This was the 6th day of my week at UT. Trying to explore different paths for the less-structured individual. Science like language does have a lot of rules, but also has some interesting diversity and exception. It tends to minimize the inward search for diversity and exception, though, directing it outwards instead.
With my medical visit the day before, I decided to attend a talk on peptides and biofilms to see if more basic science would offer insight into strategies to improve wound healing. This was with an eye toward being a self-healer, or medicine woman. I know that I am not good enough to do this without the help of others, but I develop insight pretty quickly. Although it sounds selfish, the restraint here comes from a lack of confidence that I would really understand someone else’s problems well enough. To go through a medical education successfully, one has to learn to worship “health”, treating the healthy body with great reverence. A person with illness struggles with the language of medicine. Although I will never be formally medically educated, if someone wanted my help, I would obviously do my very best to heal and not hurt them.
So part of the talk centered around anaerobes – the kind that cause acne, which isn’t that scary. The biofilm part of the talk though evolved to study the gram-negative aerobe pseudomonas aeruginosa, which is the organism that is involved in swimmer’s ear, and also many skin infections. Diabetics get these infections because the bacteria thrive on sugar, but they also resist many antibiotics. I once had a pretty bad ear infection for a while, and then ended up growing it out on a plate, and seeing the slight green color that these pseudomonas colonies have. With this info, I was able to get an antibiotic that worked to heal it after many months. What I would later discover, during a period when other antibiotics were being used on other infections and I developed an ear infection because pseudomonas was the only thing left that could grow, was that these bacteria don’t grow at low pH. So, simply putting a vinegar-hydrogen peroxide solution in my ear provided a lot of relief without antibiotic. The speaker showed some movies of bacteria walking, and some studies to suggest that a snail slime-like trail of the secreted exopolysaccharide molecule PSL acts like a glue to make the bacteria form a film that is highly resistant to antibiotic. Inhibiting the PSL pathway might disrupt the biofilm. I wondered if pH somehow also acts along this pathway. The first step would be to know if pH has an influence on the biofilm formation. A little on-line literature search later would indicate that pH does seem to influence biofilm growth on another gram-negative organism Burkholderia pseudomallei, but probably through a quorum sensing pathway [octanoyl-homoserine lactone (C8-HSL)]. The paper showed large differences in some media, but pretty consistent trends in that: 1) lower temperature promoted biofilm formation, 2) maintaining neutral pH promoted biofilm formation, and 3) higher levels of glucose promote biofilm formation. The temperature effect seems somewhat sensitive to large vs. small colony phenotypes within the distribution of tested genetic variants.
Another part of the same talk dealt with AMPs (antimicrobial peptides) and how they differentially interact with bacterial and eukaryotic lipid membranes to allow molecules like protons, or nucleic acids or antibiotics to penetrate the membrane or not. I thought these amphiphilic peptides were pretty interesting. There were a few different models for how they interact with membranes (see Schmidt and Wong, 2013), the positively charged arginines and lysines possibly lining up against the negatively charged headgroups of the lipids or nucleic acid double helices in a 3 amino acid pattern suggestive of a helix. I wondered whether the arginines and lysines are directed inward into a pore like conformer as the helix translocates the membrane, the hydrophilic part allowing water molecules and protons to penetrate the membrane through the pore. I later dismissed the idea because hydronium ions are positively charged and the lysines and arginines would be as well, so there would be electrostatic repulsion. It turns out though, that there do seem to be cases where this happens with cations, and the way it happens is that the helix stability provides enough structural integrity to move the whole positively charged amino acid sequence as a unit to allow cations to rush in where the positively charged amino acids had been formerly. This might allow a proton differential to form across the membrane generating an inhibitory pH effect on the bacteria that might inhibit biofilms or work along some other nonbiofilm-related pathway.
I think it more likely that these kinds of channeling mechanisms would operate better in the context of the peptides being anchored to a larger protein, where like a robotic arm that swings out from a hinge, it would have an anchor. The unanchored peptide would need something to pull the helix across on the other side, and the exposed part would probably be too small to make it specific enough. A 2 amino acid group that sticks out across a membrane might correspond to almost anything, and one would be nonselectively pulling all sorts of things through the membrane, unless there were other mechanisms at work.
Stepping back a little from all this for a bigger view, I think that most bacteria have a function both in nature and in our bodies. When their equilibrium is disrupted and they become pathological to an individual (causing pain and damage), one probably has to think pretty carefully about how to restore balance. It helps to understand. Some people need antibiotics more than others do. Diabetics with open wounds fall into that category, but antibiotic use still probably needs a thoughtful case-by-case approach. Like anarchism, the scale of influence of the bacterium has to correspond to its size for it to peacefully survive and not be pathological in the context of a larger organism. So biofilm regulators vs. drones may be a better strategy.
Toward the end of the day, I had the pleasure of attending a talk by an Egyptian-American news reporter who got into the news field by freelancing. He discussed his point of view on the various Arab springs, and the crisis in the Ukraine, and how language influences our perception. We struggled a little to talk about the language of the various revolts. In Egypt, was it a coup or a revolution, or a couvolution? Did it matter whether military service was obligatory or not in Egypt, forcing guns and defensive/offensive training on all male Egyptian citizens pretty equally? Did this make the military representative? How does legitimacy relate to representation? In Eastern Ukraine, were the armed occupiers of the government buildings separatists, or simply squatters with an adjustment disorder to the new regime? With the recent seizing of the media broadcasting stations in Eastern Ukraine to broadcast Russian news, I’m starting to see that the choice of a voice in the politics of dissent has consequence. If the “separatists” feel like they have to use a Russian voice to have the environment that they want, it is a venn diagram association that is larger than who they really are, which are presumably Ukranian-Russian individuals who are organizing in an armed and forceful way in opposition to the change in Ukrainian government, using the momentum of events in Crimea. Their sphere of influence cannot be Russia, or indeed the entire world.
This was again a day where several hats were switched and sometimes stitched together: a medical hat, a scientist hat, an international studies hat, a writing hat.