.


Antibiotics ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1533
Author(s):  
Andrés Andreo-Vidal ◽  
Elisa Binda ◽  
Victor Fedorenko ◽  
Flavia Marinelli ◽  
Oleksandr Yushchuk

The spread of antimicrobial resistance (AMR) creates a challenge for global health security, rendering many previously successful classes of antibiotics useless. Unfortunately, this also includes glycopeptide antibiotics (GPAs), such as vancomycin and teicoplanin, which are currently being considered last-resort drugs. Emerging resistance towards GPAs risks limiting the clinical use of this class of antibiotics—our ultimate line of defense against multidrug-resistant (MDR) Gram-positive pathogens. But where does this resistance come from? It is widely recognized that the GPA resistance determinants—van genes—might have originated from GPA producers, such as soil-dwelling Gram-positive actinobacteria, that use them for self-protection. In the current work, we present a comprehensive bioinformatics study on the distribution and phylogeny of GPA resistance determinants within the Actinobacteria phylum. Interestingly, van-like genes (vlgs) were found distributed in different arrangements not only among GPA-producing actinobacteria but also in the non-producers: more than 10% of the screened actinobacterial genomes contained one or multiple vlgs, while less than 1% encoded for a biosynthetic gene cluster (BGC). By phylogenetic reconstructions, our results highlight the co-evolution of the different vlgs, indicating that the most diffused are the ones coding for putative VanY carboxypeptidases, which can be found alone in the genomes or associated with a vanS/R regulatory pair.


Author(s):  
Yash Acharya ◽  
Shaown Bhattacharyya ◽  
Geetika Dhanda ◽  
Jayanta Haldar

2021 ◽  
Vol 12 ◽  
Author(s):  
Francesca Berini ◽  
Viviana Teresa Orlandi ◽  
Federica Gamberoni ◽  
Eleonora Martegani ◽  
Ilaria Armenia ◽  
...  

In the era of antimicrobial resistance, the use of nanoconjugated antibiotics is regarded as a promising approach for preventing and fighting infections caused by resistant bacteria, including those exacerbated by the formation of difficult-to-treat bacterial biofilms. Thanks to their biocompatibility and magnetic properties, iron oxide nanoparticles (IONPs) are particularly attractive as antibiotic carriers for the targeting therapy. IONPs can direct conjugated antibiotics to infection sites by the use of an external magnet, facilitating tissue penetration and disturbing biofilm formation. As a consequence of antibiotic localization, a decrease in its administration dosage might be possible, reducing the side effects to non-targeted organs and the risk of antibiotic resistance spread in the commensal microbiota. Here, we prepared nanoformulations of the ‘last-resort’ glycopeptides teicoplanin and vancomycin by conjugating them to IONPs via surface functionalization with (3-aminopropyl) triethoxysilane (APTES). These superparamagnetic NP-TEICO and NP-VANCO were chemically stable and NP-TEICO (better than NP-VANCO) conserved the typical spectrum of antimicrobial activity of glycopeptide antibiotics, being effective against a panel of staphylococci and enterococci, including clinical isolates and resistant strains. By a combination of different methodological approaches, we proved that NP-TEICO and, although to a lesser extent, NP-VANCO were effective in reducing biofilm formation by three methicillin-sensitive or resistant Staphylococcus aureus strains. Moreover, when attracted and concentrated by the action of an external magnet, NP-TEICO exerted a localized inhibitory effect on S. aureus biofilm formation at low antibiotic concentration. Finally, we proved that the conjugation of glycopeptide antibiotics to IONPs reduced their intrinsic cytotoxicity toward a human cell line.


2021 ◽  
Vol 96 (6) ◽  
pp. 463-477
Author(s):  
Si-Ho Kim ◽  
Soo-Youn Lee ◽  
Cheol-In Kang

Vancomycin and teicoplanin are representative glycopeptide antibiotics with activities against gram-positive cocci. The area under the drug concentration–time curve (AUC)/minimal inhibitory concentration (MIC) has been extensively used as an indicator of the bacteriological response to glycopeptide antibiotics, and the trough concentration has been used as a surrogate marker for the AUC/MIC. However, the guidelines for therapeutic drug monitoring (TDM) are being revised in accordance with increasing pharmacokinetic understanding of glycopeptide antibiotics. This review describes the pharmacokinetic/pharmacodynamic characteristics of glycopeptide antibiotics and discusses their optimal use with appropriate TDM.


2021 ◽  
Vol 14 (11) ◽  
pp. 1182
Author(s):  
Vladimir Vimberg ◽  
Leona Zieglerova ◽  
Aninda Mazumdar ◽  
Zsolt Szűcs ◽  
Aniko Borbás ◽  
...  

