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Antibiotics
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Phytocompounds with Antimicrobial Activity: From Discovery to Application
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Phytocompounds with Antimicrobial Activity: From Discovery to Application

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Plant-Derived Antibiotics".

Deadline for manuscript submissions: closed (15 September 2022) | Viewed by 21658

Special Issue Editors

Dr. Roberta Colicchio

E-Mail Website
Guest Editor
Department of Molecular Medicine and Medical Biotechnology, University of Napoli Federico II, Via S. Pansini 5, 80131 Naples, Italy
Interests: antimicrobial activity of natural compounds; animal and cellular models of infection
Special Issues, Collections and Topics in MDPI journals
Dr. Chiara Pagliuca

E-Mail Website
Guest Editor
Department of Molecular Medicine and Medical Biotechnology, University of Napoli Federico II, Via S. Pansini 5, 80131 Naples, Italy
Interests: microbial pathogenesis; microbial molecular biology; gut human microbiota; infections model
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Today, infections associated with multidrug-resistant (MDR) bacteria still represent a great challenge yet to be treated due to limited therapeutic options, thus requiring alternative antimicrobial strategies. In this regard today, a wide range of new drugs are being derived from plant metabolites. Any single plant indeed represents a library of hundreds to thousands of architecturally and stereochemically complex chemicals, termed phytochemicals. Therefore, in recent years, to counteract antimicrobial resistance, phytocompounds with antimicrobial activity are widely recommended by the experts. Their use, in combination with the conventional commercial antibiotics, exhibits superior antimicrobial activities. Moreover, the membrane proteins that were accountable for antibiotic efflux can be effectively treated by antimicrobial phytocompounds that, therefore, could represent new weapons in the battle against intractable infectious diseases. This Special Issue seeks submissions that further our understanding of new, more active phytocompounds with antimicrobial activity focusing on the discovery and development of new molecules and their potential applications.

Dr. Roberta Colicchio
Dr. Chiara Pagliuca
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antibiotics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Phytocompounds
  • Antibacterial activity
  • Multidrug-resistant (MDR) bacteria
  • Modulatory activity
  • Bioactive extracts
  • Synergistic effect

Published Papers (6 papers)

