Natural Compounds as Antimicrobial Agents

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Novel Antimicrobial Agents".

Deadline for manuscript submissions: closed (30 November 2019) | Viewed by 105780

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Special Issue Editors

Department of Analytical Chemistry, Nutrition and Bromatology, Faculty of Veterinary Science, University of Santiago de Compostela, 27002 Lugo, Spain
Interests: food safety; analytical chemistry; food microbiology; antimicrobial resistant bacteria; food-borne pathogens; transcriptomics; genotyping; chromatography; mass spectrometry; biofilms; antimicrobial detection; microbiome
Special Issues, Collections and Topics in MDPI journals
Department of Analytical Chemistry, Nutrition and Bromatology, Faculty of Veterinary Science, University of Santiago de Compostela, 27002 Lugo, Spain
Interests: microbiota; micobiota; antimicrobials; nutrition; health; food and feed
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Since the discovery of antibiotics, these compounds have increased in use for the treatment of human and animal infections. In addition, antibiotics have been and are used for other purposes, such as the control of microbiota in animal production, specific disinfection or in several laboratory procedures. At the end of the past century the emergence of a high number of antimicrobial resistances to a high number of “classic” antibiotics led to the progressive ban of these compounds for other purposes than authorized clinical uses by the authorities. This global emergency has revived the research interest in the so-called natural antimicrobials. These natural compounds can be used not only in some clinical procedures, but mainly as additives in processed food, in active films for food packaging, in animal production, or for specific disinfection procedures. The use of these compounds in the food industry can result in a commercial advantage due to the better perception of consumers with respect to these compounds in comparison with industrially-produced substances. Some of these compounds are essential oils or specific compounds directly derived from several plants, fruits and or spices, and even substances of animal origin, such as propolis, lysozyme or chitosan among others, as well as new compounds that are discovered regularly. Today, many of these compounds have not only been rediscovered, but are also the object of new applications, such as micro-encapsulation, nanoparticles, activity against microbial biofilms, and effects on transcriptomics, and have been discovered for new antifungal or antiviral properties. Thus, this Special Issue will cover, but not limited to:

  • new natural antimicrobial compounds
  • antimicrobial effects
  • clinical applications
  • animal production applications
  • antifungal properties
  • antiviral properties
  • food applications
  • new formulations
  • antibacterial mechanisms
  • antifungal mechanisms
  • MICs
  • combination with other antimicrobials
  • global microbiome changes

Despite of the important amount of research that has been carried out on these compounds, the low amount of legal regulation of these substances is leading to a wide number of new applications not previously explored, which we expect will be covered in this issue.

Prof. Dr. Carlos M. Franco
Prof. Dr. Beatriz Vázquez Belda
Guest Editors

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Published Papers (18 papers)

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Editorial

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3 pages, 195 KiB  
Editorial
Natural Compounds as Antimicrobial Agents
by Carlos Manuel Franco and Beatriz I. Vázquez
Antibiotics 2020, 9(5), 217; https://doi.org/10.3390/antibiotics9050217 - 29 Apr 2020
Cited by 14 | Viewed by 3744
Abstract
During the first two decades of this century, conventional antimicrobial compounds have been found out to have more bacterial resistance. What has also been worrying is the rediscovery of the so-called “natural compounds”, which in turn have a good name among the average [...] Read more.
During the first two decades of this century, conventional antimicrobial compounds have been found out to have more bacterial resistance. What has also been worrying is the rediscovery of the so-called “natural compounds”, which in turn have a good name among the average citizen because of the former’s plant or animal origin. However, they do not form a well-classified group of substances. This Special Issue consists of five reviews focusing on clinical bacteria applications in food and their specific effects upon virulent bacterial factors. You will also find a research on much needed, new antimicrobials sourced in extreme environments, and secondary metabolites of Burkholderia. This issue includes 12 original research papers which will provide you with an in-depth coverage of the protein extract activity, as well as the activity of other plant extracts, on fighting bacteria, fungi or diarrhea. Their use in broilers or laying eggs for production purposes has also been focused on in order to improve gut microbiota. Last but not least, we should not forget about honey and its effect; Allium sativum-fermented extracts, as well as other “natural” compounds, have been studied in their fight against biofilms. Furthermore, we have also examined the use of essential oils, which are currently used in edibles such as fresh sausages. The present work also deals with other applications such as natural compound derivatives as well as compound mixtures. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)

Research

Jump to: Editorial, Review

14 pages, 3606 KiB  
Article
The Bactericidal Activity of Protein Extracts from Loranthus europaeus Berries: A Natural Resource of Bioactive Compounds
by Rosa Luisa Ambrosio, Lorena Gratino, Sara Mirino, Ennio Cocca, Antonino Pollio, Aniello Anastasio, Gianna Palmieri, Marco Balestrieri, Angelo Genovese and Marta Gogliettino
Antibiotics 2020, 9(2), 47; https://doi.org/10.3390/antibiotics9020047 - 28 Jan 2020
Cited by 10 | Viewed by 3616
Abstract
Loranthus europaeus is a well-known and important medicinal plant, with a long history of traditional medicine use. Several studies showed that it contains many bioactive compounds with a wide range of pharmacological effects. In light of these past researches, L. europaeus were chosen [...] Read more.
