scholarly journals Evaluation of the Toxicity of the Ethanol Extract 70% of the Bark of Terminalia macroptera (Combretaceae) on Whistar Rats

2019 ◽  
pp. 1-17
Author(s):  
Traore Youssouf ◽  
Koné Monon ◽  
Ouattara Abou ◽  
Bahi Calix ◽  
Nathalie Kouadio Guessennd ◽  
...  
Keyword(s):  
Acute Toxicity ◽  
Hematological Parameters ◽  
Infectious Agent ◽  
Ethanol Extract ◽  
The Body ◽  
Resistant Bacteria ◽  
Real Problem ◽  
Toxic Substances ◽  
Antibiotic Resistant ◽  
Conventional Antibiotics

Nowadays, many medicinal plants have proved effective in combating the phenomenon of bacterial multi-resistance against conventional antibiotics. However, the use of these plants, traditionally is done without precise doses. And this inaccuracy of dose is a real problem of traditional medicine. Thus prospecting for empirically administered plant extract requires dosage monitoring to avoid the risk of a fatal therapeutic accident. It is in this context that the study of the toxicity of Terminalia macroptera which presents itself as an anti-infectious agent, capable of overcoming certain strains of antibiotic-resistant bacteria has been initiated. The objective of this study is to evaluate the toxicity of 70% ethanol extract of T.macroptera in rats and to deduce its safety. With regard to the evaluation of the toxicity, rats were used whose mass varies between 100 and 170 grams. Then, using OECD Guideline 425, (2006), acute toxicity was achieved. Then the 100, 300 and 500 mg / kg bm doses were used in sub-acute toxicity to evaluate biochemical and hematological parameters. The results show an LD50> 5000 mg / kg bm. Therefore, according to the OECD classification, the hydroethanolic extract belongs to category 5, non-toxic substances. Also, the biochemical and hematological results revealed that the extract did not change at any time at P <0.05, biochemical marker levels (UREE, ASAT, ALAT, CK and LDH), reflecting vital organs of the body. So the extract would have no effect on the heart, liver and kidneys. 70% ethanol extract of T. macroptera would be safe for use as a drug and therefore could contribute to the production of Traditionally Enhanced Medicines (MTAs).

scholarly journals The Potential of Human Peptide LL-37 as an Antimicrobial and Anti-Biofilm Agent

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 650
Author(s):  
Kylen E. Ridyard ◽  
Joerg Overhage
Keyword(s):  
Bacterial Infections ◽  
Antimicrobial Properties ◽  
Cross Resistance ◽  
Resistant Bacteria ◽  
Peptide Antibiotic ◽  
Adaptive Responses ◽  
Antibiotic Resistant ◽  
Structural Modifications ◽  
Immobilization Techniques ◽  
Conventional Antibiotics

The rise in antimicrobial resistant bacteria threatens the current methods utilized to treat bacterial infections. The development of novel therapeutic agents is crucial in avoiding a post-antibiotic era and the associated deaths from antibiotic resistant pathogens. The human antimicrobial peptide LL-37 has been considered as a potential alternative to conventional antibiotics as it displays broad spectrum antibacterial and anti-biofilm activities as well as immunomodulatory functions. While LL-37 has shown promising results, it has yet to receive regulatory approval as a peptide antibiotic. Despite the strong antimicrobial properties, LL-37 has several limitations including high cost, lower activity in physiological environments, susceptibility to proteolytic degradation, and high toxicity to human cells. This review will discuss the challenges associated with making LL-37 into a viable antibiotic treatment option, with a focus on antimicrobial resistance and cross-resistance as well as adaptive responses to sub-inhibitory concentrations of the peptide. The possible methods to overcome these challenges, including immobilization techniques, LL-37 delivery systems, the development of LL-37 derivatives, and synergistic combinations will also be considered. Herein, we describe how combination therapy and structural modifications to the sequence, helicity, hydrophobicity, charge, and configuration of LL-37 could optimize the antimicrobial and anti-biofilm activities of LL-37 for future clinical use.

scholarly journals Design, Overproduction and Purification of the Chimeric Phage Lysin MLTphg Fighting against Staphylococcus aureus

Processes ◽  
2020 ◽  
Vol 8 (12) ◽  
pp. 1587
Author(s):  
Feng Wang ◽  
Xiaohang Liu ◽  
Zhengyu Deng ◽  
Yao Zhang ◽  
Xinyu Ji ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
E Coli ◽  
Conventional Antibiotics ◽  
Phage Lysin ◽  
Shed Light

With the increasing spread of multidrug-resistant bacterial pathogens, it is of great importance to develop alternatives to conventional antibiotics. Here, we report the generation of a chimeric phage lysin, MLTphg, which was assembled by joining the lysins derived from Meiothermus bacteriophage MMP7 and Thermus bacteriophage TSP4 with a flexible linker via chimeolysin engineering. As a potential antimicrobial agent, MLTphg can be obtained by overproduction in Escherichia coli BL21(DE3) cells and the following Ni-affinity chromatography. Finally, we recovered about 40 ± 1.9 mg of MLTphg from 1 L of the host E. coli BL21(DE3) culture. The purified MLTphg showed peak activity against Staphylococcus aureus ATCC6538 between 35 and 40 °C, and maintained approximately 44.5 ± 2.1% activity at room temperature (25 °C). Moreover, as a produced chimera, it exhibited considerably improved bactericidal activity against Staphylococcus aureus (2.9 ± 0.1 log10 reduction was observed upon 40 nM MLTphg treatment at 37 °C for 30 min) and also a group of antibiotic-resistant bacteria compared to its parental lysins, TSPphg and MMPphg. In the current age of growing antibiotic resistance, our results provide an engineering basis for developing phage lysins as novel antimicrobial agents and shed light on bacteriophage-based strategies to tackle bacterial infections.

scholarly journals IOX1 activity as sepsis therapy and an antibiotic against multidrug-resistant bacteria

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Su Jin Lee ◽  
Jueng Soo You ◽  
Amal Gharbi ◽  
Yong Joo Kim ◽  
Mi Suk Lee ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Bacterial Sepsis ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Carbapenem Resistant ◽  
Sepsis Therapy ◽  
Inflammatory State ◽  
Conventional Antibiotics ◽  
Lysine Demethylase

AbstractSepsis is caused by organ dysfunction initiated by an unrestrained host immune response to infection. The emergence of antibiotic-resistant bacteria has rapidly increased in the last decades and has stimulated a firm research platform to combat infections caused by antibiotic-resistant bacteria that cannot be eradicated with conventional antibiotics. Strategies like epigenetic regulators such as lysine demethylase (Kdm) has received attention as a new target. Thus, we sought to investigate the epigenetic mechanisms in sepsis pathophysiology with the aim of discovering new concepts for treatment. A transcriptome analysis of dendritic cells during their inflammatory state identified Kdm as a critical molecule in sepsis regulation. Next, 8-hydroxyquinoline-5-carboxylic acid (IOX1) ability to control endotoxemia induced by Lipopolysaccharide and bacterial sepsis was demonstrated. IOX1 has been shown to regulate endotoxemia and sepsis caused by Escherichia coli and carbapenem-resistant Acinetobacter baumannii and has also contributed to the suppression of multidrug-resistant bacterial growth through the inhibition of DNA Gyrase. These findings show that IOX1 could be a component agent against bacterial sepsis by functioning as a broad-spectrum antibiotic with dual effects.

scholarly journals Inorganic nanohybrids combat antibiotic-resistant bacteria hiding within human macrophages

Nanoscale ◽  
2021 ◽  
Author(s):  
Martin T. Matter ◽  
Meagan Doppegieter ◽  
Alexander Gogos ◽  
Kerda Keevend ◽  
Qun Ren ◽  
...  
Keyword(s):  
Human Cells ◽  
Resistant Bacteria ◽  
Bacterial Survival ◽  
Antibiotic Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Human Macrophages ◽  
Conventional Antibiotics

Ceria/bioglass nanohybrids significantly reduce bacterial survival inside human cells without harming the latter and overcome major shortcomings of conventional antibiotics.

scholarly journals Quorum-sensing blockade as a strategy for enhancing host defences against bacterial pathogens

2007 ◽  
Vol 362 (1483) ◽  
pp. 1213-1222 ◽  
Author(s):  
Thomas Bjarnsholt ◽  
Michael Givskov
Keyword(s):  
Quorum Sensing ◽  
Drug Target ◽  
Immune Modulation ◽  
Resistant Bacteria ◽  
Signal Molecules ◽  
Antibiotic Resistant ◽  
Bacterial Pathogenicity ◽  
Extracellular Signal ◽  
Conventional Antibiotics ◽  
Antimicrobial Treatments

Conventional antibiotics target the growth and the basal life processes of bacteria leading to growth arrest and cell death. The selective force that is inherently linked to this mode of action eventually selects out antibiotic-resistant variants. The most obvious alternative to antibiotic-mediated killing or growth inhibition would be to attenuate the bacteria with respect to pathogenicity. The realization that Pseudomonas aeruginosa , and a number of other pathogens, controls much of their virulence arsenal by means of extracellular signal molecules in a process denoted quorum sensing (QS) gave rise to a new ‘drug target rush’. Recently, QS has been shown to be involved in the development of tolerance to various antimicrobial treatments and immune modulation. The regulation of virulence via QS confers a strategic advantage over host defences. Consequently, a drug capable of blocking QS is likely to increase the susceptibility of the infecting organism to host defences and its clearance from the host. The use of QS signal blockers to attenuate bacterial pathogenicity, rather than bacterial growth, is therefore highly attractive, particularly with respect to the emergence of multi-antibiotic resistant bacteria.

scholarly journals Proteomic Characterization of Antibiotic Resistance, and Production of Antimicrobial and Virulence Factors in Streptococcus Species Associated with Bovine Mastitis. Could Enzybiotics Represent Novel Therapeutic Agents Against These Pathogens?

