Editorial

4 pages, 220 KiB

Open AccessEditorial

New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action

by Jorge H. Leitão

Antibiotics 2020, 9(8), 471; https://doi.org/10.3390/antibiotics9080471 - 01 Aug 2020

Cited by 4 | Viewed by 2622

The worldwide emergence of microbial resistance to available antibiotics presents a global threat to public health and health systems. This special issue aimed to gather papers describing novel antibiotics, originating form chemical synthesis, repurposing of existent drugs, or from natural sources like plant [...] Read more.

The worldwide emergence of microbial resistance to available antibiotics presents a global threat to public health and health systems. This special issue aimed to gather papers describing novel antibiotics, originating form chemical synthesis, repurposing of existent drugs, or from natural sources like plant extracts, herbs and spices. A total of 13 papers were published, covering a wide range of topic, including antimicrobial resistance surveillance studies; synthesis of novel molecules with antimicrobial activities; modification or repurposing of already existing molecules, plant-derived active extracts, and molecules; the effects of antimicrobial therapy on microbiota; and the investigation of novel formulations for human and veterinary uses. After decades of antibiotics discovery decline, antibiotics discovery is boosting. Recent developments of post genomics approaches and bioinformatics tools will most certainly turn the tide in the discovery and development of antimicrobials in this exciting field. Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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14 pages, 2992 KiB

Open AccessArticle

A Tale of Two Ends: Repurposing Metallic Compounds from Anti-Tumour Agents to Effective Antibacterial Activity

by Daniela Alves Ferreira, Luísa M. D. R. S. Martins, Alexandra R. Fernandes and Marta Martins

Antibiotics 2020, 9(6), 321; https://doi.org/10.3390/antibiotics9060321 - 11 Jun 2020

Cited by 4 | Viewed by 2553

Abstract

The rise in antibiotic resistance coupled with the gap in the discovery of active molecules has driven the need for more effective antimicrobials while focusing the attention into the repurpose of already existing drugs. Here, we evaluated the potential antibacterial activity of one [...] Read more.

The rise in antibiotic resistance coupled with the gap in the discovery of active molecules has driven the need for more effective antimicrobials while focusing the attention into the repurpose of already existing drugs. Here, we evaluated the potential antibacterial activity of one cobalt and two zinc metallic compounds previously reported as having anticancer properties. Compounds were tested against a range of Gram-positive and -negative bacteria. The determination of the minimum inhibitory and bactericidal concentrations (MIC/MBC) of the drugs were used to assess their potential antibacterial activity and their effect on bacterial growth. Motility assays were conducted by exposing the bacteria to sub-MIC of each of the compounds. The effect of sub-MIC of the compounds on the membrane permeability was measured by ethidium bromide (EtBr) accumulation assay. Cell viability assays were performed in human cells. Compound TS262 was the most active against the range of bacteria tested. No effect was observed on the motility or accumulation of EtBr for any of the bacteria tested. Cell viability assays demonstrated that the compounds showed a decrease in cell viability at the MIC. These results are promising, and further studies on these compounds can lead to the development of new effective antimicrobials. Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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18 pages, 4844 KiB

Open AccessArticle

Antimicrobial Isoflavones and Derivatives from Erythrina (Fabaceae): Structure Activity Perspective (Sar & Qsar) on Experimental and Mined Values Against Staphylococcus aureus

by Nicholas J. Sadgrove, Tiago B. Oliveira, Gugulethu P. Khumalo, Sandy F. van Vuuren and Ben-Erik van Wyk

Antibiotics 2020, 9(5), 223; https://doi.org/10.3390/antibiotics9050223 - 30 Apr 2020

Cited by 21 | Viewed by 3566

Abstract

Prenylated (iso)flavonoids, -flavans and pterocarpans from taxa in Erythrina are repeatedly flagged as potent antimicrobial compounds. In the current study, bark from E. lysistemon was extracted and seven isoflavone derivatives were purified: erybraedin A (1), phaseollidin (2), abyssinone V-4′ [...] Read more.