Loranthus europaeus is a well-known and important medicinal plant, with a long history of traditional medicine use. Several studies showed that it contains many bioactive compounds with a wide range of pharmacological effects. In light of these past researches, L. europaeus were chosen to consider its potential antimicrobial action. To this aim, different protocols were performed to selectively extract protein compounds, from L. europaeus yellow fruits, and evaluate the antimicrobial activity against four phytopathogenic fungi (Aspergillus niger, Alternaria spp., Penicillium spp., Botritis cinereus) and a number of foodborne bacterial pathogens (Listeria monocytogenes, Staphylococcus aureus strains, Salmonella Typhimurium and Escherichia coli) by using serial dilutions and colony formation assays. Results evidenced no antifungal activity but a notable bactericidal efficiency of a crude protein extract against two foodborne pathogens, with minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values between 0.2 and 0.5 mg/mL, being S. aureus strains the most susceptible bacteria. Moreover, a strong bactericidal activity against S. aureus M7 was observed by two partially purified protein fractions of about 600 and 60 kDa molecular mass in native conditions. Therefore, these plant protein extracts could be used as natural alternative preventives to control food poisoning diseases and preserve foodstuff avoiding health hazards of chemically antimicrobial applications. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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12 pages, 1711 KiB  
Article
Honey as a Strategy to Fight Candida tropicalis in Mixed-Biofilms with Pseudomonas aeruginosa
by Liliana Fernandes, Ana Oliveira, Mariana Henriques and Maria Elisa Rodrigues
Antibiotics 2020, 9(2), 43; https://doi.org/10.3390/antibiotics9020043 - 21 Jan 2020
Cited by 16 | Viewed by 4549
Abstract
Fungal contaminations with Candida species are commonly responsible for several infections, especially when associated to bacteria. The therapeutic approach commonly used is being compromised due to microbial resistances of these microorganisms to antimicrobial agents, especially in biofilm. The use of honey as an [...] Read more.
Fungal contaminations with Candida species are commonly responsible for several infections, especially when associated to bacteria. The therapeutic approach commonly used is being compromised due to microbial resistances of these microorganisms to antimicrobial agents, especially in biofilm. The use of honey as an antimicrobial agent has been emerging as a valuable solution and proving its potential in planktonic and in biofilm cells. This work aims to assess the effect of different honeys on biofilms of Candida tropicalis and Pseudomonas aeruginosa. The effect of Portuguese heather (PH) and manuka honeys on planktonic growth of Candida was initially evaluated by determination of the minimum inhibitory concentrations (MIC). Then, the same effect was evaluated in mixed biofilms, by colony-forming units numeration and fluorescence microscopy. The combinations of honey plus fluconazole and gentamicin were also tested. The results showed that the honeys tested enabled a great reduction of C. tropicalis, both in planktonic (12.5% and 25% of MIC for PH and manuka) and in biofilm. In polymicrobial biofilms, the use of PH and manuka honeys was revealed to be a promising choice and an alternative treatment, since they were able to reduce cells from both species. No synergistic effect was observed in antimicrobial combinations assays against polymicrobial biofilms. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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9 pages, 251 KiB  
Article
Effects of Dietary Chicory (Chicorium intybus L.) and Probiotic Blend as Natural Feed Additives on Performance Traits, Blood Biochemistry, and Gut Microbiota of Broiler Chickens
by Mohammadreza Khoobani, Seyyed-Hamed Hasheminezhad, Faramin Javandel, Mehran Nosrati, Alireza Seidavi, Isam T. Kadim, Vito Laudadio and Vincenzo Tufarelli
Antibiotics 2020, 9(1), 5; https://doi.org/10.3390/antibiotics9010005 - 20 Dec 2019
Cited by 36 | Viewed by 6110
Abstract
The experiment was designed to determine the effect of different levels of chicory (Chicorium intybus L.) powder and a probiotic blend (PrimaLac®) on productive performance, blood biochemical parameters, and ileal microbiota in broiler chickens. A total of 225 one-day-old broilers [...] Read more.