Antibiotics ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 302 ◽  
Author(s):  
Ana G. Abril ◽  
Mónica Carrera ◽  
Karola Böhme ◽  
Jorge Barros-Velázquez ◽  
José-Luis R. Rama ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Virulence Factors ◽  
Research Work ◽  
Bovine Mastitis ◽  
Mass Spectrometry Analysis ◽  
Resistant Bacteria ◽  
Toxic Substances ◽  
Antibiotic Resistant ◽  
Spectrometry Analysis ◽  
Species Specific

Streptococcus spp. are major mastitis pathogens present in dairy products, which produce a variety of virulence factors that are involved in streptococcal pathogenicity. These include neuraminidase, pyrogenic exotoxin, and M protein, and in addition they might produce bacteriocins and antibiotic-resistance proteins. Unjustifiable misuse of antimicrobials has led to an increase in antibiotic-resistant bacteria present in foodstuffs. Identification of the mastitis-causing bacterial strain, as well as determining its antibiotic resistance and sensitivity is crucial for effective therapy. The present work focused on the LC–ESI–MS/MS (liquid chromatography–electrospray ionization tandem mass spectrometry) analysis of tryptic digestion peptides from mastitis-causing Streptococcus spp. isolated from milk. A total of 2706 non-redundant peptides belonging to 2510 proteins was identified and analyzed. Among them, 168 peptides were determined, representing proteins that act as virulence factors, toxins, anti-toxins, provide resistance to antibiotics that are associated with the production of lantibiotic-related compounds, or play a role in the resistance to toxic substances. Protein comparisons with the NCBI database allowed the identification of 134 peptides as specific to Streptococcus spp., while two peptides (EATGNQNISPNLTISNAQLNLEDKNK and DLWC*NM*IIAAK) were found to be species-specific to Streptococcus dysgalactiae. This proteomic repository might be useful for further studies and research work, as well as for the development of new therapeutics for the mastitis-causing Streptococcus strains.

scholarly journals Synanthropic spiders, including the global invasive noble false widow Steatoda nobilis, are reservoirs for medically important and antibiotic resistant bacteria

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
John P. Dunbar ◽  
Neyaz A. Khan ◽  
Cathy L. Abberton ◽  
Pearce Brosnan ◽  
Jennifer Murphy ◽  
...  
Keyword(s):  
Pseudomonas Putida ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
The Body ◽  
Resistant Bacteria ◽  
Pathogenic Potential ◽  
Antibiotic Resistant ◽  
Opportunistic Bacteria ◽  
Staphylococcus Capitis

AbstractThe false widow spider Steatoda nobilis is associated with bites which develop bacterial infections that are sometimes unresponsive to antibiotics. These could be secondary infections derived from opportunistic bacteria on the skin or infections directly vectored by the spider. In this study, we investigated whether it is plausible for S. nobilis and other synanthropic European spiders to vector bacteria during a bite, by seeking to identify bacteria with pathogenic potential on the spiders. 11 genera of bacteria were identified through 16S rRNA sequencing from the body surfaces and chelicerae of S. nobilis, and two native spiders: Amaurobius similis and Eratigena atrica. Out of 22 bacterial species isolated from S. nobilis, 12 were related to human pathogenicity among which Staphylococcus epidermidis, Kluyvera intermedia, Rothia mucilaginosa and Pseudomonas putida are recognized as class 2 pathogens. The isolates varied in their antibiotic susceptibility: Pseudomonas putida, Staphylococcus capitis and Staphylococcus edaphicus showed the highest extent of resistance, to three antibiotics in total. On the other hand, all bacteria recovered from S. nobilis were susceptible to ciprofloxacin. Our study demonstrates that S. nobilis does carry opportunistic pathogenic bacteria on its body surfaces and chelicerae. Therefore, some post-bite infections could be the result of vector-borne bacterial zoonoses that may be antibiotic resistant.

scholarly journals Boosting Synergistic Effects of Short Antimicrobial Peptides With Conventional Antibiotics Against Resistant Bacteria

2021 ◽  
Vol 12 ◽  
Author(s):  
Chih-Lung Wu ◽  
Kuang-Li Peng ◽  
Bak-Sau Yip ◽  
Ya-Han Chih ◽  
Jya-Wei Cheng
Keyword(s):  
Antimicrobial Peptides ◽  
Synergistic Effects ◽  
Antibacterial Activities ◽  
Resistant Bacteria ◽  
Bacterial Strains ◽  
Antibiotic Resistant ◽  
C Terminus ◽  
Global Spread ◽  
Synergistic Mechanism ◽  
Conventional Antibiotics

The global spread of antibiotic-resistant infections has meant that there is an urgent need to develop new antimicrobial alternatives. In this study, we developed a strategy to boost and/or synergize the activity of conventional antibiotics by combination with antimicrobial peptides tagged with the bulky non-natural amino acid β-naphthylalanine (Nal) to their N- or C-terminus. A checkerboard method was used to evaluate synergistic effects of the parent peptide and the Nal-tagged peptides. Moreover, boron-dipyrro-methene labeled vancomycin was used to characterize the synergistic mechanism of action between the peptides and vancomycin on the bacterial strains. These Nal-tagged antimicrobial peptides also reduced the antibiotic-induced release of lipopolysaccharide from Gram-negative bacteria by more than 99.95%. Our results demonstrate that Nal-tagged peptides could help in developing antimicrobial peptides that not only have enhanced antibacterial activities but also increase the synergistic effects with conventional antibiotics against antibiotic-resistant bacteria.

scholarly journals Evaluation of Acute Toxicity of Ethanol Extract of Pirdot Leaf (Saurauia vulcani Korth.) in Rats

2020 ◽  
Vol 3 (2) ◽  
pp. 13-18
Author(s):  
Nerly Juli Pranita Simanjuntak ◽  
Rosidah ◽  
Yuandani
Keyword(s):  
Acute Toxicity ◽  
Blood Cells ◽  
Hematological Parameters ◽  
White Blood Cells ◽  
Ethanolic Extract ◽  
Ethanol Extract ◽  
Female Rats ◽  
Control Group ◽  
Mean Corpuscular Hemoglobin ◽  
Corpuscular Hemoglobin

Traditionally pirdot leaves are used to treat various diseases. The purpose of this study was to determine determine the potential for acute toxicity of ethanolic extract of pirdot leaf (Saurauia vulcani Korth.) with value LD50 and hematological Parameters in rats. The acute toxicity of ethanolic extract of pirdot leaf was evaluated by OECD guidelines. The number of animals used in this research were 15 female rats. The control group was given Na CMC 0.5%, the treatment groups were given ethanolic extract of pirdot leaves with doses 2000 and 5000 mg/kg bw. The results showed that ethanolic extract of pirdot leaves with doses of 2000 and 5000 mg/kg bw did not show any toxicity signs. There was no mortality was observe. The ethanolic extract of pirdot leaves did not cause any changes in hematological parameters, these include red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), platelet, white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, and basophils levels as compared to normal control (P>0.05). It was estimated that LD50 of ethanolic extract of pirdot leaves was higher than 5000 mg/kg bw and the extract were practically non-toxic. The ethanolic extract of pirdot leaves did not cause any toxic effect on hematological parameters.

scholarly journals An Updated Review on the Synthesis and Antibacterial Activity of Molecular Hybrids and Conjugates Bearing Imidazole Moiety

Molecules ◽  
2020 ◽  
Vol 25 (21) ◽  
pp. 5133 ◽  
Author(s):  
Renzo Rossi ◽  
Maurizio Ciofalo
Keyword(s):  
Bacterial Resistance ◽  
Antibacterial Properties ◽  
Resistant Bacteria ◽  
Antibiotic Resistant ◽  
Major Health ◽  
Serious Infections ◽  
Molecular Hybrids ◽  
Covalently Linked ◽  
Conventional Antibiotics ◽  
Eskape Pathogens

The rapid growth of serious infections caused by antibiotic resistant bacteria, especially the nosocomial ESKAPE pathogens, has been acknowledged by Governments and scientists and is one of the world’s major health problems. Various strategies have been and are currently investigated and developed to reduce and/or delay the bacterial resistance. One of these strategies regards the design and development of antimicrobial hybrids and conjugates. This unprecedented critical review, in which our continuing interest in the synthesis and evaluation of the bioactivity of imidazole derivatives is testified, aims to summarise and comment on the results obtained from the end of the 1900s until February 2020 in studies conducted by numerous international research groups on the synthesis and evaluation of the antibacterial properties of imidazole-based molecular hybrids and conjugates in which the pharmacophoric constituents of these compounds are directly covalently linked or connected through a linker or spacer. In this review, significant attention was paid to summarise the strategies used to overcome the antibiotic resistance of pathogens whose infections are difficult to treat with conventional antibiotics. However, it does not include literature data on the synthesis and evaluation of the bioactivity of hybrids and conjugates in which an imidazole moiety is fused with a carbo- or heterocyclic subunit.

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