Journal article
Novel antimicrobial peptides that inhibit gram positive bacterial exotoxin synthesis
PloS one, Vol.9(4), pp.e95661-e95661
2014
DOI: 10.1371/journal.pone.0095661
PMCID: PMC3991719
PMID: 24748386
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.
Details
- Title: Subtitle
- Novel antimicrobial peptides that inhibit gram positive bacterial exotoxin synthesis
- Creators
- Joseph A Merriman - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of AmericaKimberly A Nemeth - The Procter & Gamble Company, Cincinnati, Ohio, United States of AmericaPatrick M Schlievert - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, United States of America
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.9(4), pp.e95661-e95661
- DOI
- 10.1371/journal.pone.0095661
- PMID
- 24748386
- PMCID
- PMC3991719
- NLM abbreviation
- PLoS One
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Publisher
- United States
- Grant note
- R01 AI074283 / NIAID NIH HHS U54 AI57153 / NIAID NIH HHS
- Language
- English
- Date published
- 2014
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984001206102771
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