The experiment was designed to determine the effect of different levels of chicory (Chicorium intybus L.) powder and a probiotic blend (PrimaLac®) on productive performance, blood biochemical parameters, and ileal microbiota in broiler chickens. A total of 225 one-day-old broilers (Ross 308) were used in a completely randomized design with five experimental diets as follows: 1—basal-diet without supplements (control-group); 2—basal-diet including probiotic blend; 3— basal-diet including 0.10% chicory; 4—basal-diet including 0.15% chicory; 5—basal-diet including 0.20% chicory. At 42 days of age, representative birds per replicate were randomly selected for blood samples and carcass measurements. Results showed that the body weight gain of broilers fed the probiotic blend or 0.10% chicory was significantly (P < 0.05) higher than those fed on the other treatments. The abdominal fat pad was significantly (P < 0.05) lower in birds fed diets including chicory compared with control or probiotic. Blood triglycerides and LDL levels were reduced (P < 0.05) and HDL increased (P < 0.05) when fed probiotic or chicory whereas no significant effect on the other serum parameters was found. Broiler ileal microflora from the control group had significantly (P < 0.05) higher count of E. coli and lower Lactobacillus than those from the other groups. From findings, it is possible to conclude that dietary chicory powder supported positively growth performance and improved gut microbiota in broiler chickens. However, more research is needed on this subject to better understand the mode of action of feed additives used. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
13 pages, 775 KiB  
Article
Short Chain Fatty Acids Commonly Produced by Gut Microbiota Influence Salmonella enterica Motility, Biofilm Formation, and Gene Expression
by Alexandre Lamas, Patricia Regal, Beatriz Vázquez, Alberto Cepeda and Carlos Manuel Franco
Antibiotics 2019, 8(4), 265; https://doi.org/10.3390/antibiotics8040265 - 13 Dec 2019
Cited by 57 | Viewed by 6052
Abstract
Short chain fatty acids (SCFAs) are commonly produced by healthy gut microbiota and they have a protective role against enteric pathogens. SCFAs also have direct antimicrobial activity against bacterial pathogens by diffusion across the bacterial membrane and reduction of intracellular pH. Due to [...] Read more.
Short chain fatty acids (SCFAs) are commonly produced by healthy gut microbiota and they have a protective role against enteric pathogens. SCFAs also have direct antimicrobial activity against bacterial pathogens by diffusion across the bacterial membrane and reduction of intracellular pH. Due to this antimicrobial activity, SCFAs have promising applications in human health and food safety. In this study, the minimum inhibitory concentrations (MICs) of four SCFAs (acetic acid, butyric acid, propionic acid, and valeric acid) in Salmonella strains isolated from poultry were determined. The effect of subinhibitory concentrations of SCFAs in Salmonella biofilm formation, motility, and gene expression was also evaluated. Butyric acid, propionic acid, and valeric acid showed a MIC of 3750 µg/mL in all strains tested, while the MIC of acetic acid was between 1875 and 3750 µg/mL. Subinhibitory concentrations of SCFAs significantly (p < 0.05) reduced the motility of all Salmonella strains, especially in the presence of acetic acid. Biofilm formation was also significantly (p < 0.05) lower in the presence of SCFAs in some of the Salmonella strains. Salmonella strain. Salmonella Typhimurium T7 showed significant (p < 0.05) upregulation of important virulence genes, such as invA and hilA, especially in the presence of butyric acid. Therefore, SCFAs are promising substances for the inhibition of the growth of foodborne pathogens. However, it is important to avoid the use of subinhibitory concentrations that could increase the virulence of foodborne pathogen Salmonella. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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12 pages, 997 KiB  
Article
Prevention of Pseudomonas aeruginosa Biofilm Formation on Soft Contact Lenses by Allium sativum Fermented Extract (BGE) and Cannabinol Oil Extract (CBD)
by Valeria Di Onofrio, Renato Gesuele, Angela Maione, Giorgio Liguori, Renato Liguori, Marco Guida, Roberto Nigro and Emilia Galdiero
Antibiotics 2019, 8(4), 258; https://doi.org/10.3390/antibiotics8040258 - 10 Dec 2019
Cited by 21 | Viewed by 5302
Abstract
Two natural mixtures, Allium sativum fermented extract (BGE) and cannabinol oil extract (CBD), were assessed for their ability to inhibit and remove Pseudomonas aeruginosa biofilms on soft contact lenses in comparison to a multipurpose Soft Contact Lens-care solution present on the Italian market. [...] Read more.
