NDLI: In Vitro Activities of Designed Antimicrobial Peptides against Multidrug-Resistant Cystic Fibrosis Pathogens

Content Provider	PubMed Central
Author	Schwab, Ute Gilligan, Peter Jaynes, Jesse Henke, David
Copyright Year	1999
Abstract	The emergence of multidrug-resistant pathogens renders antibiotics ineffective in the treatment of lung infections in patients with cystic fibrosis (CF). Designed antimicrobial peptides (DAPs) are laboratory-synthesized peptide antibiotics that demonstrate a wide spectrum of antibacterial activity. Optimal conditions for susceptibility testing of these peptides have not yet been established. Medium composition is clearly a major factor influencing the results and reproducibilities of susceptibility tests. Using time-kill assays, we tested the effects of different media and buffers on the bactericidal activities of the peptides D2A21 and D4E1 on Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa ATCC 27853. Each peptide at 1 and 5 μM was incubated with bacteria in the different media and buffers. Both peptides were most active in Tris-HCl buffer against S. aureus and P. aeruginosa. Among the more complex media tested, modified RPMI medium was the medium in which the peptides demonstrated the highest activity, while it supported the growth of the bacteria. The broth microdilution technique was used to test the activities of D2A21 and D4E1 in modified RPMI medium against multidrug-resistant pathogens from patients with CF. The MICs of DAPs for methicillin-resistant S. aureus ranged from 0.25 to 4 μg/ml, those for multidrug-resistant P. aeruginosa ranged from 0.125 to 4 μg/ml, those for Stenotrophomonas maltophilia ranged from 0.5 to 32 μg/ml, and those for Burkholderia cepacia ranged from 32 to ≥64 μg/ml. When the activity of peptide D2A21 was compared with that of the tracheal antimicrobial peptide (TAP), D2A21 had greater potency than TAP against P. aeruginosa. In addition, no difference in the MICs of D2A21 was seen when it was tested in nutrient broth supplemented with NaCl at different concentrations. Thus, DAPs are a class of salt-insensitive antibiotics potentially useful in the treatment of CF patients harboring multidrug-resistant P. aeruginosa.
Starting Page	1435
File Format	PDF
ISSN	10986596
e-ISSN	10986596
Journal	Antimicrobial Agents and Chemotherapy
Issue Number	6
Volume Number	43
Language	English
Publisher	American Society for Microbiology
Publisher Date	1999-06-01
Access Restriction	Open
Rights Holder	American Society for Microbiology
Subject Keyword	Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Infectious Diseases Pharmacology Pharmacology (medical)

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