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Antimicrobial Activity of Novel Synthetic Peptides Derived from Indolicidin and Ranalexin against Streptococcus pneumoniae.

Jindal HM, Le CF, Mohd Yusof MY, Velayuthan RD, Lee VS, Zain SM, Isa DM, Sekaran SD - PLoS ONE (2015)

Bottom Line: The cytotoxic effects of peptides were tested against human erythrocytes, WRL-68 normal liver cell line, and NL-20 normal lung cell line.The results revealed that none of the thirteen peptides have cytotoxic or hemolytic effects at their MIC values.RN7IN6 showed a strong affinity to target proteins; autolysin, pneumolysin, and pneumococcal surface protein A (PspA) based on rigid docking studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.

ABSTRACT
Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics in order to defeat multidrug-resistant bacteria such as Streptococcus pneumoniae. In this study, thirteen antimicrobial peptides were designed based on two natural peptides indolicidin and ranalexin. Our results revealed that four hybrid peptides RN7-IN10, RN7-IN9, RN7-IN8, and RN7-IN6 possess potent antibacterial activity against 30 pneumococcal clinical isolates (MIC 7.81-15.62µg/ml). These four hybrid peptides also showed broad spectrum antibacterial activity (7.81µg/ml) against S. aureus, methicillin resistant S. aureus (MRSA), and E. coli. Furthermore, the time killing assay results showed that the hybrid peptides were able to eliminate S. pneumoniae within less than one hour which is faster than the standard drugs erythromycin and ceftriaxone. The cytotoxic effects of peptides were tested against human erythrocytes, WRL-68 normal liver cell line, and NL-20 normal lung cell line. The results revealed that none of the thirteen peptides have cytotoxic or hemolytic effects at their MIC values. The in silico molecular docking study was carried out to investigate the binding properties of peptides with three pneumococcal virulent targets by Autodock Vina. RN7IN6 showed a strong affinity to target proteins; autolysin, pneumolysin, and pneumococcal surface protein A (PspA) based on rigid docking studies. Our results suggest that the hybrid peptides could be suitable candidates for antibacterial drug development.

No MeSH data available.


Related in: MedlinePlus

Time killing assay.Bactericidal kinetics of peptides at 1×MIC, bactericidal kinetics of indolicidin and its analogs against resistant and susceptible S. pneumoniae to ceftriaxone (CFX) and erythromycin (ERY) (A and B respectively). Bactericidal kinetics of hybrid peptides against resistant and susceptible S. pneumoniae (C and D). All the designed peptides showed stronger bactericidal activity than standard drugs at 1x MIC (with statistical significance using two-way analysis of variance. An asterisk (*) adjacent to peptide name indicates statistical analysis significance (P <0.0001).
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pone.0128532.g004: Time killing assay.Bactericidal kinetics of peptides at 1×MIC, bactericidal kinetics of indolicidin and its analogs against resistant and susceptible S. pneumoniae to ceftriaxone (CFX) and erythromycin (ERY) (A and B respectively). Bactericidal kinetics of hybrid peptides against resistant and susceptible S. pneumoniae (C and D). All the designed peptides showed stronger bactericidal activity than standard drugs at 1x MIC (with statistical significance using two-way analysis of variance. An asterisk (*) adjacent to peptide name indicates statistical analysis significance (P <0.0001).

Mentions: The bactericidal activity of peptides was assessed by evaluating the time course to kill suspensions of Streptococcus pneumoniae. Hybrid peptides showed rapid bactericidal kinetics in comparison with standard drugs erythromycin and ceftriaxone. RN7-IN10 was the most active peptide eliminating 106 CFU/ml of S. pneumoniae at 1×MIC over a period of 30 min. RN7-IN8 and RN7-IN7 took 120 min to completely eradicate 106 CFU/ml, whereas peptide RN7-IN9 was able to completely kill the bacteria within 150 min. RN7-IN6 had the slowest killing rate against S. pneumoniae, taking 240 min to kill the bacteria (Fig 4A and 4B). Indolicidin analogs IN1 and IN2 had slower killing kinetics than their parent peptide. They required 210 min to totally eliminate the bacteria, whereas indolicidin and IN3 took 150 min to kill 106 CFU/ml of pneumococcus. Standard drugs erythromycin and ceftriaxone eradicated susceptible pneumococcal isolate at 120 and 150 min respectively and failed to totally eliminate resistant strain up to 240 min of treatment (Fig 4C and 4D).


Antimicrobial Activity of Novel Synthetic Peptides Derived from Indolicidin and Ranalexin against Streptococcus pneumoniae.

Jindal HM, Le CF, Mohd Yusof MY, Velayuthan RD, Lee VS, Zain SM, Isa DM, Sekaran SD - PLoS ONE (2015)

Time killing assay.Bactericidal kinetics of peptides at 1×MIC, bactericidal kinetics of indolicidin and its analogs against resistant and susceptible S. pneumoniae to ceftriaxone (CFX) and erythromycin (ERY) (A and B respectively). Bactericidal kinetics of hybrid peptides against resistant and susceptible S. pneumoniae (C and D). All the designed peptides showed stronger bactericidal activity than standard drugs at 1x MIC (with statistical significance using two-way analysis of variance. An asterisk (*) adjacent to peptide name indicates statistical analysis significance (P <0.0001).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4457802&req=5

pone.0128532.g004: Time killing assay.Bactericidal kinetics of peptides at 1×MIC, bactericidal kinetics of indolicidin and its analogs against resistant and susceptible S. pneumoniae to ceftriaxone (CFX) and erythromycin (ERY) (A and B respectively). Bactericidal kinetics of hybrid peptides against resistant and susceptible S. pneumoniae (C and D). All the designed peptides showed stronger bactericidal activity than standard drugs at 1x MIC (with statistical significance using two-way analysis of variance. An asterisk (*) adjacent to peptide name indicates statistical analysis significance (P <0.0001).
Mentions: The bactericidal activity of peptides was assessed by evaluating the time course to kill suspensions of Streptococcus pneumoniae. Hybrid peptides showed rapid bactericidal kinetics in comparison with standard drugs erythromycin and ceftriaxone. RN7-IN10 was the most active peptide eliminating 106 CFU/ml of S. pneumoniae at 1×MIC over a period of 30 min. RN7-IN8 and RN7-IN7 took 120 min to completely eradicate 106 CFU/ml, whereas peptide RN7-IN9 was able to completely kill the bacteria within 150 min. RN7-IN6 had the slowest killing rate against S. pneumoniae, taking 240 min to kill the bacteria (Fig 4A and 4B). Indolicidin analogs IN1 and IN2 had slower killing kinetics than their parent peptide. They required 210 min to totally eliminate the bacteria, whereas indolicidin and IN3 took 150 min to kill 106 CFU/ml of pneumococcus. Standard drugs erythromycin and ceftriaxone eradicated susceptible pneumococcal isolate at 120 and 150 min respectively and failed to totally eliminate resistant strain up to 240 min of treatment (Fig 4C and 4D).

Bottom Line: The cytotoxic effects of peptides were tested against human erythrocytes, WRL-68 normal liver cell line, and NL-20 normal lung cell line.The results revealed that none of the thirteen peptides have cytotoxic or hemolytic effects at their MIC values.RN7IN6 showed a strong affinity to target proteins; autolysin, pneumolysin, and pneumococcal surface protein A (PspA) based on rigid docking studies.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.

ABSTRACT
Antimicrobial peptides (AMPs) represent promising alternatives to conventional antibiotics in order to defeat multidrug-resistant bacteria such as Streptococcus pneumoniae. In this study, thirteen antimicrobial peptides were designed based on two natural peptides indolicidin and ranalexin. Our results revealed that four hybrid peptides RN7-IN10, RN7-IN9, RN7-IN8, and RN7-IN6 possess potent antibacterial activity against 30 pneumococcal clinical isolates (MIC 7.81-15.62µg/ml). These four hybrid peptides also showed broad spectrum antibacterial activity (7.81µg/ml) against S. aureus, methicillin resistant S. aureus (MRSA), and E. coli. Furthermore, the time killing assay results showed that the hybrid peptides were able to eliminate S. pneumoniae within less than one hour which is faster than the standard drugs erythromycin and ceftriaxone. The cytotoxic effects of peptides were tested against human erythrocytes, WRL-68 normal liver cell line, and NL-20 normal lung cell line. The results revealed that none of the thirteen peptides have cytotoxic or hemolytic effects at their MIC values. The in silico molecular docking study was carried out to investigate the binding properties of peptides with three pneumococcal virulent targets by Autodock Vina. RN7IN6 showed a strong affinity to target proteins; autolysin, pneumolysin, and pneumococcal surface protein A (PspA) based on rigid docking studies. Our results suggest that the hybrid peptides could be suitable candidates for antibacterial drug development.

No MeSH data available.


Related in: MedlinePlus