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3044 Novel Antimicrobial Peptide-Based Blood Safety Strategies for Bacterial Reduction

Monday, December 8, 2008, 5:30 PM-7:30 PM
Hall A (Moscone Center)
Poster Board III-126

Ketha V. K. Mohan, Ph.D.*, Shilpakala Sainath Rao, Ph., D.* and Chintamani D Atreya, Ph.D.*

Division of Hematology, Center for Biologics Evaluation & Research, F.D.A., Bethesda, MD

Bacterial contamination of blood and blood components is a major safety concern in transfusion medicine. In order to facilitate safer transfusion products to the end users, there is a critical need for novel proof-of-concept ideas for pathogen reduction, which are different from the current ones that outweigh the associated toxicity and/or contamination risk. Present study involves use of nine novel synthetic antimicrobial peptides (four originated from thrombin-induced human platelet derived antimicrobial proteins named PP1-PP4 and five having 1-5 repeats of arginine and tryptophan residues, named DP1-DP5. These peptides were tested on plasma samples spiked with 10-fold dilutions of 5 different bacteria (Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, and Bacillus cereus) that are important to the field of transfusion medicine and analyzed whether these spiked plasma samples could be cured of the pathogens. Each spiked sample was incubated with a peptide (PP1-PP4 and DP1-DP5) for 2 hours at 37°C. Following incubation, a fixed volume of the inoculum was plated on nutrient agar plates and incubated overnight at 37°C for colony count. Spiked sample without any peptide was included as control. Results revealed that out of nine peptides tested, while DP3 and DP4 were active against all 5 organisms tested resulting in 50-100 % of inhibition of specific organisms, peptide PP4 was only active against E. coli, P. aeruginosa and Bacillus cereus resulting in a 30-100% reduction in the CFU/ml compared to the controls.

 

Table 1
Organism
Colony count expressed in %
Control
PP1
PP2
PP3
PP4
DP1
DP2
DP3
DP4
DP5
S. aureus
100
90
100
26
100
100
20
10
56
100
E. coli
100
95
100
100
71
100
93
4
18
85
P. aeruginosa
100
100
100
100
0
100
0
0
13
100
K. pneumoniae
100
100
100
100
100
74
3
0
0
25
B. cereus
100
100
100
100
50
100
100
25
77
100

 

Based on these results, it appears that peptides used in this study provide a new antibacterial strategy against a range of bacteria and with further studies and refinement, these peptides could prove useful towards bacterial reduction in blood and blood products.

 

The findings and conclusions in this abstract have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH