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Novel antimicrobial peptides that inhibit gram positive bacterial exotoxin synthesis.
- Source :
-
PloS one [PLoS One] 2014 Apr 18; Vol. 9 (4), pp. e95661. Date of Electronic Publication: 2014 Apr 18 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- Gram-positive bacteria, such as Staphylococcus aureus, cause serious human illnesses through combinations of surface virulence factors and secretion of exotoxins. Our prior studies using the protein synthesis inhibitor clindamycin and signal transduction inhibitors glycerol monolaurate and α-globin and β-globin chains of hemoglobin indicate that their abilities to inhibit exotoxin production by S. aureus are separable from abilities to inhibit growth of the organism. Additionally, our previous studies suggest that inhibition of exotoxin production, in absence of ability to kill S. aureus and normal flora lactobacilli, will prevent colonization by pathogenic S. aureus, while not interfering with lactobacilli colonization. These disparate activities may be important in development of novel anti-infective agents that do not alter normal flora. We initiated studies to explore the exotoxin-synthesis-inhibition activity of hemoglobin peptides further to develop potential agents to prevent S. aureus infections. We tested synthesized α-globin chain peptides, synthetic variants of α-globin chain peptides, and two human defensins for ability to inhibit exotoxin production without significantly inhibiting S. aureus growth. All of these peptides were weakly or not inhibitory to bacterial growth. However, the peptides were inhibitory to exotoxin production with increasing activity dependent on increasing numbers of positively-charged amino acids. Additionally, the peptides could be immobilized on agarose beads or have amino acid sequences scrambled and still retain exotoxin-synthesis-inhibition. The peptides are not toxic to human vaginal epithelial cells and do not inhibit growth of normal flora L. crispatus. These peptides may interfere with plasma membrane signal transduction in S. aureus due to their positive charges.
- Subjects :
- Amino Acids chemistry
Anti-Bacterial Agents metabolism
Anti-Bacterial Agents pharmacology
Anti-Infective Agents chemistry
Anti-Infective Agents metabolism
Bacterial Toxins biosynthesis
Enterotoxins biosynthesis
Epithelial Cells metabolism
Epithelial Cells microbiology
Female
Gram-Positive Bacteria isolation & purification
Humans
Interleukin-8 biosynthesis
Peptides chemistry
Peptides metabolism
Staphylococcus aureus drug effects
Staphylococcus aureus isolation & purification
Staphylococcus aureus metabolism
Superantigens biosynthesis
alpha-Defensins pharmacology
alpha-Globins chemistry
Anti-Infective Agents pharmacology
Exotoxins biosynthesis
Gram-Positive Bacteria drug effects
Gram-Positive Bacteria metabolism
Peptides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24748386
- Full Text :
- https://doi.org/10.1371/journal.pone.0095661