scholarly journals Armeniaspirols inhibit the AAA+ proteases ClpXP and ClpYQ leading to cell division arrest in Gram-positive bacteria

2019 ◽  
Author(s):  
Puneet Labana ◽  
Mark H. Dornan ◽  
Matthew Lafrenière ◽  
Tomasz L. Czarny ◽  
Eric D. Brown ◽  
...  
Keyword(s):  
Cell Division ◽  
Mechanism Of Action ◽  
Modern Medicine ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Biologically Relevant ◽  
Gram Positive Bacteria ◽  
Drug Resistant Bacteria ◽  
New Antibiotics ◽  
Virulence Target

ABSTRACTMulti-drug resistant bacteria present an urgent threat to modern medicine, creating a desperate need for the discovery of antibiotics with new modes of action. Natural products whose unique highly diverse structures have been shaped by evolution to possess biologically relevant activity are an ideal discovery ground for new antibiotics with new mechanisms of action. In this study we elucidate the mechanism of action of the Gram-positive antibiotic armeniaspirol, a compound for which resistant bacteria could not be selected for. We show that armeniaspirol inhibits the ATP-dependent proteases ClpXP and ClpYQ in biochemical assays and in the Gram-positive bacteria Bacillus subtilis. We then show that this activity dysregulates key proteins involved in the divisome and elongasome including FtsZ, DivIVA, and MreB all of which are known to inhibit cell division when upregulated. Inhibition of ClpXP and ClpYQ leading to dysregulation of the divisome and elongasome represents a new mechanism of action and armeniaspirol is the first known natural product inhibitor of the coveted anti-virulence target ClpP. Thus armeniaspirol is the lead compound for a promising new class of antibiotics with a unique pharmacology and a novel mechanism for combating antimicrobial resistance, making it a highly promising candidate for further development.

scholarly journals Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2888 ◽  
Author(s):  
Buthaina Jubeh ◽  
Zeinab Breijyeh ◽  
Rafik Karaman
Keyword(s):  
Turning Point ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Medical Interventions ◽  
Gram Positive Bacteria ◽  
New Antibiotics ◽  
Vancomycin Resistant ◽  
New Treatments ◽  
Emergence Of Resistance

The discovery of antibiotics has created a turning point in medical interventions to pathogenic infections, but unfortunately, each discovery was consistently followed by the emergence of resistance. The rise of multidrug-resistant bacteria has generated a great challenge to treat infections caused by bacteria with the available antibiotics. Today, research is active in finding new treatments for multidrug-resistant pathogens. In a step to guide the efforts, the WHO has published a list of the most dangerous bacteria that are resistant to current treatments and requires the development of new antibiotics for combating the resistance. Among the list are various Gram-positive bacteria that are responsible for serious healthcare and community-associated infections. Methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium, and drug-resistant Streptococcus pneumoniae are of particular concern. The resistance of bacteria is an evolving phenomenon that arises from genetic mutations and/or acquired genomes. Thus, antimicrobial resistance demands continuous efforts to create strategies to combat this problem and optimize the use of antibiotics. This article aims to provide a review of the most critical resistant Gram-positive bacterial pathogens, their mechanisms of resistance, and the new treatments and approaches reported to circumvent this problem.

Antimicrobial Capacity of Plant Polyphenols against Gram-positive Bacteria: A Comprehensive Review

2020 ◽  
Vol 27 (15) ◽  
pp. 2576-2606 ◽  
Author(s):  
Francisco Javier Álvarez-Martínez ◽  
Enrique Barrajón-Catalán ◽  
José Antonio Encinar ◽  
Juan Carlos Rodríguez-Díaz ◽  
Vicente Micol
Keyword(s):  
Antimicrobial Activity ◽  
Antibacterial Activity ◽  
Mechanism Of Action ◽  
Molecular Targets ◽  
Membrane Receptors ◽  
Resistant Bacteria ◽  
Plant Polyphenols ◽  
Gram Positive ◽  
Gram Positive Bacteria ◽  
Promising Source

Background: Multi-drug-resistant bacteria such as Methicillin-Resistant Staphylococcus aureus (MRSA) disseminate rapidly amongst patients in healthcare facilities and suppose an increasingly important cause of community-associated infections and associated mortality. The development of effective therapeutic options against resistant bacteria is a public health priority. Plant polyphenols are structurally diverse compounds that have been used for centuries for medicinal purposes, including infections treatment and possess, not only antimicrobial activity, but also antioxidant, anti-inflammatory and anticancer activities among others. Based on the existing evidence on the polyphenols’ antibacterial capacity, polyphenols may be postulated as an alternative or complementary therapy for infectious diseases. Objective: To review the antimicrobial activity of plant polyphenols against Gram-positive bacteria, especially against S. aureus and its resistant strains. Determine the main bacterial molecular targets of polyphenols and their potential mechanism of action. Methodology: The most relevant reports on plant polyphenols’ antibacterial activity and their putative molecular targets were studied. We also performed virtual screening of thousand different polyphenols against proteins involved in the peptidoglycan biosynthesis to find potential valuable bioactive compounds. The bibliographic information used in this review was obtained from MEDLINE via PubMed. Results: Several polyphenols: phenolic acids, flavonoids (especially flavonols), tannins, lignans, stilbenes and combinations of these in botanical mixtures, have exhibited significant antibacterial activity against resistant and non-resistant Gram-positive bacteria at low μg/mL range MIC values. Their mechanism of action is quite diverse, targeting cell wall, lipid membrane, membrane receptors and ion channels, bacteria metabolites and biofilm formation. Synergic effects were also demonstrated for some combinations of polyphenols and antibiotics. Conclusion: Plant polyphenols mean a promising source of antibacterial agents, either alone or in combination with existing antibiotics, for the development of new antibiotic therapies.

scholarly journals Antimicrobial Activity of Microorganisms Isolated from Ant Nests of Lasius niger

Life ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 91
Author(s):  
Tatiana A. Efimenko ◽  
Alla A. Glukhova ◽  
Mariia V. Demiankova ◽  
Yuliya V. Boykova ◽  
Natalia D. Malkina ◽  
...  
Keyword(s):  
Antibiotic Activity ◽  
Lasius Niger ◽  
Resistant Bacteria ◽  
Similar Species ◽  
Gram Positive ◽  
Genus Streptomyces ◽  
Streptomyces Sp ◽  
Gram Positive Bacteria ◽  
Drug Resistant Bacteria

In this study, the microbial communities of two nests of black garden ants (Lasius niger) in the hollows of stem branches of old apple trees were found to have similar species compositions: each community contained representatives of three species from the Bacillaceae family and one species of actinomycetes from the genus Streptomyces. In total, four types of bacilli and two actinomycetes were isolated. Actinomycetes were identified as Streptomyces antibioticus-like and Streptomyces sp. None of the bacilli had antibiotic activity, whereas both streptomycetes produced antibiotics that inhibited the growth of Gram-positive bacteria in vitro, including isolates from their community. Antibiotic compounds of S. antibioticus-like strain INA 01148 (Institute of New Antibiotics) were identified as actinomycin D and its closest homologue, actinomycin A. Actinomycins presumably change the microbial community of the ant nest substrate as they act against Gram-positive bacteria and against fungi and Gram-negative bacteria. The antibiotic activity of the isolated Streptomyces sp. INA 01156 is of interest, since the substances produced by this strain inhibit the growth of drug-resistant bacteria, including methicillin-resistant Staphylococcus aureus INA 00761 (MRSA) and vancomycin-resistant strain Leuconostoc mesenteroides VKPM B-4177 (VR) (VKPM–National Collection of Industrial Microorganisms (Russian acronym)).

Novel Antibiotics from Marine Sources

2011 ◽  
Vol 4 (3) ◽  
pp. 1446-1461 ◽  
Author(s):  
E.A. Martis ◽  
G M Doshi ◽  
G V Aggarwal ◽  
P P Shanbhag
Keyword(s):  
Pharmaceutical Industry ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Terrestrial Life ◽  
New Antibiotics ◽  
Antibiotic Compounds ◽  
New Generation ◽  
Novel Antibiotics ◽  
Untapped Resource