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Research

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12 pages, 3589 KiB  
Article
Synergistic Activity of Tetrandrine and Colistin against mcr-1-Harboring Escherichia coli
by Muhammad Shafiq, Fen Yao, Hazrat Bilal, Sadeeq Ur Rahman, Mi Zeng, Ilyas Ali, Yuebin Zeng, Xin Li, Yumeng Yuan and Xiaoyang Jiao
Antibiotics 2022, 11(10), 1346; https://doi.org/10.3390/antibiotics11101346 - 02 Oct 2022
Cited by 3 | Viewed by 2082
Abstract
Before the emergence of plasmid-mediated colistin resistance, colistin was once considered the last drug of choice for infections caused by carbapenem-resistant bacteria. Currently, researchers are relentlessly exploring possible alternative therapies that could efficiently curb the spread of drug resistance. In this study, we [...] Read more.
Before the emergence of plasmid-mediated colistin resistance, colistin was once considered the last drug of choice for infections caused by carbapenem-resistant bacteria. Currently, researchers are relentlessly exploring possible alternative therapies that could efficiently curb the spread of drug resistance. In this study, we aim to investigate the synergistic antibacterial activity of tetrandrine in combination with colistin against mcr-1-harboring Escherichia coli. We examined the antibacterial activity of tetrandrine in combination with colistin in vivo and in vitro and examined the bacterial cells by fluorescence, scanning, and transmission electron microscopy (TEM) to explore their underlying mechanism of action. We further performed a computational analysis of MCR-1 protein and tetrandrine to determine the interaction interface of these two molecules. We confirmed that neither colistin nor tetrandrine could, on their own, inhibit the growth of mcr-1-positive E. coli. However, in combination, tetrandrine synergistically enhanced colistin activity to inhibit the growth of E. coli both in vivo and in vitro. Similarly, molecular docking showed that tetrandrine interacted with the three crucial amino acids of the MCR-1 protein in the active site, which might inhibit MCR-1 from binding to its substrates, cause MCR-1 to lose its ability to confer resistance. This study confirmed that tetrandrine and colistin have the ability to synergistically overcome the issue of colistin resistance in mcr-1-harboring E. coli. Full article
(This article belongs to the Special Issue Phytocompounds with Antimicrobial Activity: From Discovery to Application)
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10 pages, 1514 KiB  
Article
Icariin in Combination with Amoxycillin-Clavulanate and Ampicillin, but Not Vancomycin, Increases Antibiotic Sensitivity and Growth Inhibition against Methicillin-Resistant Staphylococcus aureus
by María Cardells Peris, Alba Martínez, Marina Pascual Ortíz, Chirag C. Sheth and Veronica Veses
Antibiotics 2022, 11(2), 233; https://doi.org/10.3390/antibiotics11020233 - 11 Feb 2022
Cited by 1 | Viewed by 2179
Abstract
The widespread irrational use of antibiotics in recent years has resulted in an increase in the detection of multi-resistant bacterial strains, particularly methicillin-resistant Staphylococcus aureus (MRSA). The use of natural derivatives such as flavonoids is postulated as one of the most promising avenues [...] Read more.
The widespread irrational use of antibiotics in recent years has resulted in an increase in the detection of multi-resistant bacterial strains, particularly methicillin-resistant Staphylococcus aureus (MRSA). The use of natural derivatives such as flavonoids is postulated as one of the most promising avenues to solve this emerging public health problem. The objective of the present study is to characterize the antimicrobial activity of icariin, a flavonoid compound isolated from a variety of plants of the Epimedium genus, against human and animal clinical MRSA isolates. Our study found that icariin alone did not have any antimicrobial effect on S. aureus or MRSA clinical isolates. However, icariin enhanced the effect of amoxycillin-clavulanate or ampicillin, whereas no effect was seen when used in combination with vancomycin. Specifically, co-incubation of S. aureus with amoxycillin-clavulanate plus icariin resulted in an increased proportion of dead cells, suggesting that this flavonoid potentially increases antimicrobial activity when used in combination with the beta-lactam antibiotic amoxycillin-clavulanate. Furthermore, we demonstrate that co-incubation of S. aureus with AmoxyClav plus icariin resulted in increased membrane disruption and growth inhibition. This study demonstrates the potential utility of icariin in permitting lower antibiotic therapeutic doses in alignment with strategies to reduce the spread of antibiotic resistance. Further research is required to determine the optimum concentration of icariin and to define clinically relevant combinations of flavonoid and antibiotic. Full article
(This article belongs to the Special Issue Phytocompounds with Antimicrobial Activity: From Discovery to Application)
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7 pages, 1347 KiB  
Article
A New Antimicrobial Phenylpropanol from the Leaves of Tabernaemontana inconspicua Stapf. (Apocynaceae) Inhibits Pathogenic Gram-Negative Bacteria
by Lidwine Ngah, Willifred Dongmo Tékapi Tsopgni, Judith Caroline Ngo Nyobe, Alain Tadjong Tcho, Moses K. Langat, Jean Claude Ndom, Eduard Mas-Claret, Nicholas John Sadgrove, Alain François Kamdem Waffo and Methee Phumthum
Antibiotics 2022, 11(1), 121; https://doi.org/10.3390/antibiotics11010121 - 17 Jan 2022