Prenylated (iso)flavonoids, -flavans and pterocarpans from taxa in Erythrina are repeatedly flagged as potent antimicrobial compounds. In the current study, bark from E. lysistemon was extracted and seven isoflavone derivatives were purified: erybraedin A (1), phaseollidin (2), abyssinone V-4′ methyl ether (3), eryzerin C (4), alpumisoflavone (5), cristacarpin (6) and lysisteisoflavone (7). Minimum inhibition concentration (MIC) values were determined against a range of species of bacteria (skin pathogens), then values for another 67 derivatives from Erythrina, only against Staphylococcus aureus, were mined from the literature. Of the seven isolates, MIC values widely ranged from 1–600 μg/mL, with no obvious pattern of selectivity for Gram-types. Nevertheless, using the mined and experimentally determined values against S. aureus, Klekota-Roth fragments (Structure Activity Relationship: SAR) were determined then used as molecular descriptors to make a ‘decision tree’ based on structural characters inspired by the classes of antimicrobial potency (classes A-D). Furthermore, to make quantitative predictions of MIC values (Quantitative SAR: QSAR) ‘pace regression’ was utilized and validated (R² = 0.778, Q² = 0.727 and P² = 0.555). Evidently, the position and degree of prenylation is important; however, the presence of hydroxyl groups at positions 5 and 7 in ring A and 4′ in ring B is associated with lower MIC values. While antimicrobial results continue to validate the traditional use of E. lysistemon extracts (or Erythrina generally) in therapeutic applications consistent with anti-infection, it is surprising that this class of compound is not being utilized more often in general industry applications, such as food or cosmetic preservation, or in topical antimicrobial creams. Prenylated (iso)flavonoids are derived from several other Genera, such as Dorstenia (Moraceae), Ficus (Moraceae), Glycyrrhiza (Fabaceae), Paulownia (Lamiales) or Pomifera (Moraceae). Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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15 pages, 2151 KiB

Open AccessArticle

Screening and Molecular Docking of Novel Benzothiazole Derivatives as Potential Antimicrobial Agents

by Mohamed A. Morsy, Enas M. Ali, Mahmoud Kandeel, Katharigatta N. Venugopala, Anroop B. Nair, Khaled Greish and Mahmoud El-Daly

Antibiotics 2020, 9(5), 221; https://doi.org/10.3390/antibiotics9050221 - 29 Apr 2020

Cited by 50 | Viewed by 4889

Abstract

The burden of antibiotic resistance necessitates a continued search for new antimicrobials. We evaluated the antimicrobial activities of novel benzothiazoles synthesized by our group. Antibacterial activity was evaluated in vitro in Staphylococcus aureus, Bacillus subtilis, and Escherichia coli, while the [...] Read more.

The burden of antibiotic resistance necessitates a continued search for new antimicrobials. We evaluated the antimicrobial activities of novel benzothiazoles synthesized by our group. Antibacterial activity was evaluated in vitro in Staphylococcus aureus, Bacillus subtilis, and Escherichia coli, while the antifungal activity was tested in Candida albicans and Aspergillus niger, and expressed as the minimum inhibitory concentration (MIC; µg/mL). MIC values of benzothiazole compounds ranged from 25 to 200 µg/mL. Compounds 3 and 4 gave high antibacterial and moderate antifungal activities, while 10 and 12 showed moderate activity against all tested organisms. In addition, some benzothiazole compounds significantly suppressed the activity of Escherichia coli dihydroorotase and inhibited the dimorphic transition of Candida albicans. Moreover, the active benzothiazole compounds induced DNA and protein leakage in Aspergillus niger spores. Molecular interactions of benzothiazole derivatives with dihydroorotase revealed the formation of hydrogen bonds with the active site residues LEU222 or ASN44. Strong hydrophobic interactions of the bulky thiazole and naphthalene rings at the entrance to the active site might interfere with the access of substrates to their binding sites, which results in dihydroorotase inhibition. Thus, inhibition of dihydroorotase might contribute to the observed antimicrobial actions of these compounds. Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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10 pages, 1304 KiB

Open AccessArticle

High-Value Plant Species Used for the Treatment of “Fever” by the Karen Hill Tribe People

by Methee Phumthum and Nicholas J. Sadgrove

Antibiotics 2020, 9(5), 220; https://doi.org/10.3390/antibiotics9050220 - 29 Apr 2020

Cited by 14 | Viewed by 3079

Abstract

The symptom “fever” is generally not itself a terminal condition. However, it does occur with common mild to severe ailments afflicting the world population. Several allopathic medicines are available to attenuate fever by targeting the pathogen or the symptom itself. However, many people [...] Read more.