With the emergence of newer diseases, resistant forms of infectious diseases and multi-drug resistant bacteria, it has become essential to develop novel and more effective antibiotics. Current antibiotics are obtained from terrestrial life or made synthetically from intermediates. The ocean represents virtually untapped resource from which novel antibiotic compounds can be discovered. It is the marine world that will provide the pharmaceutical industry with the next generation of antibiotics. Marine antibiotics are antibiotics obtained from marine organisms. Scientists have reported the discovery of various antibiotics from marine bacteria (aplasmomycin, himalomycins, and pelagiomycins), sponges (Ara C, variabillin, strobilin, ircinin-1, aeroplysin, 3,5-dibromo-4-hydroxyphenylacetamide), coelenterates (asperidol and eunicin), mollusks (laurinterol and pachydictyol), tunicates (geranylhydroquinone and cystadytins), algae (cycloeudesmol, aeroplysinin-1(+), prepacifenol and tetrabromoheptanone), worms (tholepin and 3,5-dibromo-4-hydroxybezaldehyde), and actinomycetes (marinomycins C and D). This indicates that the marine environment, representing approximately half of the global diversity, is an enormous resource for new antibiotics and this source needs to be explored for the discovery of new generation antibiotics. The present article provides an overview of various antibiotics obtained from marine sources.

scholarly journals Antibacterial Activity of Fluorobenzoylthiosemicarbazides and Their Cyclic Analogues with 1,2,4-Triazole Scaffold

Molecules ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 170
Author(s):  
Urszula Kosikowska ◽  
Monika Wujec ◽  
Nazar Trotsko ◽  
Wojciech Płonka ◽  
Piotr Paneth ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Resistant Bacteria ◽  
Binding Affinities ◽  
Substitution Pattern ◽  
Minimal Inhibitory Concentrations ◽  
Gram Positive Bacteria ◽  
Structure Activity ◽  
Drug Resistant Bacteria ◽  
Reference Strains

The development of drug-resistant bacteria is currently one of the major challenges in medicine. Therefore, the discovery of novel lead structures for the design of antibacterial drugs is urgently needed. In this structure–activity relationship study, a library of ortho-, meta-, and para-fluorobenzoylthiosemicarbazides, and their cyclic analogues with 1,2,4-triazole scaffold, was created and tested for antibacterial activity against Gram-positive bacteria strains. While all tested 1,2,4-triazoles were devoid of potent activity, the antibacterial response of the thiosemicarbazides was highly dependent on substitution pattern at the N4 aryl position. The optimum activity for these compounds was found for trifluoromethyl derivatives such as 15a, 15b, and 16b, which were active against both the reference strains panel, and pathogenic methicillin-sensitive and methicillin-resistant Staphylococcus aureus clinical isolates at minimal inhibitory concentrations (MICs) ranging from 7.82 to 31.25 μg/mL. Based on the binding affinities obtained from docking, the conclusion can be reached that fluorobenzoylthiosemicarbazides can be considered as potential allosteric d-alanyl-d-alanine ligase inhibitors.

scholarly journals UJI RESISTENSI BAKTERI BACILLUS SP YANG DIISOLASI DARI PLAK GIGI TERHADAP MERKURI DAN ERITROMISIN

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Terence Kanzil ◽  
Fatimawali . ◽  
Aaltje Manampiring
Keyword(s):  
Heavy Metal ◽  
Toxic Effects ◽  
Resistant Bacteria ◽  
Bacillus Sp ◽  
Gram Positive ◽  
Toxic Heavy Metal ◽  
Mer Operon ◽  
Dental Fillings ◽  
Gram Positive Bacteria ◽  
Mercury Resistant Bacteria