Cited by 1 | Viewed by 2708
Abstract
A chemical investigation of the leaves of Tabernaemontana inconspicua Stapf. led to the isolation of a new phenylpropanol derivative, namely irisdichototin G (1), together with nine known compounds, including one polyol derivative, dambonitol (2); three alkaloids, 10-hydroxycoronaridine (3 [...] Read more.
A chemical investigation of the leaves of Tabernaemontana inconspicua Stapf. led to the isolation of a new phenylpropanol derivative, namely irisdichototin G (1), together with nine known compounds, including one polyol derivative, dambonitol (2); three alkaloids, 10-hydroxycoronaridine (3), voacristine (4) and vobasine (5); two triterpenes lupeol (6), betulinic acid (7) and three sterols, sitosterol (8), sitosterol-3-O-β-D-glucopyranoside (9) and stigmasterol (10). The structure of the new compound, as well as those of the known ones, was established by means of spectroscopic methods: NMR analysis (1H and 13C NMR, 1H-1H-COSY, HSQC, HMBC and NOESY), high-resolution mass spectrometry (HR-ESI-MS) and comparisons with previously reported data. Among the known compounds, compound 2 was firstly reported from the family Apocynaceae. Compounds 1–5 were tested for their antimicrobial effects against three Gram-negative organisms associated with human wound and systemic infections, namely Haemophilus influenzae 9435337A, Klebsiella pneumoniae 17102005 and Pseudomonas aeruginosa 2137659B. Compounds 1, 3, and 5 showed significant antimicrobial effects with minimum inhibitory concentrations (MIC) of 62.5 μg/mL, 62.5 μg/mL and 7.81 μg/mL, respectively, against Haemophilus influenzae, whereas compounds 1 and 5 showed significant antimicrobial effects, with a MIC value of 31.25 μg/mL against Pseudomonas aeruginosa. In addition, compound 3 showed significant antimicrobial activity, with a MIC value of 31.25 μg/mL against Klebsiella pneumoniae. Full article
(This article belongs to the Special Issue Phytocompounds with Antimicrobial Activity: From Discovery to Application)
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23 pages, 43389 KiB  
Article
In Vitro and In Silico Approaches for the Evaluation of Antimicrobial Activity, Time-Kill Kinetics, and Anti-Biofilm Potential of Thymoquinone (2-Methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione) against Selected Human Pathogens
by Kamal A. Qureshi, Mahrukh Imtiaz, Adil Parvez, Pankaj K. Rai, Mariusz Jaremko, Abdul-Hamid Emwas, Avinash D. Bholay and Muhammad Qaiser Fatmi
Antibiotics 2022, 11(1), 79; https://doi.org/10.3390/antibiotics11010079 - 10 Jan 2022
Cited by 18 | Viewed by 5067
Abstract
Thymoquinone (2-methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione; TQ), a principal bioactive phytoconstituent of Nigella sativa essential oil, has been reported to have high antimicrobial potential. Thus, the current study evaluated TQ’s antimicrobial potential against a range of selected human pathogens using in vitro assays, including time-kill kinetics and [...] Read more.
Thymoquinone (2-methyl-5-propan-2-ylcyclohexa-2,5-diene-1,4-dione; TQ), a principal bioactive phytoconstituent of Nigella sativa essential oil, has been reported to have high antimicrobial potential. Thus, the current study evaluated TQ’s antimicrobial potential against a range of selected human pathogens using in vitro assays, including time-kill kinetics and anti-biofilm activity. In silico molecular docking of TQ against several antimicrobial target proteins and a detailed intermolecular interaction analysis was performed, including binding energies and docking feasibility. Of the tested bacteria and fungi, S. epidermidis ATCC 12228 and Candida albicans ATCC 10231 were the most susceptible to TQ, with 50.3 ± 0.3 mm and 21.1 ± 0.1 mm zones of inhibition, respectively. Minimum inhibitory concentration (MIC) values of TQ are in the range of 12.5–50 µg/mL, while minimum biocidal concentration (MBC) values are in the range of 25–100 µg/mL against the tested organisms. Time-kill kinetics of TQ revealed that the killing time for the tested bacteria is in the range of 1–6 h with the MBC of TQ. Anti-biofilm activity results demonstrate that the minimum biofilm inhibitory concentration (MBIC) values of TQ are in the range of 25–50 µg/mL, while the minimum biofilm eradication concentration (MBEC) values are in the range of 25–100 µg/mL, for the tested bacteria. In silico molecular docking studies revealed four preferred antibacterial and antifungal target proteins for TQ: D-alanyl-D-alanine synthetase (Ddl) from Thermus thermophilus, transcriptional regulator qacR from Staphylococcus aureus, N-myristoyltransferase from Candida albicans, and NADPH-dependent D-xylose reductase from Candida tenuis. In contrast, the nitroreductase family protein from Bacillus cereus and spore coat polysaccharide biosynthesis protein from Bacillus subtilis and UDP-N-acetylglucosamine pyrophosphorylase from Aspergillus fumigatus are the least preferred antibacterial and antifungal target proteins for TQ, respectively. Molecular dynamics (MD) simulations revealed that TQ could bind to all four target proteins, with Ddl and NADPH-dependent D-xylose reductase being the most efficient. Our findings corroborate TQ’s high antimicrobial potential, suggesting it may be a promising drug candidate for multi-drug resistant (MDR) pathogens, notably Gram-positive bacteria and Candida albicans. Full article
(This article belongs to the Special Issue Phytocompounds with Antimicrobial Activity: From Discovery to Application)
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Review

