Research

Jump to: Review

21 pages, 3907 KiB

Open AccessArticle

A Novel Antimicrobial Mechanism of Azalomycin F Acting on Lipoteichoic Acid Synthase and Cell Envelope

by Zilong Luo, Pingyi Li, Duoduo Zhang, Jianping Zhu, Wan Wang, Wenjia Zhao, Peibo Li and Ganjun Yuan

Molecules 2024, 29(4), 856; https://doi.org/10.3390/molecules29040856 - 14 Feb 2024

Viewed by 654

Abstract

Lipoteichoic acid (LTA) plays an essential role in bacterial growth and resistance to antibiotics, and LTA synthetase (LtaS) was considered as an attractive target for combating Gram-positive infections. Azalomycin F, a natural guanidyl-containing polyhydroxy macrolide, can target the LTA of Staphylococcus aureus. [...] Read more.

Lipoteichoic acid (LTA) plays an essential role in bacterial growth and resistance to antibiotics, and LTA synthetase (LtaS) was considered as an attractive target for combating Gram-positive infections. Azalomycin F, a natural guanidyl-containing polyhydroxy macrolide, can target the LTA of Staphylococcus aureus. Using various technologies including enzyme-linked immunosorbent assay, transmission electron microscope, proteomics, and parallel reaction monitoring, here, the experimental results indicated that azalomycin F can accelerate the LTA release and disrupt the cell envelope, which would also lead to the feedback upregulation on the expressions of LtaS and other related enzymes. Simultaneously, the reconstituted enzyme activity evaluations showed that azalomycin F can significantly inhibit the extracellular catalytic domain of LtaS (eLtaS), while this was vague for LtaS embedded in the liposomes. Subsequently, the fluorescence analyses for five incubation systems containing azalomycin F and eLtaS or the LtaS-embedded liposome indicated that azalomcyin F can spontaneously bind to the active center of LtaS. Combining the mass spectroscopy analyses and the molecular dockings, the results further indicated that this interaction involves the binding sites of substrates and the LTA prolongation, especially the residues Lys299, Phe353, Trp354 and His416. All these suggested that azalomycin F has multiple antibacterial mechanisms against S. aureus. It can not only inhibit LTA biosynthesis through the interactions of its guanidyl side chain with the active center of LtaS but also disrupt the cell envelope through the synergistic effect of accelerating the LTA release, damaging the cell membrane, and electrostatically interacting with LTA. Simultaneously, these antibacterial mechanisms exhibit a synergistic inhibition effect on S. aureus cells, which would eventually cause the cellular autolysis. Full article

(This article belongs to the Special Issue Natural Products as Antimicrobial Agents: From Extraction to Therapeutic Applications)

► Show Figures

Figure 1

19 pages, 3334 KiB

Open AccessArticle

Natural Products from Singapore Soil-Derived Streptomycetaceae Family and Evaluation of Their Biological Activities

by Elaine-Jinfeng Chin, Kuan-Chieh Ching, Zann Y. Tan, Mario Wibowo, Chung-Yan Leong, Lay-Kien Yang, Veronica W. P. Ng, Deborah C. S. Seow, Yoganathan Kanagasundaram and Siew-Bee Ng

Molecules 2023, 28(15), 5832; https://doi.org/10.3390/molecules28155832 - 02 Aug 2023

Cited by 1 | Viewed by 1015

Abstract

Natural products have long been used as a source of antimicrobial agents against various microorganisms. Actinobacteria are a group of bacteria best known to produce a wide variety of bioactive secondary metabolites, including many antimicrobial agents. In this study, four actinobacterial strains found [...] Read more.

Natural products have long been used as a source of antimicrobial agents against various microorganisms. Actinobacteria are a group of bacteria best known to produce a wide variety of bioactive secondary metabolites, including many antimicrobial agents. In this study, four actinobacterial strains found in Singapore terrestrial soil were investigated as potential sources of new antimicrobial compounds. Large-scale cultivation, chemical, and biological investigation led to the isolation of a previously undescribed tetronomycin A (1) that demonstrated inhibitory activities against both Gram-positive bacteria Staphylococcus aureus (SA) and methicillin-resistant Staphylococcus aureus (MRSA) (i.e., MIC₉₀ of 2–4 μM and MBC₉₀ of 9–12 μM), and several known antimicrobial compounds, namely nonactin, monactin, dinactin, 4E-deacetylchromomycin A3, chromomycin A2, soyasaponin II, lysolipin I, tetronomycin, and naphthomevalin. Tetronomycin showed a two- to six-fold increase in antibacterial activity (i.e., MIC₉₀ and MBC₉₀ of 1–2 μM) as compared to tetronomycin A (1), indicating the presence of an oxy-methyl group at the C-27 position is important for antibacterial activity. Full article

(This article belongs to the Special Issue Natural Products as Antimicrobial Agents: From Extraction to Therapeutic Applications)

► Show Figures

Figure 1

20 pages, 3230 KiB

Open AccessArticle

Luteolin Isolated from Juncus acutus L., a Potential Remedy for Human Coronavirus 229E

by Asma Hakem, Lowiese Desmarets, Ramla Sahli, Rawen Ben Malek, Charline Camuzet, Nathan François, Gabriel Lefèvre, Jennifer Samaillie, Sophie Moureu, Sevser Sahpaz, Sandrine Belouzard, Riadh Ksouri, Karin Séron and Céline Rivière

Molecules 2023, 28(11), 4263; https://doi.org/10.3390/molecules28114263 - 23 May 2023

Cited by 3 | Viewed by 1549

Abstract

The COVID-19 pandemic, caused by SARS-CoV-2, addressed the lack of specific antiviral drugs against coronaviruses. In this study, bioguided fractionation performed on both ethyl acetate and aqueous sub-extracts of Juncus acutus stems led to identifying luteolin as a highly active antiviral molecule against [...] Read more.

The COVID-19 pandemic, caused by SARS-CoV-2, addressed the lack of specific antiviral drugs against coronaviruses. In this study, bioguided fractionation performed on both ethyl acetate and aqueous sub-extracts of Juncus acutus stems led to identifying luteolin as a highly active antiviral molecule against human coronavirus HCoV-229E. The apolar sub-extract (CH₂Cl₂) containing phenanthrene derivatives did not show antiviral activity against this coronavirus. Infection tests on Huh-7 cells, expressing or not the cellular protease TMPRSS2, using luciferase reporter virus HCoV-229E-Luc showed that luteolin exhibited a dose-dependent inhibition of infection. Respective IC₅₀ values of 1.77 µM and 1.95 µM were determined. Under its glycosylated form (luteolin-7-O-glucoside), luteolin was inactive against HCoV-229E. Time of addition assay showed that utmost anti-HCoV-229E activity of luteolin was achieved when added at the post-inoculation step, indicating that luteolin acts as an inhibitor of the replication step of HCoV-229E. Unfortunately, no obvious antiviral activity for luteolin was found against SARS-CoV-2 and MERS-CoV in this study. In conclusion, luteolin isolated from Juncus acutus is a new inhibitor of alphacoronavirus HCoV-229E. Full article

(This article belongs to the Special Issue Natural Products as Antimicrobial Agents: From Extraction to Therapeutic Applications)

► Show Figures

Figure 1

21 pages, 42496 KiB

Open AccessArticle

Immunomodulatory Efficacy-Mediated Anti-HCV and Anti-HBV Potential of Kefir Grains; Unveiling the In Vitro Antibacterial, Antifungal, and Wound Healing Activities

by Sawsan Abd Ellatif, Elsayed S. Abdel Razik, Marwa M. Abu-Serie, Ahmed Mahfouz, Abdullah F. Shater, Fayez M. Saleh, Mohamed M. Hassan, Walaa F. Alsanie, Abdullah Altalhi, Ghadir E. Daigham and Amira Y. Mahfouz

Molecules 2022, 27(6), 2016; https://doi.org/10.3390/molecules27062016 - 21 Mar 2022

Cited by 5 | Viewed by 3280

Abstract

The utilization of fermented foods with health-promoting properties is becoming more popular around the world. Consequently, kefir, a fermented milk beverage made from kefir grains, was shown in numerous studies to be a probiotic product providing significant health benefits. Herein, we assessed the [...] Read more.

The utilization of fermented foods with health-promoting properties is becoming more popular around the world. Consequently, kefir, a fermented milk beverage made from kefir grains, was shown in numerous studies to be a probiotic product providing significant health benefits. Herein, we assessed the antibacterial and antifungal potential of kefir against a variety of pathogenic bacteria and fungi. This study also showed the effectiveness of kefir in healing wounds in human gastric epithelial cells (GES-1) by (80.78%) compared with control (55.75%) within 48 h. The quantitative polymerase chain reaction (qPCR) results of kefir-treated HCV- or HBV- infected cells found that 200 µg/mL of kefir can eliminate 92.36% of HCV and 75.71% of HBV relative to the untreated infected cells, whereas 800 µg/mL (the highest concentration) completely eradicated HCV and HBV. Moreover, the estimated IC₅₀ values of kefir, at which HCV and HBV were eradicated by 50%, were 63.84 ± 5.81 µg/mL and 224.02 ± 14.36 µg/mL, correspondingly. Kefir can significantly suppress the elevation of TNF-α and upregulate IL-10 and INF-γ in both treated HCV- and HBV-infected cells. High-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analysis of kefir revealed the presence of numerous active metabolites which mainly contribute to the antimicrobial, antiviral, and immunomodulatory activities. This study demonstrated, for the first time, the anti-HBV efficacy of kefir while also illustrating the immunomodulatory impact in the treated HBV-infected cells. Accordingly, kefir represents a potent antiviral agent against both viral hepatitis C and B, as well as having antimicrobial and wound healing potential. Full article