Abstract: Mercury is a toxic heavy metal that is used for dental fillings in the form of amalgam. To reduce the toxic effects produced by mercury, mercury resistant bacteria can be used. Bacillus sp is a gram-positive bacteria that is resistant to mercury. Besides having the mer operon genes that can transform Hg2+ to Hg0 that is less toxic, Bacillus sp bacteria also produce esterase that cause these bacteria resistant to erythromycin antibiotic. Erythromycin is a macrolide class of antibiotic used for the treatment of diseases caused by Gram-positive bacteria, especially Staphylococcus and Diphtheroids. To determine the resistance of Bacillus sp bacteria against mercury and erythromycin antibiotic. This study used a descriptive exploratory method with samples of bacteria and mercury are already available in the Laboratory of Pharmaceutical Microbiology. Based on the research that has been conducted, showed that the Bacillus sp bacteria is resistant to mercury and erythromycin.Keywords: bacteria, bacillus sp, resistant, mercury, erythromycinAbstrak: Merkuri merupakan logam berat bersifat toksik yang digunakan untuk penambalan gigi dalam bentuk amalgam. Untuk mengurangi efek toksik yang dihasilkan oleh merkuri, dapat digunakan bakteri resisten merkuri. Bakteri Bacillus sp merupakan bakteri gram positif yang resisten terhadap merkuri. Selain memiliki gen mer operon yang dapat mengubah Hg2+ menjadi Hg0 yang kurang toksik, bakteri Bacillus sp juga membentuk esterase yang menyebabkan terjadinya resisten bakteri ini terhadap antibiotik eritromisin. Eritromisin adalah antibiotik golongan makrolid yang digunakan untuk pengobatan penyakit akibat bakteri Gram positif khususnya Staphylococcus dan Diphtheroids. Untuk mengetahui resistensi bakteri Bacillus sp terhadap merkuri dan antibiotik eritromisin. Penelitian ini menggunakan metode deskriptif eksploratif dengan sampel bakteri dan merkuri yang sudah tersedia di Laboratorium Mikrobiologi Farmasi. Berdasarkan hasil penelitian yang telah dilakukan, diperoleh bahwa bakteri Bacillus sp resisten terhadap merkuri dan eritromisin.Kata Kunci: bakteri, bacillus sp, resisten, merkuri, eritromisin

scholarly journals Synthesis, Structure Elucidation, Antibacterial Activities, and Synergistic Effects of Novel Juglone and Naphthazarin Derivatives Against Clinical Methicillin-Resistant Staphylococcus aureus Strains

2021 ◽  
Vol 9 ◽  
Author(s):  
Valentin Duvauchelle ◽  
Chaimae Majdi ◽  
David Bénimélis ◽  
Catherine Dunyach-Remy ◽  
Patrick Meffre ◽  
...  
Keyword(s):  
Synergistic Effects ◽  
Antibacterial Properties ◽  
Clinical Importance ◽  
Antibacterial Activities ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Global Public Health ◽  
Gram Positive ◽  
Drug Resistant Bacteria ◽  
Mrsa Strains

Infections caused by drug-resistant bacteria are a serious threat to human and global public health. Moreover, in recent years, very few antibiotics have been discovered and developed by pharmaceutical companies. Therefore, there is an urgent need to discover and develop new antibacterial agents to combat multidrug-resistant bacteria. In this study, two novel series of juglone/naphthazarin derivatives (43 compounds) were synthesized and evaluated for their antibacterial properties against various clinical and reference Gram-positive MSSA, clinical Gram-positive MRSA, and clinical and reference Gram-negative bacteria E. coli and P. aeruginosa. These strains are of clinical importance because they belong to ESKAPE pathogens. Compounds 3al, 5ag, and 3bg showed promising activity against clinical and reference MSSA (MIC: 1–8 µg/ml) and good efficacy against clinical MRSA (MIC: 2–8 µg/ml) strains. 5am and 3bm demonstrated better activity on both MSSA (MIC: 0.5 µg/ml) and MRSA (MIC: 2 µg/ml) strains. Their MICs were similar to those of cloxacillin against clinical MRSA strains. The synergistic effects of active compounds 3al, 5ag, 5am, 3bg, and 3bm were evaluated with reference antibiotics, and it was found that the antibiotic combination with 3bm efficiently enhanced the antimicrobial activity. Compound 3bm was found to restore the sensitivity of clinical MRSA to cloxacillin and enhanced the antibacterial activity of vancomycin when they were added together. In the presence of 3bm, the MIC values of vancomycin and cloxacillin were lowered up to 1/16th of the original MIC with an FIC index of 0.313. Moreover, compounds 3al, 5ag, 5am, 3bg, and 3bm did not present hemolytic activity on sheep red blood cells. In silico prediction of ADME profile parameter results for 3bm is promising and encouraging for further development.