The increase in antibiotic resistance among Gram-positive bacteria underscores the urgent need to develop new antibiotics. New antibiotics should target actively growing susceptible bacteria that are resistant to clinically accepted antibiotics including bacteria that are not growing or are protected in a biofilm environment. In this paper, we compare the in vitro activities of two new semisynthetic glycopeptide antibiotics, MA79 and ERJ390, with two clinically used glycopeptide antibiotics—vancomycin and teicoplanin. The new antibiotics effectively killed not only exponentially growing cells of Staphylococcus aureus, but also cells in the stationary growth phase and biofilm.


2021 ◽  
Vol 2 ◽  
pp. 9-16
Author(s):  
Nicoleta Blebea ◽  
Gabriela Mitea

INTRODUCTION: Due to the rapid outbreak of the pandemic that causes SARS-CoV-2 infection and the increased rate of morbidity and mortality as a result of this new infection, the treatments pursued in therapy must have an increased potential to inhibit the replication of this virus. OBJECTIVES: The main objective of this article was to describe the most current drug therapies and their mechanisms of action used in the treatment of COVID-19. In this article, we have collected the latest information and multilingual international scientific discoveries about the treatment of COVID-19. RESULTS: Several compounds can be used to treat COVID-19 in order to reduce the duration of the disease and the rate of infection, to reduce the viral load, to prevent tissue damage, to stimulate the maturation of many cells, including immune cells in the human body and to reduce its severe symptoms. The most effective treatments were based on the antiviral drugs, antimalarial drugs, anti-inflammatory drugs, analgesics drugs, glycopeptide antibiotics, anticoagulants, vitamin C and vitamin D. The simplest and most direct approach to controlling SARS-CoV-2 outbreaks is the use of passive antibodies transferred from plasma to convalescent patients. Recently, studies have been completed for several vaccines that are approved against SARS-CoV-2. CONCLUSION: Scientists around the world are collaborating and innovating to make tests, treatments and vaccines available to the public that will save lives collectively and end this pandemic.


Author(s):  
Kai Liu ◽  
Xin-Rui Hu ◽  
Li-Xing Zhao ◽  
Yemin Wang ◽  
Zixin Deng ◽  
...  

Amycolatopsis sp. TNS106 harbors a ristomycin biosynthetic gene cluster ( asr ) in its genome and produces ristomycin A. Deletion of the sole cluster-situated StrR family regulatory gene asrR abolished the ristomycin A production and the transcription of asr genes orfs5 - 39 . Ristomycin A fermentation titer in Amycolatopsis sp. TNS106 was dramatically improved by overexpression of asrR and a heterologous StrR family regulatory gene bbr from the balhimycin BGC utilizing strong promoters and multiple gene copies. Ristomycin A production was improved by approximately 60-fold, resulting in fermentation titer of 4.01 g/L in flask culture, in one of the engineered strains. Overexpression of AsrR and Bbr upregulated transcription of tested asr biosynthetic genes, indicating that these asr genes were positively regulated by AsrR and Bbr. However, only the promoter region of the asrR -operon and the intergenic region upstream of orf12 were bound by AsrR and Bbr in gel retardation assays, suggesting that AsrR and Bbr directly regulated the asrR -operon and probably orfs12 - 14 , but no other asr biosynthetic genes. Further assays with synthetic short probes showed that AsrR and Bbr specifically bound not only probes containing the canonical inverted repeats but also a probe with only one 7-bp element of the inverted repeats in its native context. AsrR and Bbr have an N-terminal ParB-like domain and a central winged helix-turn-helix DNA-binding domain. Site-directed mutations indicated that the N-terminal ParB-like domain was involved in activation of ristomycin A biosynthesis and did not affect the DNA-binding activity of AsrR and Bbr. IMPORTANCE This study showed that overexpression of either native StrR family regulator (AsrR) or heterologous StrR family regulator (Bbr) dramatically improved ristomycin A production through increasing the transcription of biosynthetic genes directly or indirectly. The conserved ParB-like domain of AsrR and Bbr was demonstrated to be involved in the regulation of asr BGC expression. These findings provide new insights into the mechanism of StrR family regulators in the regulation of glycopeptide antibiotics biosynthesis. Furthermore, the regulators overexpression plasmids constructed in this study could serve as valuable tools for future utilization in strain improvement and genome mining for new glycopeptide antibiotics. In addition, ristomycin A is a type III glycopeptide antibiotic clinically used as a diagnostic reagent due to its side effect. The overproduction strains engineered in this study are ideal material for industrial production of ristomycin A.


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