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Structure-Activity Relationship and Mode of Action of a Frog Secreted Antibacterial Peptide B1CTcu5 Using Synthetically and Modularly Modified or Deleted (SMMD) Peptides.

Abraham P, Sundaram A, R A, V R, George S, Kumar KS - PLoS ONE (2015)

Bottom Line: Its higher activity was well correlated with the improved inner membrane permeabilisation capacity.The bactericidal potency of the D-peptide (DB1CTcu5) helped to rule out the stereospecific interaction with the bacterial membrane.Our data suggests that both the C and N-terminal regions are necessary for bactericidal activity, even though the active core region is located near the N-terminal of B1CTcu5.

View Article: PubMed Central - PubMed

Affiliation: Chemical Biology Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.

ABSTRACT
All life forms are equipped with rapidly acting, evolutionally conserved components of an innate immune defense system that consists of a group of unique and diverse molecules known as host defense peptides (HDPs). A Systematic and Modular Modification and Deletion (SMMD) approach was followed to analyse the structural requirement of B1CTcu5, a brevinin antibacterial peptide amide identified from the skin secretion of frog Clinotarsus curtipes, India, to show antibacterial activity and to explore the active core region. Seventeen SMMD-B1CTcu5 analogs were designed and synthesised by C and N-terminal amino acid substitution or deletion. Enhancement in cationicity by N-terminal Lys/Arg substitution or hydrophobicity by Trp substitution produced no drastic change in bactericidal nature against selected bacterial strains except S. aureus. But the sequential removal of N-terminal amino acids had a negative effect on bactericidal potency. Analog B1CTcu5-LIAG obtained by the removal of four N-terminal amino acids displayed bactericidal effect comparable to, or in excess of, the parent peptide with reduced hemolytic character. Its higher activity was well correlated with the improved inner membrane permeabilisation capacity. This region may act as the active core of B1CTcu5. Presence of C-terminal disulphide bond was not a necessary condition to display antibacterial activity but helped to promote hemolytic nature. Removal of the C-terminal rana box region drastically reduced antibacterial and hemolytic activity of the peptide, showing that this region is important for membrane targeting. The bactericidal potency of the D-peptide (DB1CTcu5) helped to rule out the stereospecific interaction with the bacterial membrane. Our data suggests that both the C and N-terminal regions are necessary for bactericidal activity, even though the active core region is located near the N-terminal of B1CTcu5. A judicious modification at the N-terminal region may produce a short SMMD analog with enhanced bactericidal activity and low toxicity against eukaryotic cells.

No MeSH data available.


Related in: MedlinePlus

Effect of peptides against biofilm formation by S. aureus strains.Biofilm formed by S. aureus at 12 h were treated with 100μg/ml of peptides for 12 h and the biofilm formation was determined by measuring the absorbance at 570 nm.
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pone.0124210.g002: Effect of peptides against biofilm formation by S. aureus strains.Biofilm formed by S. aureus at 12 h were treated with 100μg/ml of peptides for 12 h and the biofilm formation was determined by measuring the absorbance at 570 nm.

Mentions: The antibiofilm activity of the potent peptides was as evaluated on S. aureus strains (same strain used for antibacterial analysis) and the results are presented in Fig 2. B1CTcu5K exhibited 54.3% biofilm inhibition activity while the parent peptide B1CTcu5 showed only 18.6% compared to untreated bacterial cells. The percentage inhibition showed by the SMMD analogs DB1CTcu5, B1CTcu5W, B1CTcu5R, B1CTcu5H and B1CTcu5-LIAG are 34.25%, 13%, 31.21%, 32.5% and 25% respectively.


Structure-Activity Relationship and Mode of Action of a Frog Secreted Antibacterial Peptide B1CTcu5 Using Synthetically and Modularly Modified or Deleted (SMMD) Peptides.

Abraham P, Sundaram A, R A, V R, George S, Kumar KS - PLoS ONE (2015)

Effect of peptides against biofilm formation by S. aureus strains.Biofilm formed by S. aureus at 12 h were treated with 100μg/ml of peptides for 12 h and the biofilm formation was determined by measuring the absorbance at 570 nm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4440778&req=5

pone.0124210.g002: Effect of peptides against biofilm formation by S. aureus strains.Biofilm formed by S. aureus at 12 h were treated with 100μg/ml of peptides for 12 h and the biofilm formation was determined by measuring the absorbance at 570 nm.
Mentions: The antibiofilm activity of the potent peptides was as evaluated on S. aureus strains (same strain used for antibacterial analysis) and the results are presented in Fig 2. B1CTcu5K exhibited 54.3% biofilm inhibition activity while the parent peptide B1CTcu5 showed only 18.6% compared to untreated bacterial cells. The percentage inhibition showed by the SMMD analogs DB1CTcu5, B1CTcu5W, B1CTcu5R, B1CTcu5H and B1CTcu5-LIAG are 34.25%, 13%, 31.21%, 32.5% and 25% respectively.

Bottom Line: Its higher activity was well correlated with the improved inner membrane permeabilisation capacity.The bactericidal potency of the D-peptide (DB1CTcu5) helped to rule out the stereospecific interaction with the bacterial membrane.Our data suggests that both the C and N-terminal regions are necessary for bactericidal activity, even though the active core region is located near the N-terminal of B1CTcu5.

View Article: PubMed Central - PubMed

Affiliation: Chemical Biology Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India.

ABSTRACT
All life forms are equipped with rapidly acting, evolutionally conserved components of an innate immune defense system that consists of a group of unique and diverse molecules known as host defense peptides (HDPs). A Systematic and Modular Modification and Deletion (SMMD) approach was followed to analyse the structural requirement of B1CTcu5, a brevinin antibacterial peptide amide identified from the skin secretion of frog Clinotarsus curtipes, India, to show antibacterial activity and to explore the active core region. Seventeen SMMD-B1CTcu5 analogs were designed and synthesised by C and N-terminal amino acid substitution or deletion. Enhancement in cationicity by N-terminal Lys/Arg substitution or hydrophobicity by Trp substitution produced no drastic change in bactericidal nature against selected bacterial strains except S. aureus. But the sequential removal of N-terminal amino acids had a negative effect on bactericidal potency. Analog B1CTcu5-LIAG obtained by the removal of four N-terminal amino acids displayed bactericidal effect comparable to, or in excess of, the parent peptide with reduced hemolytic character. Its higher activity was well correlated with the improved inner membrane permeabilisation capacity. This region may act as the active core of B1CTcu5. Presence of C-terminal disulphide bond was not a necessary condition to display antibacterial activity but helped to promote hemolytic nature. Removal of the C-terminal rana box region drastically reduced antibacterial and hemolytic activity of the peptide, showing that this region is important for membrane targeting. The bactericidal potency of the D-peptide (DB1CTcu5) helped to rule out the stereospecific interaction with the bacterial membrane. Our data suggests that both the C and N-terminal regions are necessary for bactericidal activity, even though the active core region is located near the N-terminal of B1CTcu5. A judicious modification at the N-terminal region may produce a short SMMD analog with enhanced bactericidal activity and low toxicity against eukaryotic cells.

No MeSH data available.


Related in: MedlinePlus