8 thoughts on “D68 – Badger

  1. Were there any characteristics besides cationic properties that led you to design the cationic peptide you went with?

    1. Thanks for the great question Jared.

      Yes, previous researchers have identified a number of physiochemical properties that appear to be key in conferring antimicrobial activity to certain peptides. As you mention, a high positive charge stands as the primary characteristic and essentially means that these sequences have a relatively high density of lysine and/or arginine amino acids. These peptides also tend to be amphipathic, having both hydrophobic and hydrophilic regions. When folded into their native conformation, they form one or more alpha helix. All of these characteristics and other physiochemical properties were used to select the chosen peptide.

    1. Good question Josh. It would be interesting to test the peptide against gram-positive bacteria such as species in the Staphylococcus and Clostridium genus’s. Research indicates that some gram-positive bacteria including Salmonella typhimurium possess defense pathways to reduce the extracellular anionic charge in response to cations. These pathways may be less prevalent in gram-positive species meaning that the peptide could be more effective.

    1. Salmonella Typhimurium itself is pathogenic to humans causing Salmonella gastroenteritis or food poisoning. Salmonella Typhi is closely related and much more pathogenic, causing typhoid fever in humans. Salmonella Typhimurium is used for drug discovery because it is less pathogenic in humans and therefore safer to work with, while also causing typhoid fever like symptoms in mice. Consequently, once potential drugs are identified, mouse models infected with Salmonella Typhimurium are invaluable in the next stage of preclinical development.

  2. Can you explain more about the defense pathway in salmonella that may have kept your peptide from being effective?

    1. Excellent question Eva. Although not well understood, defense pathways have been postulated and investigated as bacterial defenses against cationic peptides. First its important to understand that prokaryotes tend to have a higher concentration of anionic phospholipids such as cardiolipin in their membranes and for this reason cationic peptides can selectively disrupt the membranes of bacteria while remaining relatively nontoxic to eukaryotic cells. Cationic peptides interact ionically with these anionic lipids headgroups, sequestering them and thereby disrupting the bulk composition of the membrane or mechanically rupturing the membrane.

      To mitigate against this damage, evidence suggests that some prokaryotic species have enzymes (essentially flipases) that translocate these anionic lipids from the outer membrane thereby reducing the negative charge, leaving fewer sites available for cations to interact. Under these conditions, this type of peptide becomes less effective.

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