The symptom “fever” is generally not itself a terminal condition. However, it does occur with common mild to severe ailments afflicting the world population. Several allopathic medicines are available to attenuate fever by targeting the pathogen or the symptom itself. However, many people in marginal civilizations are obligated to use locally grown medicinal plants due to limited access to common pharmaceuticals. The Karen ethnic group is the biggest ethnic minority group in the hill-tribes of Thailand. They utilise a vast repertoire of medicinal plant species. Since many modern drugs were discovered out of traditional therapies, it is possible to discover new allopathic drugs in the treatment of fever and associated pathogens from the Karen people. Thus, this study aims to identify and record the ethnomedicinal plants they used for the treatment of “fever”. The names of plants used by the Thai Karen people for the treatment of fever were mined from publications on ethnomedicinal uses. Useful plant species and families were identified using the Cultural Importance Index (CI). With the mined data, 125 plant species from 52 families were identified, distributed across 25 Karen villages. A chemical cross-examination of these species provided valuable insights into chemical classes worthy of further investigation in the context of fever and associated pathogens. Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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9 pages, 1645 KiB

Open AccessArticle

Prevalence and Antimicrobial Susceptibility Patterns of Bacterial Pathogens in Urinary Tract Infections in University Hospital of Campania “Luigi Vanvitelli” between 2017 and 2018

by Veronica Folliero, Pina Caputo, Maria Teresa Della Rocca, Annalisa Chianese, Marilena Galdiero, Maria R. Iovene, Cameron Hay, Gianluigi Franci and Massimiliano Galdiero

Antibiotics 2020, 9(5), 215; https://doi.org/10.3390/antibiotics9050215 - 28 Apr 2020

Cited by 34 | Viewed by 5734

Abstract

Urinary tract infections (UTIs) are the most common and expensive health problem globally. The treatment of UTIs is difficult owing to the onset of antibiotic-resistant bacterial strains. The aim of this study was to define the incidence of infections, identify the bacteria responsible, [...] Read more.

Urinary tract infections (UTIs) are the most common and expensive health problem globally. The treatment of UTIs is difficult owing to the onset of antibiotic-resistant bacterial strains. The aim of this study was to define the incidence of infections, identify the bacteria responsible, and identify the antimicrobial resistance profile. Patients of all ages and both sexes were included in the study, all admitted to University Hospital of Campania “Luigi Vanvitelli”, between January 2017 and December 2018. Bacterial identification and antibiotic susceptibility testing were performed using matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and Phoenix BD. Among the 1745 studied patients, 541 (31%) and 1204 (69%) were positive and negative for bacterial growth, respectively. Of 541 positive patients, 325 (60%) were females, while 216 (39.9%) were males. The largest number of positive subjects was recorded in the elderly (>61 years). Among the pathogenic strains, 425 (78.5%) were Gram-negative, 107 (19.7%) were Gram-positive, and 9 (1.7%) were Candida species. The most isolated Gram-negative strain is Escherichia coli (E. coli) (53.5%). The most frequent Gram-positive strain was Enterococcus faecalis (E. faecalis) (12.9%). Gram-negative bacteria were highly resistant to ampicillin, whereas Gram-positive bacteria were highly resistant to erythromycin. Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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11 pages, 2317 KiB

Open AccessArticle

Polyphasic Validation of a Nisin-Biogel to Control Canine Periodontal Disease

by Eva Cunha, Ferdinando Bernardino Freitas, Berta São Braz, Jorge Moreira da Silva, Luís Tavares, Ana Salomé Veiga and Manuela Oliveira

Antibiotics 2020, 9(4), 180; https://doi.org/10.3390/antibiotics9040180 - 14 Apr 2020

Cited by 14 | Viewed by 3227

Abstract

Background: Periodontal disease (PD) is a highly prevalent inflammatory disease in dogs. This disease is initiated by a polymicrobial biofilm on the teeth surface, whose control includes its prevention and removal. Recently, it was shown that nisin displays antimicrobial activity against canine PD-related [...] Read more.