Venom of Viperidae: A perspective of its antibacterial and antitumor potential

2021 ◽  
Vol 22 ◽  
Author(s):  
André Silva ◽  
Fernando Gonçalves ◽  
Helena Oliveira ◽  
Sérgio Marques
Keyword(s):  
Therapeutic Potential ◽  
Modern Medicine ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Cytotoxic Effects ◽  
Venomous Snake ◽  
Drug Resistant Bacteria ◽  
Antitumor Potential ◽  
Biological Compounds ◽  
Considerable Damage

: The emergence of multi-drug resistant bacteria and limitations on cancer treatment represent two important challenges in modern medicine. Biological compounds have been explored with particular focus on venoms. Although they can be lethal or cause considerable damage to humans, venom is also a source rich in components with high therapeutic potential. Viperidae family is one of the most emblematic venomous snake families and several studies highlighted the antibacterial and antitumor potential of viper toxins. According to the literature, these activities are mainly associated to five protein families – svLAAO, Disintegrins, PLA2, SVMPs and C-type lectins- that act through different mechanisms leading to the inhibition of the growth of bacteria, as well as, cytotoxic effects and inhibition of metastasis process. In this review we provide an overview of the venom toxins produced by species belonging to the Viperidae family, exploring their roles during the envenoming and their pharmacological properties, in order to demonstrate its antibacterial and antitumor potential.

scholarly journals Sarconesin II, a New Antimicrobial Peptide Isolated from Sarconesiopsis magellanica Excretions and Secretions

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2077 ◽  
Author(s):  
Andrea Díaz-Roa ◽  
Abraham Espinoza-Culupú ◽  
Orlando Torres-García ◽  
Monamaris M. Borges ◽  
Ivan N. Avino ◽  
...  
Keyword(s):  
Micrococcus Luteus ◽  
Multidrug Resistant ◽  
Peptide Sequence ◽  
Resistant Bacteria ◽  
Gram Positive ◽  
Antimicrobial Drugs ◽  
Gram Negative ◽  
Gram Positive Bacteria ◽  
Conserved Domain ◽  
Health Institutions

Antibiotic resistance is at dangerous levels and increasing worldwide. The search for new antimicrobial drugs to counteract this problem is a priority for health institutions and organizations, both globally and in individual countries. Sarconesiopsis magellanica blowfly larval excretions and secretions (ES) are an important source for isolating antimicrobial peptides (AMPs). This study aims to identify and characterize a new S. magellanica AMP. RP-HPLC was used to fractionate ES, using C18 columns, and their antimicrobial activity was evaluated. The peptide sequence of the fraction collected at 43.7 min was determined by mass spectrometry (MS). Fluorescence and electronic microscopy were used to evaluate the mechanism of action. Toxicity was tested on HeLa cells and human erythrocytes; physicochemical properties were evaluated. The molecule in the ES was characterized as sarconesin II and it showed activity against Gram-negative (Escherichia coli MG1655, Pseudomonas aeruginosa ATCC 27853, P. aeruginosa PA14) and Gram-positive (Staphylococcus aureus ATCC 29213, Micrococcus luteus A270) bacteria. The lowest minimum inhibitory concentration obtained was 1.9 μM for M. luteus A270; the AMP had no toxicity in any cells tested here and its action in bacterial membrane and DNA was confirmed. Sarconesin II was documented as a conserved domain of the ATP synthase protein belonging to the Fli-1 superfamily. The data reported here indicated that peptides could be alternative therapeutic candidates for use in infections against Gram-negative and Gram-positive bacteria and eventually as a new resource of compounds for combating multidrug-resistant bacteria.

BIOBOARD

2018 ◽  
Vol 22 (04) ◽  
pp. 49-56
Keyword(s):  
Resistance Mechanism ◽  
Drug Carriers ◽  
Resistant Bacteria ◽  
Antibiotics Resistance ◽  
Drug Resistant ◽  
Chiral Molecules ◽  
Liver Cancer Cells ◽  
Drug Resistant Bacteria ◽  
New Findings ◽  
New Antibiotics

ASIA – Natural products identified as potential new antibiotic against various drug-resistant bacteria. ASIA – HKUST discovers new antibiotics resistance mechanism. ASIA – Green tea-based drug carriers improve cancer treatment. ASIA – New molecule can kill five types of deadly drug-resistant superbugs. ASIA – Scientists grow liver cancer cells in lab. ASIA – New findings reveal sex-based and age-based differences in how the gut microbiome affects brain immunity. ASIA – HKUST scientists find new way to produce chiral molecules.

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