(This article belongs to the Special Issue Natural Products as Antimicrobial Agents: From Extraction to Therapeutic Applications)

► Show Figures

Figure 1

13 pages, 930 KiB

Open AccessArticle

A Validated HPLC-PDA-HRMS Method to Investigate the Biological Stability and Metabolism of Antiparasitic Triterpenic Esters

by Laura Schioppa, Fanta Fall, Sergio Ortiz, Jacques H. Poupaert and Joelle Quetin-Leclercq

Molecules 2021, 26(23), 7154; https://doi.org/10.3390/molecules26237154 - 26 Nov 2021

Viewed by 1599

Abstract

Pentacyclic triterpenes (PTs) are commonly found in medicinal plants with well-known antiparasitic effects. Previous research on C-3 and C-27 triterpenic esters showed effective and selective in vitro antiparasitic activities and in vivo effectiveness by parenteral routes. The aim of this study was to [...] Read more.

Pentacyclic triterpenes (PTs) are commonly found in medicinal plants with well-known antiparasitic effects. Previous research on C-3 and C-27 triterpenic esters showed effective and selective in vitro antiparasitic activities and in vivo effectiveness by parenteral routes. The aim of this study was to determine triterpenic esters’ stability in different biological-like media and the main microsomal degradation products. An HPLC-PDA method was developed and validated to simultaneously analyze and quantify bioactive triterpenic esters in methanol (LOQ: 2.5 and 1.25–100 µg/mL) and plasma (LOQ: 5–125 µg/mL). Overall, both triterpenic esters showed a stable profile in aqueous and buffered solutions as well as in entire plasma, suggesting gaining access to the ester function is difficult for plasma enzymes. Conversely, after 1 h, 30% esters degradation in acidic media was observed with potential different hydrolysis mechanisms. C-3 (15 and 150 µM) and C-27 esters (150 µM) showed a relatively low hepatic microsomal metabolism (<23%) after 1 h, which was significantly higher in the lowest concentration of C-27 esters (15 µM) (>40% degradation). Metabolic HPLC-PDA-HRMS studies suggested hydrolysis, hydroxylation, dehydration, O-methylation, hydroxylation and/or the reduction of hydrolyzed derivatives, depending on the concentration and the position of the ester link. Further permeability and absorption studies are required to better define triterpenic esters pharmacokinetic and specific formulations designed to increase their oral bioavailability. Full article

(This article belongs to the Special Issue Natural Products as Antimicrobial Agents: From Extraction to Therapeutic Applications)

► Show Figures

Graphical abstract

17 pages, 2730 KiB

Open AccessArticle

Inhibition of Bacterial Efflux Pumps by Crude Extracts and Essential Oil from Myristica fragrans Houtt. (Nutmeg) Seeds against Methicillin-Resistant Staphylococcus aureus

by Thidar Oo, Bhanubong Saiboonjan, Sukanya Srijampa, Arpasiri Srisrattakarn, Khaetthareeya Sutthanut, Ratree Tavichakorntrakool, Aroonwadee Chanawong, Aroonlug Lulitanond and Patcharaporn Tippayawat

Molecules 2021, 26(15), 4662; https://doi.org/10.3390/molecules26154662 - 31 Jul 2021

Cited by 14 | Viewed by 3221

Abstract

Myristicafragrans Houtt. (Nutmeg) is a widely known folk medicine across several parts of Asia, particularly used in antimicrobial treatment. Bacterial resistance involves the expression of efflux pump systems (chromosomal norA and mepA) in methicillin-resistant Staphylococcus aureus (MRSA). Crude extract (CE) [...] Read more.

Myristicafragrans Houtt. (Nutmeg) is a widely known folk medicine across several parts of Asia, particularly used in antimicrobial treatment. Bacterial resistance involves the expression of efflux pump systems (chromosomal norA and mepA) in methicillin-resistant Staphylococcus aureus (MRSA). Crude extract (CE) and essential oil (EO) obtained from nutmeg were applied as efflux pump inhibitors (EPIs), thereby enhancing the antimicrobial activity of the drugs they were used in. The major substances in CE and EO, which function as EPIs, in a descending order of % peak area include elemicin, myristicin, methoxyeugenol, myristicin, and asarone. Here, we investigated whether the low amount of CE and EO used as EPIs was sufficient to sensitize MRSA killing using the antibiotic ciprofloxacin, which acts as an efflux system. Interestingly, synergy between ciprofloxacin and CE or EO revealed the most significant viability of MRSA, depending on norA and mepA, the latter being responsible for EPI function of EO. Therefore, CE and EO obtained from nutmeg can act as EPIs in combination with substances that act as efflux systems, thereby ensuring that the MRSA strain is susceptible to antibiotic treatment. Full article

