Journal article
Improved in vitro evaluation of novel antimicrobials: potential synergy between human plasma and antibacterial peptidomimetics, AMPs and antibiotics against human pathogenic bacteria
Department of Systems Biology, Technical University of Denmark1
Bacterial Ecophysiology and Biotechnology, Department of Systems Biology, Technical University of Denmark2
University of Copenhagen3
University of Southern Denmark4
Department of Micro- and Nanotechnology, Technical University of Denmark5
Center for Electron Nanoscopy, Technical University of Denmark6
Stable peptidomimetics mimicking natural antimicrobial peptides (AMPs) have emerged as a promising class of potential novel antibiotics. In the present study, we aimed at determining whether the antibacterial activity of two α-peptide/β-peptoid peptidomimetics against a range of bacterial pathogens was affected by conditions mimicking in vivo settings.
Their activity was enhanced to an unexpected degree in the presence of human blood plasma for thirteen pathogenic Gram-positive and Gram-negative bacteria. MIC values typically decreased 2- to 16-fold in the presence of a human plasma concentration that alone did not damage the cell membrane. Hence, MIC and MBC data collected in these settings appear to represent a more appropriate basis for in vivo experiments preceding clinical trials.
In fact, concentrations of peptidomimetics and peptide antibiotics (e.g. polymyxin B) required for in vivo treatments might be lower than traditionally deduced from MICs determined in laboratory media. Thus, antibiotics previously considered too toxic could be developed into usable last-resort drugs, due to ensuing lowered risk of side effects.
In contrast, the activity of the compounds was significantly decreased in heat-inactivated plasma. We hypothesize that synergistic interactions with complement proteins and/or clotting factors most likely are involved.
Language: | English |
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Publisher: | Elsevier BV |
Year: | 2016 |
Pages: | 72-82 |
ISSN: | 17697123 and 09232508 |
Types: | Journal article |
DOI: | 10.1016/j.resmic.2015.10.002 |
ORCIDs: | 0000-0002-2822-1927 , Mateiu, Ramona Valentina and Gram, Lone |