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24 pages, 5491 KiB  
Review
Phytocompounds as an Alternative Antimicrobial Approach in Aquaculture
by Naqiuddin Nik Mohamad Nek Rahimi, Ikhsan Natrah, Jiun-Yan Loh, Francis Kumar Ervin Ranzil, Madi Gina, Swee-Hua Erin Lim, Kok-Song Lai and Chou-Min Chong
Antibiotics 2022, 11(4), 469; https://doi.org/10.3390/antibiotics11040469 - 31 Mar 2022
Cited by 16 | Viewed by 4482
Abstract
Despite culturing the fastest-growing animal in animal husbandry, fish farmers are often adversely economically affected by pathogenic disease outbreaks across the world. Although there are available solutions such as the application of antibiotics to mitigate this phenomenon, the excessive and injudicious use of [...] Read more.
Despite culturing the fastest-growing animal in animal husbandry, fish farmers are often adversely economically affected by pathogenic disease outbreaks across the world. Although there are available solutions such as the application of antibiotics to mitigate this phenomenon, the excessive and injudicious use of antibiotics has brought with it major concerns to the community at large, mainly due to the rapid development of resistant bacteria. At present, the use of natural compounds such as phytocompounds that can be an alternative to antibiotics is being explored to address the issue of antimicrobial resistance (AMR). These phytocompounds are bioactive agents that can be found in many species of plants and hold much potential. In this review, we will discuss phytocompounds extracted from plants that have been evidenced to contain antimicrobial, antifungal, antiviral and antiparasitic activities. Further, it has also been found that compounds such as terpenes, phenolics, saponins and alkaloids can be beneficial to the aquaculture industry when applied. This review will focus mainly on compounds that have been identified between 2000 and 2021. It is hoped this review will shed light on promising phytocompounds that can potentially and effectively mitigate AMR. Full article
(This article belongs to the Special Issue Phytocompounds with Antimicrobial Activity: From Discovery to Application)
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22 pages, 1896 KiB  
Review
Phytocompound Mediated Blockage of Quorum Sensing Cascade in ESKAPE Pathogens
by Sreejita Ghosh, Dibyajit Lahiri, Moupriya Nag, Ankita Dey, Soumya Pandit, Tanmay Sarkar, Siddhartha Pati, Zulhisyam Abdul Kari, Ahmad Razali Ishak, Hisham Atan Edinur and Rina Rani Ray
Antibiotics 2022, 11(1), 61; https://doi.org/10.3390/antibiotics11010061 - 05 Jan 2022
Cited by 21 | Viewed by 3494
Abstract
Increased resistance of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp. (ESKAPE) pathogens against various drugs has enhanced the urge for the development of alternate therapeutics. Quorum sensing (QS) is a density dependent [...] Read more.
Increased resistance of Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter sp. (ESKAPE) pathogens against various drugs has enhanced the urge for the development of alternate therapeutics. Quorum sensing (QS) is a density dependent cell-to-cell communication mechanism responsible for controlling pathogenicity with the regulation of gene expression. Thus, QS is considered a potential target for the development of newer anti-biofilm agents that do not depend on the utilization of antibiotics. Compounds with anti-QS effects are known as QS inhibitors (QSIs), and they can inhibit the QS mechanism that forms the major form in the development of bacterial pathogenesis. A diverse array of natural compounds provides a plethora of anti-QS effects. Over recent years, these natural compounds have gained importance as new strategies for combating the ESKAPE pathogens and inhibiting the genes involved in QS. Different pharmacognostical and pharmacological studies have been carried out so far for identification of novel drugs or for the discovery of their unique structures that may help in developing more effective anti-biofilm therapies. The main objective of this review is to discuss the various natural compounds, so far identified and their employed mechanisms in hindering the genes responsible for QS leading to bacterial pathogenesis. Full article
(This article belongs to the Special Issue Phytocompounds with Antimicrobial Activity: From Discovery to Application)
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