Inhibition of bacterial biofilm formation and swarming motility by a small synthetic cationic peptide
Cesar de la Fuente-Nunez,Victoria Korolik,Manjeet Bains,Uyen Nguyen,Elena B. M. Breidenstein,Shawn R. Horsman,Shawn Lewenza,Lori L. Burrows,Robert E. W. Hancock +8 more
TLDR
Peptide 1037 shows promise as a potential therapeutic agent against chronic, recurrent biofilm infections caused by a variety of bacteria.Abstract:
Biofilms cause up to 80% of infections and are difficult to treat due to their substantial multidrug resistance compared to their planktonic counterparts. Based on the observation that human peptide LL-37 is able to block biofilm formation at concentrations below its MIC, we screened for small peptides with antibiofilm activity and identified novel synthetic cationic peptide 1037 of only 9 amino acids in length. Peptide 1037 had very weak antimicrobial activity, but at 1/30th the MIC the peptide was able to effectively prevent biofilm formation (>50% reduction in cell biomass) by the Gram-negative pathogens Pseudomonas aeruginosa and Burkholderia cenocepacia and Gram-positive Listeria monocytogenes. Using a flow cell system and a widefield fluorescence microscope, 1037 was shown to significantly reduce biofilm formation and lead to cell death in biofilms. Microarray and follow-up studies showed that, in P. aeruginosa, 1037 directly inhibited biofilms by reducing swimming and swarming motilities, stimulating twitching motility, and suppressing the expression of a variety of genes involved in biofilm formation (e.g., PA2204). Comparison of microarray data from cells treated with peptides LL-37 and 1037 enabled the identification of 11 common P. aeruginosa genes that have a role in biofilm formation and are proposed to represent functional targets of these peptides. Peptide 1037 shows promise as a potential therapeutic agent against chronic, recurrent biofilm infections caused by a variety of bacteria.read more
Citations
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Strategies for combating bacterial biofilms: A focus on anti-biofilm agents and their mechanisms of action
TL;DR: The molecules considered here might be used to treat biofilm-associated infections after significant structural modifications, thereby investigating its effective delivery in the host and minimum effective concentration must be capable of eradicating biofilm infections with maximum potency without posing any adverse side effects on the host.
Journal ArticleDOI
Bacterial biofilm development as a multicellular adaptation: antibiotic resistance and new therapeutic strategies.
TL;DR: Novel strategies that specifically target the biofilm mode of growth have been recently described, thus providing the basis for future anti-biofilm therapy.
Journal ArticleDOI
The value of antimicrobial peptides in the age of resistance
Maria Magana,Muthuirulan Pushpanathan,Ana L. Santos,Leon G. Leanse,Michael Fernandez,Anastasios Ioannidis,Marc A. Giulianotti,Yiorgos Apidianakis,Steven B. Bradfute,Andrew L. Ferguson,Artem Cherkasov,Mohamed N. Seleem,Clemencia Pinilla,Cesar de la Fuente-Nunez,Themis Lazaridis,Themis Lazaridis,Tianhong Dai,Richard A. Houghten,Robert E. W. Hancock,George P. Tegos +19 more
TL;DR: The benefits, challenges, and opportunities of using antimicrobial peptides against multidrug-resistant pathogens are identified, advances in the deployment of novel promising antimacterial peptides are highlighted, and the needs and priorities in designing focused development strategies taking into account the most advanced tools available are underlined.
Journal ArticleDOI
Broad-Spectrum Anti-biofilm Peptide That Targets a Cellular Stress Response
Cesar de la Fuente-Nunez,Fany Reffuveille,Evan F. Haney,Suzana K. Straus,Robert E. W. Hancock +4 more
TL;DR: NMR and chromatography studies showed that the peptide acted on cells to cause degradation of (p)ppGpp within 30 minutes, and in vitro directly interacted with ppGpp, suggesting a new approach against biofilm-related drug resistance.
Journal ArticleDOI
Growth Rates Made Easy
TL;DR: The program GrowthRates is introduced that uses plate reader output files to automatically determine the exponential portion of the curve and to automatically calculate the growth rate, the maximum culture density, and the duration of the growth lag phase.
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