Background: Periodontal disease (PD) is a highly prevalent inflammatory disease in dogs. This disease is initiated by a polymicrobial biofilm on the teeth surface, whose control includes its prevention and removal. Recently, it was shown that nisin displays antimicrobial activity against canine PD-related bacteria. Moreover, guar gum biogel has shown to be a promising topical delivery system for nisin. Methods: In this study we aimed to evaluate the antimicrobial activity of the nisin-biogel in the presence of canine saliva and after a 24-month storage, at different conditions, using a canine oral enterococci collection. We also studied the nisin-biogel cytotoxicity using a Vero cell line and canine primary intestinal fibroblasts. Results: The presence of saliva hampers nisin-biogel antimicrobial activity, and higher nisin concentrations were required for an effective activity. A significant reduction (p ≤ 0.05) in inhibitory activity was observed for nisin-biogel solutions stored at 37 °C, over a 24-month period, which was not observed with the other conditions. The nisin-biogel showed no cytotoxicity against the cells tested at concentrations up to 200 µg/mL. Conclusions: Our results confirmed the potential of the nisin-biogel for canine PD control, supporting the development of an in vivo clinical trial. Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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16 pages, 1574 KiB

Open AccessArticle

New Labdanes with Antimicrobial and Acaricidal Activity: Terpenes of Callitris and Widdringtonia (Cupressaceae)

by Nicholas J. Sadgrove, Haytham Senbill, Ben-Erik Van Wyk and Ben W. Greatrex

Antibiotics 2020, 9(4), 173; https://doi.org/10.3390/antibiotics9040173 - 11 Apr 2020

Cited by 11 | Viewed by 3541

Abstract

In spite of the evidence for antimicrobial and acaricidal effects in ethnobotanical reports of Callitris and Widdringtonia, the diterpene acids from Widdringtonia have never been described and no comparison to the Australian clade sister genus Callitris has been made. The critically endangered [...] Read more.

In spite of the evidence for antimicrobial and acaricidal effects in ethnobotanical reports of Callitris and Widdringtonia, the diterpene acids from Widdringtonia have never been described and no comparison to the Australian clade sister genus Callitris has been made. The critically endangered South African Clanwilliam cedar, Widdringtonia wallichii (syn. W. cedarbergensis), of the Cederberg Mountains was once prized for its enduring fragrant timbers and an essential oil that gives an aroma comparable to better known Mediterranean cedars, predominantly comprised by widdrol, cedrol, and thujopsene. In South Africa, two other ‘cedars’ are known, which are called W. nodiflora and W. schwarzii, but, until now, their chemical similarity to W. wallichii has not been investigated. Much like Widdringtonia, Callitris was once prized for its termite resistant timbers and an ‘earthy’ essential oil, but predominantly guaiol. The current study demonstrates that the essential oils were similar across all three species of Widdringtonia and two known non-volatile diterpene acids were identified in leaves: the pimaradiene sandaracopimaric acid (1) and the labdane Z-communic acid (2) with a lower yield of the E-isomer (3). Additionally, in the leaves of the three species, the structures of five new antimicrobial labdanes were assigned: 12-hydroxy-8R,17-epoxy-isocommunic acid (4), 8S-formyl-isocommunic acid (5), 8R,17-epoxy-isocommunic acid (6), 8R-17R-epoxy-E-communic acid (7), and 8R-17-epoxy-E-communic acid (8). Australian Callitris columellaris (syn. C. glaucophylla) also produced 1 and its isomer isopimaric acid, pisiferal (9), and pisiferic acid (10) from its leaves. Callitris endlicheri (Parl.) F.M.Bailey yielded isoozic acid (11) as the only major diterpene. Diterpenes 4–6, pisiferic acid (10), spathulenol, and guaiol (12) demonstrated antimicrobial and acaricidal activity. Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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12 pages, 1621 KiB

