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Open AccessArticle

A Mitochondria-Penetrating Peptide Exerts Potent Anti-Plasmodium Activity and Localizes at Parasites’ Mitochondria

by

Sangdao Somsri

,

Mathirut Mungthin

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Natthaporn Klubthawee

,

Poom Adisakwattana

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Warunee Hanpithakpong

and

Ratchaneewan Aunpad

Antibiotics 2021, 10(12), 1560; https://doi.org/10.3390/antibiotics10121560 - 20 Dec 2021

Cited by 5 | Viewed by 2355

Abstract

Mitochondria are considered a novel drug target as they play a key role in energy production and programmed cell death of eukaryotic cells. The mitochondria of malaria parasites differ from those of their vertebrate hosts, contributing to the drug selectivity and the development [...] Read more.

Mitochondria are considered a novel drug target as they play a key role in energy production and programmed cell death of eukaryotic cells. The mitochondria of malaria parasites differ from those of their vertebrate hosts, contributing to the drug selectivity and the development of antimalarial drugs. (F_xr)₃, a mitochondria-penetrating peptide or MPP, entered malaria-infected red cells without disrupting the membrane and subsequently killed the blood stage of P. falciparum parasites. The effects were more potent on the late stages than on the younger stages. Confocal microscopy showed that the (F_xr)₃ intensely localized at the parasite mitochondria. (F_xr)₃ highly affected both the lab-strain, chloroquine-resistant K1, and freshly isolated malaria parasites. (F_xr)₃ (1 ng/mL to 10 μg/mL) was rarely toxic towards various mammalian cells, i.e., mouse fibroblasts (L929), human leukocytes and erythrocytes. At a thousand times higher concentration (100 μg/mL) than that of the antimalarial activity, cytotoxicity and hemolytic activity of (F_xr)₃ were observed. Compared with the known antimalarial drug, atovaquone, (F_xr)₃ exhibited more rapid killing activity. This is the first report on antimalarial activity of (F_xr)₃, showing localization at parasites’ mitochondria. Full article

(This article belongs to the Special Issue Research and Development of Antibiotics)

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Open AccessArticle

Seconeolitsine, the Novel Inhibitor of DNA Topoisomerase I, Protects against Invasive Pneumococcal Disease Caused by Fluoroquinolone-Resistant Strains

by

Jose Manuel Tirado-Vélez

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and

Antibiotics 2021, 10(5), 573; https://doi.org/10.3390/antibiotics10050573 - 13 May 2021

Cited by 1 | Viewed by 1571

Abstract

Antibiotic resistance in Streptococcus pneumoniae has increased worldwide, making fluoroquinolones an alternative therapeutic option. Fluoroquinolones inhibit the type II DNA topoisomerases (topoisomerase IV and gyrase). In this study we have evaluated the in vivo activity of seconeolitsine, an inhibitor of topoisomerase I. Levofloxacin [...] Read more.

Antibiotic resistance in Streptococcus pneumoniae has increased worldwide, making fluoroquinolones an alternative therapeutic option. Fluoroquinolones inhibit the type II DNA topoisomerases (topoisomerase IV and gyrase). In this study we have evaluated the in vivo activity of seconeolitsine, an inhibitor of topoisomerase I. Levofloxacin (12.5 to 50 mg/kg) or seconeolitsine (5 to 40 mg/kg) were administered every 12 h during two days in mice infected with a serotype 8-resistant strain. At 48 h, a 70% protection was obtained with seconeolitsine (40 mg/kg; p < 0.001). However, survival with levofloxacin was 20%, regardless of the dose. In addition, seconeolitsine decreased bacteremia efficiently. Levofloxacin had higher levels in serum than seconeolitsine (Cmax of 14.7 vs. 1.6; p < 0.01) and higher values of area under the serum concentration-time curve (AUC_0-12h of 17.3 vs. 5; p < 0.01). However, seconeolitsine showed higher levels of time to peak concentration and elimination half-life. This is consistent with the higher binding of seconeolitsine to plasma proteins (40% and 80% when used at 1 µg/mL and 50 µg/mL, respectively) in comparison to levofloxacin (12% at 5 µg/mL and 33% at 50 µg/mL). Our results suggest that seconeolitsine would be a promising therapeutic alternative against pneumococcal isolates with high fluoroquinolone resistance levels. Full article

(This article belongs to the Special Issue Research and Development of Antibiotics)

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Review

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Open AccessReview

Potential Environmental and Human Health Risks Caused by Antibiotic-Resistant Bacteria (ARB), Antibiotic Resistance Genes (ARGs) and Emerging Contaminants (ECs) from Municipal Solid Waste (MSW) Landfill

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Kavindra Kumar Kesari

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and

Antibiotics 2021, 10(4), 374; https://doi.org/10.3390/antibiotics10040374 - 01 Apr 2021

Cited by 53 | Viewed by 9303

Abstract

The disposal of municipal solid waste (MSW) directly at landfills or open dump areas, without segregation and treatment, is a significant concern due to its hazardous contents of antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARGs), and metal resistance genes (MGEs). The released leachate [...] Read more.

The disposal of municipal solid waste (MSW) directly at landfills or open dump areas, without segregation and treatment, is a significant concern due to its hazardous contents of antibiotic-resistant bacteria (ARB), antibiotic resistance genes (ARGs), and metal resistance genes (MGEs). The released leachate from landfills greatly effects the soil physicochemical, biological, and groundwater properties associated with agricultural activity and human health. The abundance of ARB, ARGs, and MGEs have been reported worldwide, including MSW landfill sites, animal husbandry, wastewater, groundwater, soil, and aerosol. This review elucidates the occurrence and abundance of ARB, ARGs, and MRGs, which are regarded as emerging contaminants (ECs). Recently, ECs have received global attention because of their prevalence in leachate as a substantial threat to environmental and public health, including an economic burden for developing nations. The present review exclusively discusses the demands to develop a novel eco-friendly management strategy to combat these global issues. This review also gives an intrinsic discussion about the insights of different aspects of environmental and public health concerns caused due to massive leachate generation, the abundance of antibiotics resistance (AR), and the effects of released leachate on the various environmental reservoirs and human health. Furthermore, the current review throws light on the source and fate of different ECs of landfill leachate and their possible impact on the nearby environments (groundwater, surface water, and soil) affecting human health. The present review strongly suggests the demand for future research focuses on the advancement of the removal efficiency of contaminants with the improvement of relevant landfill management to reduce the potential effects of disposable waste. We propose the necessity of the identification and monitoring of potential environmental and human health risks associated with landfill leachate contaminants. Full article

(This article belongs to the Special Issue Research and Development of Antibiotics)

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Open AccessReview

Essential Oils as Antimicrobials in Crop Protection

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and

Antibiotics 2021, 10(1), 34; https://doi.org/10.3390/antibiotics10010034 - 01 Jan 2021

Cited by 34 | Viewed by 4798

Abstract

At present, organic crops have reached an important boom in a society increasingly interested in the conservation of the environment and sustainability. It is evident that a part of the population in the Western world focuses their concern on how to obtain our [...] Read more.

At present, organic crops have reached an important boom in a society increasingly interested in the conservation of the environment and sustainability. It is evident that a part of the population in the Western world focuses their concern on how to obtain our food and on doing it in a way that is as respectful as possible with the environment. In this review, we present a compilation of the work carried out with the use of essential oils as an alternative in the fight against different bacteria and fungi that attack crops and related products. Given the collected works, the efficacy of essential oils for their use as pesticides for agricultural use is evident. Full article

(This article belongs to the Special Issue Research and Development of Antibiotics)

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Other

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Open AccessProject Report

Antibiotic Biosynthesis Pathways from Endophytic Streptomyces SUK 48 through Metabolomics and Genomics Approaches

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Syarul Nataqain Baharum

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Nuraziemah Ahmad

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Fazren Azmi

Antibiotics 2021, 10(8), 969; https://doi.org/10.3390/antibiotics10080969 - 12 Aug 2021

Cited by 3 | Viewed by 2189

Abstract

Streptomyces sp. has been known to be a major antibiotic producer since the 1940s. As the number of cases related to resistance pathogens infection increases yearly, discovering the biosynthesis pathways of antibiotic has become important. In this study, we present the streamline of [...] Read more.

Streptomyces sp. has been known to be a major antibiotic producer since the 1940s. As the number of cases related to resistance pathogens infection increases yearly, discovering the biosynthesis pathways of antibiotic has become important. In this study, we present the streamline of a project report summary; the genome data and metabolome data of newly isolated Streptomyces SUK 48 strain are also analyzed. The antibacterial activity of its crude extract is also determined. To obtain genome data, the genomic DNA of SUK 48 was extracted using a commercial kit (Promega) and sent for sequencing (Pac Biosciences technology platform, Menlo Park, CA, USA). The raw data were assembled and polished using Hierarchical Genome Assembly Process 4.0 (HGAP 4.0). The assembled data were structurally predicted using tRNAscan-SE and rnammer. Then, the data were analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG) database and antiSMASH analysis. Meanwhile, the metabolite profile of SUK 48 was determined using liquid chromatography-mass spectrophotometry (LC-MS) for both negative and positive modes. The results showed that the presence of kanamycin and gentamicin, as well as the other 11 antibiotics. Nevertheless, the biosynthesis pathways of aurantioclavine were also found. The cytotoxicity activity showed IC50 value was at 0.35 ± 1.35 mg/mL on the cell viability of HEK 293. In conclusion, Streptomyces sp. SUK 48 has proven to be a non-toxic antibiotic producer such as auranticlavine and gentamicin. Full article

(This article belongs to the Special Issue Research and Development of Antibiotics)

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