Two natural mixtures, Allium sativum fermented extract (BGE) and cannabinol oil extract (CBD), were assessed for their ability to inhibit and remove Pseudomonas aeruginosa biofilms on soft contact lenses in comparison to a multipurpose Soft Contact Lens-care solution present on the Italian market. Pseudomonas aeruginosa (ATCC 9027 strain) and Pseudomonas aeruginosa clinical strains isolated from ocular swabs were tested. Quantification of the biofilm was done using the microtiter plate assay and the fractional inhibitory concentration index was calculated. Both forms of Pseudomonas aeruginosa generated biofilms. BGE at minimal inhibitory concentration (MIC) showed inhibition percentages higher than 55% for both strains, and CBD inhibited biofilm formation by about 70%. The care solution at MIC inhibited biofilm formation by about 50% for both strains tested. The effect of BGE on the eradication of the microbial biofilm on soft contact lenses at MIC was 45% eradication for P. aeruginosa ATCC 9027 and 36% for P. aeruginosa clinical strain. For CBD, we observed 24% biofilm eradication for both strains. For the care solution, the eradication MICs were 43% eradication for P. aeruginosa ATCC 9027 and 41% for P. aeruginosa clinical strain. It was observed that both the test soft contact lenses solution/BGE (fractional inhibitory concentration index: 0.450) and the test soft contact lenses solution/CBD (fractional inhibitory concentration index: 0.153) combinations exhibited synergistic antibiofilm activity against most of the studied bacteria. The study showed that BGE and CBD have good effect on inhibition of biofilm formation and removal of preformed biofilms, which makes them promising agents that could be exploited to develop more effective care solutions. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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12 pages, 1218 KiB  
Article
In-Vitro Inhibition of Staphylococcal Pathogenesis by Witch-Hazel and Green Tea Extracts
by Reuven Rasooly, Adel Molnar, Hwang-Yong Choi, Paula Do, Kenneth Racicot and Emmanouil Apostolidis
Antibiotics 2019, 8(4), 244; https://doi.org/10.3390/antibiotics8040244 - 29 Nov 2019
Cited by 16 | Viewed by 4486
Abstract
whISOBAX (WH), an extract of the witch-hazel plant that is native to the Northeast coast of the United States, contains significant amounts of a phenolic compound, Hamamelitannin (HAMA). Green tea (GT) is a widely consumed plant that contains various catechins. Both plants have [...] Read more.
whISOBAX (WH), an extract of the witch-hazel plant that is native to the Northeast coast of the United States, contains significant amounts of a phenolic compound, Hamamelitannin (HAMA). Green tea (GT) is a widely consumed plant that contains various catechins. Both plants have been associated with antimicrobial effects. In this study we test the effects of these two plant extracts on the pathogenesis of staphylococci, and evaluate their effects on bacterial growth, biofilm formation, and toxin production. Our observations show that both extracts have antimicrobial effects against both strains of S. aureus and S. epidermidis tested, and that this inhibitory effect is synergistic. Also, we confirmed that this inhibitory effect does not depend on HAMA, but rather on other phenolic compounds present in WH and GT. In terms of biofilm inhibition, only WH exhibited an effect and the observed anti-biofilm effect was HAMA-depended. Finally, among the tested extracts, only WH exhibited an effect against Staphylococcal Enterotoxin A (SEA) production and this effect correlated to the HAMA present in WH. Our results suggest that GT and WH in combination can enhance the antimicrobial effects against staphylococci. However, only WH can control biofilm development and SEA production, due to the presence of HAMA. This study provides the initial rationale for the development of natural antimicrobials, to protect from staphylococcal colonization, infection, or contamination. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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15 pages, 1190 KiB  
Article
Microbial Growth and Biogenic Amine Production in a Balkan-Style Fresh Sausage during Refrigerated Storage under a CO2-Containing Anaerobic Atmosphere: Effect of the Addition of Zataria multiflora Essential Oil and Hops Extract
by Diego E. Carballo, Javier Mateo, Sonia Andrés, Francisco Javier Giráldez, Emiliano J. Quinto, Ali Khanjari, Sabina Operta and Irma Caro
Antibiotics 2019, 8(4), 227; https://doi.org/10.3390/antibiotics8040227 - 15 Nov 2019
Cited by 17 | Viewed by 3844
Abstract
Fresh sausages are highly perishable, and the preservatives allowed in these types of meat preparations are limited. Balkan-style fresh sausages were prepared in triplicate without antimicrobials (Control), with an aqueous hops extract (30 mL/kg), with Zataria multiflora Boiss essential oil (1 mL/kg), or [...] Read more.
Fresh sausages are highly perishable, and the preservatives allowed in these types of meat preparations are limited. Balkan-style fresh sausages were prepared in triplicate without antimicrobials (Control), with an aqueous hops extract (30 mL/kg), with Zataria multiflora Boiss essential oil (1 mL/kg), or a combination of both (15 and 0.5 mL/kg, respectively), and refrigerator-stored under a 20% CO2 and 80% N2 atmosphere. The spoilage microbial growth, i.e., lactic acid bacteria (LAB), Brochothrix thermosphacta, Enterobacteriaceae, Micrococcaceae, molds and yeasts, the pH value, and the production of biogenic amines in the sausages were monitored weekly and compared with a control sausage during a 35-day storage period. Furthermore, 349 colonies of presumptive LAB (isolated from the De Mann, Rogose-Sharpe agar plates) were identified using a MALDI-TOF-based method. Growth levels to ≈ 9 Log colony forming units (CFU) per g were reached by LAB, with a predominance of Lactobacillus sakei. Enterobacteriaceae and B. thermosphacta also showed significant growth (up to 6 Log CFU/g). Biogenic amine levels increased, and tyramine values overcame 250 mg/kg. The study could not demonstrate a significant effect of antimicrobial source treatments in any of the characteristics studied, and thus, the shelf-life of sausages. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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18 pages, 2528 KiB  
Article
Hibiscus Acid and Chromatographic Fractions from Hibiscus Sabdariffa Calyces: Antimicrobial Activity against Multidrug-Resistant Pathogenic Bacteria
by Lizbeth Anahí Portillo-Torres, Aurea Bernardino-Nicanor, Carlos Alberto Gómez-Aldapa, Simplicio González-Montiel, Esmeralda Rangel-Vargas, José Roberto Villagómez-Ibarra, Leopoldo González-Cruz, Humberto Cortés-López and Javier Castro-Rosas
Antibiotics 2019, 8(4), 218; https://doi.org/10.3390/antibiotics8040218 - 11 Nov 2019
Cited by 28 | Viewed by 5888
Abstract
The anti-microbial properties of acetone extracts from Hibiscus sabdariffa calyces, fractions isolated by silica gel chromatography and hibiscus acid purified from some of these fractions and additionally identified by nuclear magnetic resonance spectroscopy, mid-infrared spectroscopy and X-ray diffraction, were studied against both multidrug-resistant [...] Read more.
The anti-microbial properties of acetone extracts from Hibiscus sabdariffa calyces, fractions isolated by silica gel chromatography and hibiscus acid purified from some of these fractions and additionally identified by nuclear magnetic resonance spectroscopy, mid-infrared spectroscopy and X-ray diffraction, were studied against both multidrug-resistant Salmonella strains and pathogenic Escherichia coli bacteria. Gel diffusion was used to determine the anti-microbial effects. The mode of action of hibiscus acid was determined by crystal violet assay. Hibiscus acid and 17 of the 25 chromatographic fractions obtained, displayed an anti-microbial effect against all bacterial strains tested. Hibiscus acid showed a greater anti-microbial effect than the acetone extract against most of the bacteria strains, while chromatographic fractions IX–XIV exerted the greatest anti-microbial effect against all bacteria. The minimum inhibitory concentration of the acetone extract was 7 mg/mL, and the minimum bactericidal concentration was 10 mg/mL, while the corresponding values for hibiscus acid were 4–7 and 7 mg/mL, respectively. The results of the crystal violet assay indicate that hibiscus acid alters membrane permeability. Hibiscus acid is a potential alternative to control multidrug-resistant bacteria. Due to its ready availability and easy extraction from H. sabdariffa, hibiscus acid is potentially useful in the food industries. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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12 pages, 1075 KiB  
Article
Effects on Intestinal Mucosal Morphology, Productive Parameters and Microbiota Composition after Supplementation with Fermented Defatted Alperujo (FDA) in Laying Hens
by Agustín Rebollada-Merino, Carmen Bárcena, María Ugarte-Ruiz, Néstor Porras, Francisco J. Mayoral-Alegre, Irene Tomé-Sánchez, Lucas Domínguez and Antonio Rodríguez-Bertos
Antibiotics 2019, 8(4), 215; https://doi.org/10.3390/antibiotics8040215 - 09 Nov 2019
Cited by 17 | Viewed by 3825
Abstract
The olive oil sector is currently adapting its traditional function to also become a supplier of high-value by-products that possess antioxidant, anti-inflammatory and antimicrobial properties. In this study, we evaluated the effect of the fermented defatted alperujo (FDA) on the intestinal health of [...] Read more.
The olive oil sector is currently adapting its traditional function to also become a supplier of high-value by-products that possess antioxidant, anti-inflammatory and antimicrobial properties. In this study, we evaluated the effect of the fermented defatted alperujo (FDA) on the intestinal health of laying hens. The morphology of the duodenal and cecal mucosa, the composition of the intestinal microbiota and the productivity of a batch of laying hens were evaluated after FDA supplementation. At early life stages, significant differences (p < 0.001) were observed in duodenal villi height and in crypt depth of both the duodenum and the cecum in the FDA-supplemented group, indicating improved intestinal health in this group. Microbiota composition in the hatchery group supplemented with FDA had a higher abundance of Actinobacteria, Firmicutes and Proteobacteria, and higher bacterial diversity. During the production period, significant differences (p < 0.05) were observed in the number of broken eggs from the supplemented group. We conclude that FDA supplementation improves the absorption capacity of the intestinal mucosa and modifies the intestinal microbiota to favor a greater immune response, leading to an increase in egg production. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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12 pages, 769 KiB  
Article
13-(2-Methylbenzyl) Berberine Is a More Potent Inhibitor of MexXY-Dependent Aminoglycoside Resistance than Berberine
by Kenta Kotani, Mio Matsumura, Yuji Morita, Junko Tomida, Ryo Kutsuna, Kunihiko Nishino, Shuji Yasuike and Yoshiaki Kawamura
Antibiotics 2019, 8(4), 212; https://doi.org/10.3390/antibiotics8040212 - 06 Nov 2019
Cited by 9 | Viewed by 3725
Abstract
We previously showed that berberine attenuates MexXY efflux-dependent aminoglycoside resistance in Pseudomonas aeruginosa. Here, we aimed to synthesize berberine derivatives with higher MexXY inhibitory activities. We synthesized 11 berberine derivatives, of which 13-(2-methylbenzyl) berberine (13-o-MBB) but not its regiomers showed the most [...] Read more.
We previously showed that berberine attenuates MexXY efflux-dependent aminoglycoside resistance in Pseudomonas aeruginosa. Here, we aimed to synthesize berberine derivatives with higher MexXY inhibitory activities. We synthesized 11 berberine derivatives, of which 13-(2-methylbenzyl) berberine (13-o-MBB) but not its regiomers showed the most promising MexXY inhibitory activity. 13-o-MBB reduced the minimum inhibitory concentrations (MICs) of various aminoglycosides 4- to 128 fold for a highly multidrug resistant P. aeruginosa strain. Moreover, 13-o-MBB significantly reduced the MICs of gentamicin and amikacin in Achromobacter xylosoxidans and Burkholderia cepacia. The fractional inhibitory concentration indices indicated that 13-o-MBB acted synergistically with aminoglycosides in only MexXY-positive P. aeruginosa strains. Time-kill curves showed that 13-o-MBB or higher concentrations of berberine increased the bactericidal activity of gentamicin by inhibiting MexXY in P. aeruginosa. Our findings indicate that 13-o-MBB inhibits MexXY-dependent aminoglycoside drug resistance more strongly than berberine and that 13-o-MBB is a useful inhibitor of aminoglycoside drug resistance due to MexXY. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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16 pages, 909 KiB  
Article
Antibacterial Activities, Phytochemical Screening and Metal Analysis of Medicinal Plants: Traditional Recipes Used against Diarrhea
by Nasir Mahmood, Ruqia Nazir, Muslim Khan, Abdul Khaliq, Mohammad Adnan, Mohib Ullah and Hongyi Yang
Antibiotics 2019, 8(4), 194; https://doi.org/10.3390/antibiotics8040194 - 24 Oct 2019
Cited by 10 | Viewed by 5387
Abstract
The aim of this study was to explore the phytochemical composition, heavy metals analysis and the antibacterial activity of six medicinal plants i.e., Terminalia chebula Retz (fruits), Aegle marmelos L., (fruits), Curcuma longa L., (rhizomes), Syzygium aromaticum L., (flower buds), Piper nigrum L., [...] Read more.
The aim of this study was to explore the phytochemical composition, heavy metals analysis and the antibacterial activity of six medicinal plants i.e., Terminalia chebula Retz (fruits), Aegle marmelos L., (fruits), Curcuma longa L., (rhizomes), Syzygium aromaticum L., (flower buds), Piper nigrum L., (seeds), Cinnamomum cassia L., (barks) and its two remedial recipes (recipe 1 and 2) used against diarrhea obtained from the local herbal practitioners (Hakeems). A preliminary phytochemical screening of the above-mentioned plants extract in methanol, chloroform, n-hexane and distilled water revealed the presence of various constituents such as alkaloids, flavonoids, tannins and saponins by using standard procedures. The quantitative phytochemical studies shows that alkaloids, flavonoid and saponins were in maximum amount in Terminalia chebula. The concentration of Cd, Ni, Pb, Fe, Cr, Cu and Zn were investigated by using an atomic absorption spectrometer. The obtained analysis shows that Cr, Fe and Pb were present in the highest concentration in medicinal plants and their recipes. The antibacterial activities of the crude extract found in the recipes of methanol, chloroform, n-hexane and distilled water were analyzed by using agar well disc diffusion assay and minimum inhibitory concentration (MIC) by broth dilution method against four bacterial strains, namely, E. coli, Salmonella, Shigella and Methicillin-resistant Staphylococcus aureus (MRSA), respectively. The maximum zones of inhibition in methanol, water, chloroform and n-hexane extracts were seen in recipe 2 against Shigella (22.16 ± 0.47 mm), recipe 2 against Shigella (20.33 ± 0.24 mm), recipe 1 against Shigella (20.30 ± 0.29 mm) and recipe 2 against E. coli (30.23 ± 0.12 mm), respectively. Furthermore, the recipe extracts are more active against the tested bacterial strains than the extracts from individual plants. Therefore, it is concluded that the use of herbal plants and their recipes are the major source of drugs in a traditional medicinal system to cure different diseases. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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13 pages, 1072 KiB  
Article
Antifungal Agents Based on Chitosan Oligomers, ε-polylysine and Streptomyces spp. Secondary Metabolites against Three Botryosphaeriaceae Species
by Laura Buzón-Durán, Jesús Martín-Gil, Eduardo Pérez-Lebeña, David Ruano-Rosa, José L. Revuelta, José Casanova-Gascón, M. Carmen Ramos-Sánchez and Pablo Martín-Ramos
Antibiotics 2019, 8(3), 99; https://doi.org/10.3390/antibiotics8030099 - 20 Jul 2019
Cited by 24 | Viewed by 4548
Abstract
Grapevine trunk diseases (GTDs) are a major threat to the wine and grape industry. The aim of the study was to investigate the antifungal activity against Neofusicoccum parvum, Diplodia seriata, and Botryosphaeria dothidea of ε-polylysine, chitosan oligomers, their conjugates, Streptomyces rochei [...] Read more.
Grapevine trunk diseases (GTDs) are a major threat to the wine and grape industry. The aim of the study was to investigate the antifungal activity against Neofusicoccum parvum, Diplodia seriata, and Botryosphaeria dothidea of ε-polylysine, chitosan oligomers, their conjugates, Streptomyces rochei and S. lavendofoliae culture filtrates, and their binary mixtures with chitosan oligomers. In vitro mycelial growth inhibition tests suggest that the efficacy of these treatments, in particular those based on ε-polylysine and ε-polylysine:chitosan oligomers 1:1 w/w conjugate, against the three Botryosphaeriaceae species would be comparable to or higher than that of conventional synthetic fungicides. In the case of ε-polylysine, EC90 values as low as 227, 26.9, and 22.5 µg·mL−1 were obtained for N. parvum, D. seriata, and B. dothidea, respectively. Although the efficacy of the conjugate was slightly lower, with EC90 values of 507.5, 580.2, and 497.4 µg·mL−1, respectively, it may represent a more cost-effective option to the utilization of pure ε-polylysine. The proposed treatments may offer a viable and sustainable alternative for controlling GTDs. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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Review

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57 pages, 2088 KiB  
Review
Efficacy and Mechanism of Traditional Medicinal Plants and Bioactive Compounds against Clinically Important Pathogens
by Suresh Mickymaray
Antibiotics 2019, 8(4), 257; https://doi.org/10.3390/antibiotics8040257 - 09 Dec 2019
Cited by 87 | Viewed by 12184
Abstract
Traditional medicinal plants have been cultivated to treat various human illnesses and avert numerous infectious diseases. They display an extensive range of beneficial pharmacological and health effects for humans. These plants generally synthesize a diverse range of bioactive compounds which have been established [...] Read more.
Traditional medicinal plants have been cultivated to treat various human illnesses and avert numerous infectious diseases. They display an extensive range of beneficial pharmacological and health effects for humans. These plants generally synthesize a diverse range of bioactive compounds which have been established to be potent antimicrobial agents against a wide range of pathogenic organisms. Various research studies have demonstrated the antimicrobial activity of traditional plants scientifically or experimentally measured with reports on pathogenic microorganisms resistant to antimicrobials. The antimicrobial activity of medicinal plants or their bioactive compounds arising from several functional activities may be capable of inhibiting virulence factors as well as targeting microbial cells. Some bioactive compounds derived from traditional plants manifest the ability to reverse antibiotic resistance and improve synergetic action with current antibiotic agents. Therefore, the advancement of bioactive-based pharmacological agents can be an auspicious method for treating antibiotic-resistant infections. This review considers the functional and molecular roles of medicinal plants and their bioactive compounds, focusing typically on their antimicrobial activities against clinically important pathogens. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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30 pages, 612 KiB  
Review
Food Safety through Natural Antimicrobials
by Emiliano J. Quinto, Irma Caro, Luz H. Villalobos-Delgado, Javier Mateo, Beatriz De-Mateo-Silleras and María P. Redondo-Del-Río
Antibiotics 2019, 8(4), 208; https://doi.org/10.3390/antibiotics8040208 - 31 Oct 2019
Cited by 115 | Viewed by 11925
Abstract
Microbial pathogens are the cause of many foodborne diseases after the ingestion of contaminated food. Several preservation methods have been developed to assure microbial food safety, as well as nutritional values and sensory characteristics of food. However, the demand for natural antimicrobial agents [...] Read more.
Microbial pathogens are the cause of many foodborne diseases after the ingestion of contaminated food. Several preservation methods have been developed to assure microbial food safety, as well as nutritional values and sensory characteristics of food. However, the demand for natural antimicrobial agents is increasing due to consumers’ concern on health issues. Moreover, the use of antibiotics is leading to multidrug resistant microorganisms reinforcing the focus of researchers and the food industry on natural antimicrobials. Natural antimicrobial compounds from plants, animals, bacteria, viruses, algae and mushrooms are covered. Finally, new perspectives from researchers in the field and the interest of the food industry in innovations are reviewed. These new approaches should be useful for controlling foodborne bacterial pathogens; furthermore, the shelf-life of food would be extended. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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24 pages, 2189 KiB  
Review
Actinobacteria Derived from Algerian Ecosystems as a Prominent Source of Antimicrobial Molecules
by Ibtissem Djinni, Andrea Defant, Mouloud Kecha and Ines Mancini
Antibiotics 2019, 8(4), 172; https://doi.org/10.3390/antibiotics8040172 - 01 Oct 2019
Cited by 20 | Viewed by 5882
Abstract
Actinobacteria, in particular “rare actinobacteria” isolated from extreme ecosystems, remain the most inexhaustible source of novel antimicrobials, offering a chance to discover new bioactive metabolites. This is the first overview on actinobacteria isolated in Algeria since 2002 to date with the aim to [...] Read more.
Actinobacteria, in particular “rare actinobacteria” isolated from extreme ecosystems, remain the most inexhaustible source of novel antimicrobials, offering a chance to discover new bioactive metabolites. This is the first overview on actinobacteria isolated in Algeria since 2002 to date with the aim to present their potential in producing bioactive secondary metabolites. Twenty-nine new species and one novel genus have been isolated, mainly from the Saharan soil and palm groves, where 37.93% of the most abundant genera belong to Saccharothrix and Actinopolyspora. Several of these strains were found to produce antibiotics and antifungal metabolites, including 17 new molecules among the 50 structures reported, and some of these antibacterial metabolites have shown interesting antitumor activities. A series of approaches used to enhance the production of bioactive compounds is also presented as the manipulation of culture media by both classical methods and modeling designs through statistical strategies and the associations with diverse organisms and strains. Focusing on the Algerian natural sources of antimicrobial metabolites, this work is a representative example of the potential of a closely combined study on biology and chemistry of natural products. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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14 pages, 2651 KiB  
Review
Natural Product Type III Secretion System Inhibitors
by Heather A. Pendergrass and Aaron E. May
Antibiotics 2019, 8(4), 162; https://doi.org/10.3390/antibiotics8040162 - 24 Sep 2019
Cited by 20 | Viewed by 7402
Abstract
Many known inhibitors of the bacterial type III secretion system (T3SS), a virulence factor used by pathogenic bacteria to infect host cells, are natural products. These compounds, produced by bacteria, fungi, and plants, may have developed as prophylactic treatments for potential attack by [...] Read more.
Many known inhibitors of the bacterial type III secretion system (T3SS), a virulence factor used by pathogenic bacteria to infect host cells, are natural products. These compounds, produced by bacteria, fungi, and plants, may have developed as prophylactic treatments for potential attack by bacterial pathogens or as an attempt by symbiotic organisms to protect their hosts. Regardless, better understanding of the structures and mechanisms of action of these compounds may open opportunities for drug development against diseases caused by pathogens utilizing the T3SS. This review will cover selected known natural products of the T3SS and detail what is known of their origin and mechanism of action. These inhibitors highlight nature’s ability to modulate interactions between organisms at a cellular level. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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19 pages, 1214 KiB  
Review
Do Global Regulators Hold the Key to Production of Bacterial Secondary Metabolites?
by Sudarshan Singh Thapa and Anne Grove
Antibiotics 2019, 8(4), 160; https://doi.org/10.3390/antibiotics8040160 - 23 Sep 2019
Cited by 13 | Viewed by 5675
Abstract
The emergence of multiple antibiotic resistant bacteria has pushed the available pool of antibiotics to the brink. Bacterial secondary metabolites have long been a valuable resource in the development of antibiotics, and the genus Burkholderia has recently emerged as a source of novel [...] Read more.
The emergence of multiple antibiotic resistant bacteria has pushed the available pool of antibiotics to the brink. Bacterial secondary metabolites have long been a valuable resource in the development of antibiotics, and the genus Burkholderia has recently emerged as a source of novel compounds with antibacterial, antifungal, and anti-cancer activities. Genome mining has contributed to the identification of biosynthetic gene clusters, which encode enzymes that are responsible for synthesis of such secondary metabolites. Unfortunately, these large gene clusters generally remain silent or cryptic under normal laboratory settings, which creates a hurdle in identification and isolation of these compounds. Various strategies, such as changes in growth conditions and antibiotic stress, have been applied to elicit the expression of these cryptic gene clusters. Although a number of compounds have been isolated from different Burkholderia species, the mechanisms by which the corresponding gene clusters are regulated remain poorly understood. This review summarizes the activity of well characterized secondary metabolites from Burkholderia species and the role of local regulators in their synthesis, and it highlights recent evidence for the role of global regulators in controlling production of secondary metabolites. We suggest that targeting global regulators holds great promise for the awakening of cryptic gene clusters and for developing better strategies for discovery of novel antibiotics. Full article
(This article belongs to the Special Issue Natural Compounds as Antimicrobial Agents)
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