Open AccessArticle

Deep Functional Profiling Facilitates the Evaluation of the Antibacterial Potential of the Antibiotic Amicoumacin

by Stanislav S. Terekhov, Anton S. Nazarov, Yuliana A. Mokrushina, Margarita N. Baranova, Nadezhda A. Potapova, Maja V. Malakhova, Elena N. Ilina, Ivan V. Smirnov and Alexander G. Gabibov

Antibiotics 2020, 9(4), 157; https://doi.org/10.3390/antibiotics9040157 - 02 Apr 2020

Cited by 13 | Viewed by 4993

Abstract

The global spread of antibiotic resistance is forcing the scientific community to find new molecular strategies to counteract it. Deep functional profiling of microbiomes provides an alternative source for the discovery of novel antibiotic producers and probiotics. Recently, we implemented this ultrahigh-throughput screening [...] Read more.

The global spread of antibiotic resistance is forcing the scientific community to find new molecular strategies to counteract it. Deep functional profiling of microbiomes provides an alternative source for the discovery of novel antibiotic producers and probiotics. Recently, we implemented this ultrahigh-throughput screening approach for the isolation of Bacillus pumilus strains efficiently producing the ribosome-targeting antibiotic amicoumacin A (Ami). Proteomics and metabolomics revealed essential insight into the activation of Ami biosynthesis. Here, we applied omics to boost Ami biosynthesis, providing the optimized cultivation conditions for high-scale production of Ami. Ami displayed a pronounced activity against Lactobacillales and Staphylococcaceae, including methicillin-resistant Staphylococcus aureus (MRSA) strains, which was determined using both classical and massive single-cell microfluidic assays. However, the practical application of Ami is limited by its high cytotoxicity and particularly low stability. The former is associated with its self-lactonization, serving as an improvised intermediate state of Ami hydrolysis. This intramolecular reaction decreases Ami half-life at physiological conditions to less than 2 h, which is unprecedented for a terminal amide. While we speculate that the instability of Ami is essential for Bacillus ecology, we believe that its stable analogs represent attractive lead compounds both for antibiotic discovery and for anticancer drug development. Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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13 pages, 2174 KiB

Open AccessArticle

Rifaximin Alleviates Endotoxemia with Decreased Serum Levels of Soluble CD163 and Mannose Receptor and Partial Modification of Gut Microbiota in Cirrhotic Patients

by Kosuke Kaji, Soichiro Saikawa, Hiroaki Takaya, Yukihisa Fujinaga, Masanori Furukawa, Koh Kitagawa, Takahiro Ozutsumi, Daisuke Kaya, Yuki Tsuji, Yasuhiko Sawada, Hideto Kawaratani, Kei Moriya, Tadashi Namisaki, Takemi Akahane, Akira Mitoro and Hitoshi Yoshiji

Antibiotics 2020, 9(4), 145; https://doi.org/10.3390/antibiotics9040145 - 29 Mar 2020

Cited by 34 | Viewed by 3931

Abstract

Rifaximin is a poorly absorbable antibiotic against hepatic encephalopathy (HE). This observational study aimed to elucidate the effect of rifaximin on intestinal permeability and gut microbiota in patients with decompensated cirrhosis. Thirty patients with decompensated cirrhosis were assessed by ammonia level, neuropsychological testing, [...] Read more.

Rifaximin is a poorly absorbable antibiotic against hepatic encephalopathy (HE). This observational study aimed to elucidate the effect of rifaximin on intestinal permeability and gut microbiota in patients with decompensated cirrhosis. Thirty patients with decompensated cirrhosis were assessed by ammonia level, neuropsychological testing, endotoxin activity (EA), and serum proinflammatory cytokines at baseline and after four weeks of rifaximin treatment (1200 mg/day). Intestinal permeability was indicated by serum soluble CD163 (sCD163), mannose receptor (sMR), and zonulin levels. To evaluate the gut microbiome, 16S ribosomal RNA gene sequencing was applied. Rifaximin ameliorated hyperammonemia and cognitive dysfunction, although it did not change the serum proinflammatory cytokine levels. It decreased EA levels as well as serum levels of sCD163 and sMR, but not zonulin, and both decreases in sCD163 and sMR showed positive correlations with EA decrease (ΔsCD163: Correlation coefficient (R) = 0.680, p = 0.023; ΔsMR: R = 0.613, p = 0.014, vs. ΔEA). Gut microbial analysis revealed that the richness and complexity of species were unchanged while the abundance of the Streptococcus genus was reduced after treatment with rifaximin. Collectively, rifaximin alleviated HE and endotoxemia with improved intestinal hyperpermeability in patients with decompensated cirrhosis, and this effect is partially involved in a gut microbial change. Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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15 pages, 1229 KiB

Open AccessArticle

Pexiganan in Combination with Nisin to Control Polymicrobial Diabetic Foot Infections

by Diana Gomes, Raquel Santos, Rui S. Soares, Solange Reis, Sandra Carvalho, Pedro Rego, Maria C. Peleteiro, Luís Tavares and Manuela Oliveira

Antibiotics 2020, 9(3), 128; https://doi.org/10.3390/antibiotics9030128 - 20 Mar 2020

Cited by 28 | Viewed by 4979

Abstract

Diabetic foot ulcers (DFUs) are major complications of Diabetes mellitus being responsible for significant morbidity and mortality. DFUs frequently become chronically infected by a complex community of bacteria, including multidrug-resistant and biofilm-producing strains of Staphylococcus aureus and Pseudomonas aeruginosa. Diabetic foot infections [...] Read more.

Diabetic foot ulcers (DFUs) are major complications of Diabetes mellitus being responsible for significant morbidity and mortality. DFUs frequently become chronically infected by a complex community of bacteria, including multidrug-resistant and biofilm-producing strains of Staphylococcus aureus and Pseudomonas aeruginosa. Diabetic foot infections (DFI) are often recalcitrant to conventional antibiotics and alternative treatment strategies are urgently needed. Antimicrobial Peptides (AMPs), such as pexiganan and nisin, have been increasingly investigated and reported as effective antimicrobial agents. Here, we evaluated the antibacterial potential of pexiganan and nisin used in combination (dual-AMP) to control the growth of planktonic and biofilm co-cultures of S. aureus and P. aeruginosa clinical strains, co-isolated from a DFU. A DFU collagen three-dimensional (3D) model was used to evaluate the distribution and efficacy of AMPs locally delivered into the model. The concentration of pexiganan required to inhibit and eradicate both planktonic and biofilm-based bacterial cells was substantially reduced when used in combination with nisin. Moreover, incorporation of both AMPs in a guar gum delivery system (dual-AMP biogel) did not affect the dual-AMP antimicrobial activity. Importantly, the application of the dual-AMP biogel resulted in the eradication of the S. aureus strain from the model. In conclusion, data suggest that the local application of the dual-AMPs biogel constitutes a potential complementary therapy for the treatment of infected DFU. Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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10 pages, 1738 KiB

Open AccessArticle

Modified Aminoglycosides Bind Nucleic Acids in High-Molecular-Weight Complexes

by Lanqing Ying, Hongkun Zhu, Marina Y. Fosso, Sylvie Garneau-Tsodikova and Kurt Fredrick

Antibiotics 2020, 9(2), 93; https://doi.org/10.3390/antibiotics9020093 - 21 Feb 2020

Cited by 3 | Viewed by 2818

Abstract

Aminoglycosides represent a large group of antibiotics well known for their ability to target the bacterial ribosome. In studying 6”-substituted variants of the aminoglycoside tobramycin, we serendipitously found that compounds with C₁₂ or C₁₄ linear alkyl substituents potently inhibit reverse transcription [...] Read more.

Aminoglycosides represent a large group of antibiotics well known for their ability to target the bacterial ribosome. In studying 6”-substituted variants of the aminoglycoside tobramycin, we serendipitously found that compounds with C₁₂ or C₁₄ linear alkyl substituents potently inhibit reverse transcription in vitro. Initial observations suggested specific inhibition of reverse transcriptase. However, further analysis showed that these and related compounds bind nucleic acids with high affinity, forming high-molecular weight complexes. Stable complex formation is observed with DNA or RNA in single- or double-stranded form. Given the amphiphilic nature of these aminoglycoside derivatives, they likely form micelles and/or vesicles with surface-bound nucleic acids. Hence, these compounds may be useful tools to localize nucleic acids to surfaces or deliver nucleic acids to cells or organelles. Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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25 pages, 7543 KiB

Open AccessArticle

Antifungal, Antitumoral and Antioxidant Potential of the Danube Delta Nymphaea alba Extracts

by Mihaela Cudalbeanu, Bianca Furdui, Geta Cârâc, Vasilica Barbu, Alina Viorica Iancu, Fernanda Marques, Jorge Humberto Leitão, Sílvia Andreia Sousa and Rodica Mihaela Dinica

Antibiotics 2020, 9(1), 7; https://doi.org/10.3390/antibiotics9010007 - 21 Dec 2019

Cited by 21 | Viewed by 5574

Abstract

This study aimed to explore for the first time the biological properties such as antifungal, antitumoral and antioxidant of Danube Delta Nymphaea alba (N. alba) leaf and root methanolic extracts. The toxicity studies of N. alba extracts showed no inhibitory effect [...] Read more.

This study aimed to explore for the first time the biological properties such as antifungal, antitumoral and antioxidant of Danube Delta Nymphaea alba (N. alba) leaf and root methanolic extracts. The toxicity studies of N. alba extracts showed no inhibitory effect on wheat seed germination by evaluating the most sensitive physiological parameters (Germination %, Germination index, Vigor index) and using confocal laser scanning microscopy images. The analyzed extracts were found to have high antifungal activity against Candida glabrata with MIC values of 1.717 µg/mL for leaf and 1.935 µg/mL for root. The antitumor activity of the both extracts against A2780/A2780cisR ovarian, LNCaP prostate and MCF-7 breast cancer cells was promising with IC₅₀ values ranging from 23–274 µg/mL for leaf and 18–152 µg/mL for root, and the combination of N. alba extracts with cisplatin showed a synergistic effect (coefficient of drug interaction <1). The antioxidant properties were assessed by β-carotene bleaching, ABTS and FRAP assays and cyclic voltammetry. Quercetin, the most prominent antioxidant, was quantified in very good yields by spectroelectrochemical assay. Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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16 pages, 4137 KiB

Open AccessArticle

Investigations into the Structure/Antibacterial Activity Relationships of Cyclam and Cyclen Derivatives

by Luis G. Alves, João F. Portel, Sílvia A. Sousa, Olga Ferreira, Stephanie Almada, Elisabete R. Silva, Ana M. Martins and Jorge H. Leitão

Antibiotics 2019, 8(4), 224; https://doi.org/10.3390/antibiotics8040224 - 14 Nov 2019

Cited by 9 | Viewed by 3687

Abstract

A series of cyclam- and cyclen-derived salts are described in the present work; they were designed specifically to gain insights into their structure and antibacterial activity towards Staphylococcus aureus and Escherichia coli, used respectively, as Gram-positive and Gram-negative model organisms. The newly [...] Read more.

A series of cyclam- and cyclen-derived salts are described in the present work; they were designed specifically to gain insights into their structure and antibacterial activity towards Staphylococcus aureus and Escherichia coli, used respectively, as Gram-positive and Gram-negative model organisms. The newly synthesized compounds are monosubstituted and trans-disubstituted tetraazamacrocycles that display benzyl, methylbenzyl, trifluoromethylbenzyl, or trifluoroethylbenzyl substituents appended on the nitrogen atoms of the macrocyclic ring. The results obtained show that the chemical nature, polarity, and substitution patterns of the benzyl groups, as well as the number of pendant arms, are critical parameters for the antibacterial activity of the cyclam-based salts. The most active compounds against both bacterial strains were the trans-disubstituted cyclam salts displaying CF₃ groups in the para-position of the aromatic rings of the macrocyclic pendant arms. The analogous cyclen species presents a lower activity, revealing that the size of the macrocyclic backbone is an important requirement for the antibacterial activity of the tetraazamacrocycles. The nature of the anionic counterparts present on the salts was found to play a minor role in the antibacterial activity. Full article

(This article belongs to the Special Issue New Insights into Antibacterial Compounds: From Synthesis and Discovery to Molecular Mechanisms of Action)

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