(This article belongs to the Special Issue Natural Products as Antimicrobial Agents: From Extraction to Therapeutic Applications)

► Show Figures

Graphical abstract

Review

Jump to: Research

22 pages, 20000 KiB

Open AccessReview

Biodiversity of Secondary Metabolites Compounds Isolated from Phylum Actinobacteria and Its Therapeutic Applications

by Muhanna Mohammed Al-shaibani, Radin Maya Saphira Radin Mohamed, Nik Marzuki Sidik, Hesham Ali El Enshasy, Adel Al-Gheethi, Efaq Noman, Nabil Ali Al-Mekhlafi and Noraziah Mohamad Zin

Molecules 2021, 26(15), 4504; https://doi.org/10.3390/molecules26154504 - 26 Jul 2021

Cited by 32 | Viewed by 6986

Abstract

The current review aims to summarise the biodiversity and biosynthesis of novel secondary metabolites compounds, of the phylum Actinobacteria and the diverse range of secondary metabolites produced that vary depending on its ecological environments they inhabit. Actinobacteria creates a wide range of bioactive [...] Read more.

The current review aims to summarise the biodiversity and biosynthesis of novel secondary metabolites compounds, of the phylum Actinobacteria and the diverse range of secondary metabolites produced that vary depending on its ecological environments they inhabit. Actinobacteria creates a wide range of bioactive substances that can be of great value to public health and the pharmaceutical industry. The literature analysis process for this review was conducted using the VOSviewer software tool to visualise the bibliometric networks of the most relevant databases from the Scopus database in the period between 2010 and 22 March 2021. Screening and exploring the available literature relating to the extreme environments and ecosystems that Actinobacteria inhabit aims to identify new strains of this major microorganism class, producing unique novel bioactive compounds. The knowledge gained from these studies is intended to encourage scientists in the natural product discovery field to identify and characterise novel strains containing various bioactive gene clusters with potential clinical applications. It is evident that Actinobacteria adapted to survive in extreme environments represent an important source of a wide range of bioactive compounds. Actinobacteria have a large number of secondary metabolite biosynthetic gene clusters. They can synthesise thousands of subordinate metabolites with different biological actions such as anti-bacterial, anti-parasitic, anti-fungal, anti-virus, anti-cancer and growth-promoting compounds. These are highly significant economically due to their potential applications in the food, nutrition and health industries and thus support our communities’ well-being. Full article

(This article belongs to the Special Issue Natural Products as Antimicrobial Agents: From Extraction to Therapeutic Applications)

► Show Figures

Graphical abstract

23 pages, 6411 KiB

Open AccessReview

Promising Antimicrobial Properties of Bioactive Compounds from Different Honeybee Products

by Magdalena Ratajczak, Dorota Kaminska, Eliza Matuszewska, Elżbieta Hołderna-Kedzia, Jarosław Rogacki and Jan Matysiak

Molecules 2021, 26(13), 4007; https://doi.org/10.3390/molecules26134007 - 30 Jun 2021

Cited by 16 | Viewed by 4324

Abstract

Bee products have been known for centuries for their versatile healing properties. In recent decades they have become the subject of documented scientific research. This review aims to present and compare the impact of bee products and their components as antimicrobial agents. Honey, [...] Read more.

Bee products have been known for centuries for their versatile healing properties. In recent decades they have become the subject of documented scientific research. This review aims to present and compare the impact of bee products and their components as antimicrobial agents. Honey, propolis, royal jelly and bee venom are bee products that have antibacterial properties. Sensitivity of bacteria to these products varies considerably between products and varieties of the same product depending on their origin. According to the type of bee product, different degrees of activity were observed against Gram-positive and Gram-negative bacteria, yeasts, molds and dermatophytes, as well as biofilm-forming microorganisms. Pseudomonas aeruginosa turned out to be the most resistant to bee products. An analysis of average minimum inhibitory concentration values for bee products showed that bee venom has the strongest bacterial effectiveness, while royal jelly showed the weakest antibacterial activity. The most challenging problems associated with using bee products for medical purposes are dosage and safety. The complexity and variability in composition of these products raise the need for their standardization before safe and predictable clinical uses can be achieved. Full article

(This article belongs to the Special Issue Natural Products as Antimicrobial Agents: From Extraction to Therapeutic Applications)

► Show Figures

Figure 1

Journal Menu

Journal Browser

Natural Products as Antimicrobial Agents: From Extraction to Therapeutic Applications

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (8 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI