scholarly journals Brevibacillin 2V, a Novel Antimicrobial Lipopeptide With an Exceptionally Low Hemolytic Activity

2021 ◽  
Vol 12 ◽  
Author(s):  
Xinghong Zhao ◽  
Xiaoqi Wang ◽  
Rhythm Shukla ◽  
Raj Kumar ◽  
Markus Weingarth ◽  
...  
Keyword(s):  
Amino Acids ◽  
Total Synthesis ◽  
Hemolytic Activity ◽  
Bacterial Pathogens ◽  
Penicillin G ◽  
Antibiotic Resistant ◽  
Antibiotic Development ◽  
Brevibacillus Laterosporus ◽  
Strong Antimicrobial Activity

Bacterial non-ribosomally produced peptides (NRPs) form a rich source of antibiotics, including more than 20 of these antibiotics that are used in the clinic, such as penicillin G, colistin, vancomycin, and chloramphenicol. Here we report the identification, purification, and characterization of a novel NRP, i.e., brevibacillin 2V (lipo-tridecapeptide), from Brevibacillus laterosporus DSM 25. Brevibacillin 2V has a strong antimicrobial activity against Gram-positive bacterial pathogens (minimum inhibitory concentration = 2 mg/L), including difficult-to-treat antibiotic-resistant Enterococcus faecium, Enterococcus faecalis, and Staphylococcus aureus. Notably, brevibacillin 2V has a much lower hemolytic activity (HC50 > 128 mg/L) and cytotoxicity (CC50 = 45.49 ± 0.24 mg/L) to eukaryotic cells than previously reported NRPs of the lipo-tridecapeptide family, including other brevibacillins, which makes it a promising candidate for antibiotic development. In addition, our results demonstrate that brevibacillins display a synergistic action with established antibiotics against Gram-negative bacterial pathogens. Probably due to the presence of non-canonical amino acids and D-amino acids, brevibacillin 2V showed good stability in human plasma. Thus, we identified and characterized a novel and promising antimicrobial candidate (brevibacillin 2V) with low hemolytic activity and cytotoxicity, which can be used either on its own or as a template for further total synthesis and modification.

scholarly journals Brevibacillin 2V, a novel antimicrobial lipopeptide with an exceptional low hemolytic activity

2021 ◽  
Author(s):  
Xinghong Zhao ◽  
Xiaoqi Wang ◽  
Rhythm Shukla ◽  
Raj Kumar ◽  
Markus Weingarth ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Hemolytic Activity ◽  
Bacterial Pathogens ◽  
Penicillin G ◽  
Promising Candidate ◽  
Antibiotic Resistant ◽  
Antibiotic Development ◽  
Brevibacillus Laterosporus ◽  
Strong Antimicrobial Activity

AbstractBacterial non-ribosomally produced peptides (NRPs) form a rich source of antibiotics, including more than twenty of these antibiotics that are used in the clinic, such as penicillin G, colistin, vancomycin, and chloramphenicol. Here we report the identification, purification, and characterization of a novel NRP, i.e., brevibacillin 2V, from Brevibacillus laterosporus DSM 25. Brevibacillin 2V has strong antimicrobial activity against Gram-positive bacterial pathogens, including difficult-to-treat antibiotic-resistant Enterococcus faecium, Enterococcus faecalis, and Staphylococcus aureus. Notably, brevibacillin 2V has a much lower hemolytic activity to eukaryotic cells than previously reported NRPs of the lipo-tridecapeptide family, including other brevibacillins, which makes it a promising candidate for antibiotic development. In addition, our results demonstrate that brevibacillins display synergistic action with established antibiotics against Gram-negative bacterial pathogens. Thus, we identified and characterized a novel and promising antibiotic candidate (brevibacillin 2V) with a low hemolytic activity, which can be used either on its own or as a template for further total synthesis and modification.

Post-proline endopeptidase, further characterization of the enzyme from pig kidneys

1984 ◽  
Vol 49 (8) ◽  
pp. 1846-1853 ◽  
Author(s):  
Karel Hauzer ◽  
Tomislav Barth ◽  
Linda Servítová ◽  
Karel Jošt
Keyword(s):  
Amino Acids ◽  
Aspartic Acid ◽  
Ion Exchange Chromatography ◽  
Exchange Chromatography ◽  
Relative Molecular Mass ◽  
Enzyme Molecule ◽  
Thiol Compounds ◽  
Modified Method ◽  
N Terminus

A post-proline endopeptidase (EC 3.4.21.26) was isolated from pig kidneys using a modified method described earlier. The enzyme was further purified by ion exchange chromatography on DEAE-Sephacel. The final product contained about 95% of post-proline endopeptidase. The enzyme molecule consisted of one peptide chain with a relative molecular mass of 65 600 to 70 000, containing a large proportion of acidic and alifatic amino acids (glutamic acid, aspartic acid and leucine) and the N-terminus was formed by aspartic acid or asparagine. In order to prevent losses of enzyme activity, thiol compounds has to be added.

Total synthesis and structural characterization of caveolin‐1

2021 ◽  
Author(s):  
Hironobu Hojo ◽  
Toshiki Takei ◽  
Yuya Asahina ◽  
Nobuaki Okumura ◽  
Toshifumi Takao ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Structural Characterization ◽  
Caveolin 1

scholarly journals Characterization of CRISPR Spacer and Protospacer Sequences in Paenibacillus larvae and Its Bacteriophages

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 459
Author(s):  
Casey Stamereilers ◽  
Simon Wong ◽  
Philippos K. Tsourkas
Keyword(s):  
Comparative Studies ◽  
Point Mutations ◽  
Paenibacillus Larvae ◽  
Bacterial Disease ◽  
American Foulbrood ◽  
Antibiotic Resistant ◽  
Future Studies ◽  
Complete Genomes ◽  
Point Of Reference

The bacterium Paenibacillus larvae is the causative agent of American foulbrood, the most devastating bacterial disease of honeybees. Because P. larvae is antibiotic resistant, phages that infect it are currently used as alternative treatments. However, the acquisition by P. larvae of CRISPR spacer sequences from the phages could be an obstacle to treatment efforts. We searched nine complete genomes of P. larvae strains and identified 714 CRISPR spacer sequences, of which 384 are unique. Of the four epidemiologically important P. larvae strains, three of these have fewer than 20 spacers, while one strain has over 150 spacers. Of the 384 unique spacers, 18 are found as protospacers in the genomes of 49 currently sequenced P. larvae phages. One P. larvae strain does not have any protospacers found in phages, while another has eight. Protospacer distribution in the phages is uneven, with two phages having up to four protospacers, while a third of phages have none. Some phages lack protospacers found in closely related phages due to point mutations, indicating a possible escape mechanism. This study serve a point of reference for future studies on the CRISPR-Cas system in P. larvae as well as for comparative studies of other phage–host systems.

scholarly journals Avoided motifs: short amino acid strings missing from protein datasets

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Pablo Mier ◽  
Miguel A. Andrade-Navarro
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Protein Function ◽  
Large Protein ◽  
New Approach ◽  
Cellular Context ◽  
Human Proteins ◽  
Context Specific ◽  
Protein Datasets

Abstract According to the amino acid composition of natural proteins, it could be expected that all possible sequences of three or four amino acids will occur at least once in large protein datasets purely by chance. However, in some species or cellular context, specific short amino acid motifs are missing due to unknown reasons. We describe these as Avoided Motifs, short amino acid combinations missing from biological sequences. Here we identify 209 human and 154 bacterial Avoided Motifs of length four amino acids, and discuss their possible functionality according to their presence in other species. Furthermore, we determine two Avoided Motifs of length three amino acids in human proteins specifically located in the cytoplasm, and two more in secreted proteins. Our results support the hypothesis that the characterization of Avoided Motifs in particular contexts can provide us with information about functional motifs, pointing to a new approach in the use of molecular sequences for the discovery of protein function.

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