All posts by keshav01pd2014

A Silver Bullet?

When my sister went to get her ears pierced over the summer, my mother recounted how, instead of using devices like the sterilized piercing guns used today, Indian people used to use thin wires of silver to pierce their ears because of its supposed antimicrobial properties. This intrigued me. Of course I had heard of molecules like penicillin that could kill off bacteria, but never before had I considered that a single, naturally occurring element would be able to accomplish the same. How does this seemingly benign molecule cause so much damage?

The transition metal itself is biologically inert; the real structural damage stems from its Ag+ ion. This is released when Ag comes into contact with moisture (Kenyon University & Garduque), and does its work inside the microbe itself. I stopped as soon as I read that last part. Something didn’t seem right. I had learned from my AP Biology class that the majority of cell membranes are hydrophobic. They consist mainly of a phospholipid bilayer with the polar hydrophilic heads facing outwards into the environment and inwards towards the cell’s cytoplasm, and the long, non-polar hydrophobic tails made of hydrocarbons chains in-between. These tails don’t like to let polar atoms and molecules in and out by themselves, and I thought it highly unlikely that microbes would have special protein channels built to let in damaging substances. So how did these Ag+ molecules get in in the first place?

figure_04_14_labeled

Figure 1: The Phospholipid Bilayer

(Midlands Technical College, n.d.)

A while of digging later, I had no definitive answer. Some research hypothesized that the ions got through via protein channels made for other ions (Kenyon University & Garduque), but since there wasn’t any conclusive evidence I still remained somewhat skeptical. I continued to research the effects of the Ag+ ions, tough, and the evidence I found in favor of its microbial properties was strong enough for me to overlook this tiny blip.

What I found was that Ag+ works in three major ways: by reacting with the disulfide (R-S-S-R) and sulfhydryl (R-S-H) groups of microbial protein structures, by interacting with the microbial DNA, and by damaging the membrane structures of the cells. In the first method, the interactions of the ion change the quaternary (outer) structure of some of the microbes key proteins and enzyme, leaving it unable to function properly. The ion reacts to form, “a stable S-Ag” bond with the sulfhydryl-containing compounds, which are involved in, “trans-membrane energy generation and ion transport,” located in the microbial cell membrane, and are also believed to, “take part in catalytic oxidation reactions that result in the formation of disulfide bonds,” which are key components of a protein’s outer structure. The latter doesn’t involve Ag+ acting as reactant, but rather as a catalyst between existing the oxygen and hydrogen portions of the sulfhydryl groups. This reaction also ends up releasing H2O as a product (Jung, Koo, Kim, Shin, Kim & Park)

500px-Quaternary_structure

Figure 2:“Structure of the protein 1EFN, with focus on the quaternary structure.”

(Wikipedia, 2012)

Next, while it is clear that the Ag+ ions do have effects on microbial DNA, it is unclear exactly how it interacts with the DNA. Some scientists suggest that, “…they interact preferentially with bases in the DNA (Jung, Koo, Kim, Shin, Kim & Park),” while others think that the ions’ various other reactions in the cell, “…lead to an increased production of reactive oxygen species,” that in turn damages the microbe’s DNA, eventually leading to its death (Morones-Ramirez, Winkler, Spina & Collins, 2013). Finally, the microbe’s increased cell membrane permeability, which is also said to occur as a byproduct of these reactions and subsequent metabolic disruption and homeostatic iron levels, which, “…[restores] antibiotic susceptibility to a resistant bacterial strain (Morones-Ramirez, Winkler, Spina & Collins, 2013).”It is important to note, however, that this does not reverse the bacterial resistance, only temporarily weakens it.

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Figure 3: “Figure 3. Treatment of cells with Ag+ results in DNA condensation, cell wall damage, and silver granule formation. (A) E. coli and (B) S. aureus cells with and without Ag+ treatment were observed with transmission electron microscopy (Feng et al., 2000).”

(Kenyon University, n.d.)

As much as it would be great to regard the Ag+ ion as an end to all our troubles, it’s not without its side effects. Some people are allergic to silver (Elsner & Hipler, 2006), and those that aren’t are in danger of having the element accumulate in their bodies (Fung & Bowen, 1996). Long-term intake can lead to increased levels of skin silver and/or silver sulfide particle levels. Sunlight causes these particles to darken, leading to a skin discoloration known as argyria (Elsner & Hipler, 2006). Furthermore, silver is no different from traditional antibiotics in that it is simply ‘another chemical’ in action. As such, it is plausible that overuse of it may eventually lead to increased silver resistance in bacteria, and then we would simply end up in the same place we are now with the antibiotic resistance problem; at best we’ll just delay our troubles. Still, since there’s little doubt in the actual antimicrobial properties of silver, all of this doesn’t completely take it off the table. If it were possible to distribute the dosages in a way to avoid some of the adverse side effects, we could take advantage of the aforementioned delay. Time is arguably the most valuable resource for humans, and with all of the major medical advances taking place in the modern age, that extra time might be just what we need to come up with a true solution.

Works Cited

Elsner, P., & Hipler, U. -. (2006). Silver in health care: Antimicrobial effects and

safety in use. Biofunctional Textiles and the Skin, 33, 17-34. doi: 10.1159/000093928

Retrieved from

http://www.karger.com/Article/Abstract/93928

Fung, M. C., & Bowen, D. L. (1996). Silver products for medical indications: Risk-

benefit assessment. Clinical Toxicology, 34(1), 119-126. doi: 10.3109/15563659609020246

Retrieved from

http://informahealthcare.com/doi/abs/10.3109/15563659609020246

Jung, W., Koo, H., Kim, K., Shin, S., Kim, S., & Park, Y.

(2008). Antibacterial Activity and Mechanism of Action of the Silver Ion in Staphylococcus aureus and Escherichia coli. Applied Environmental Microbiology, 74(7), 2171-2178 doi:10.11.28/AEM.02001-07.

Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2292600/

Kenyon University. , & Garduque, G. (n.d.). Silver as an antimicrobial agent.

Retrieved from http://microbewiki.kenyon.edu/index.php/Silver_as_an_Antimicrobial_Agent

Midlands Technical College. (Producer). The Phospholipid

Bilayer [Web Graphic]. Retrieved from http://classes.midlandstech.edu/carterp/courses/bio225/chap04/lecture5.htm

Morones-Ramirez, J. R., Winkler, J. A., Spina, C. S., & Collins,

J. J. (2013). Silver enhances antibiotic activity against gram-negative bacteria. Science Translational Medicine, 5(190), 198ra81. doi: 10.1126/scitranslmed.3006276

Retrieved from:

http://stm.sciencemag.org/content/5/190/190ra81

Wikipedia. (Producer). (2012, August 27). Protein structure with focus on the

quaternary structure [Web Graphic]. Retrieved from http://en.wikipedia.org/wiki/File:Quaternary_structure.png

H2O: Simple Molecule, Complex Impact

The first thing I noted when I heard that NASA had landed another rover on Mars was that they were looking for evidence of water. Where there is water, they said, there is potential for life. Water is a substance so common to us humans today that we seldom stop and think about its sheer importance in our lives. It’s so important, in fact, that scientists are going out of their way to find it in other places in the universe; what appears to be abundant here seems to be relatively scarce out there. While it’s common knowledge that our bodies need water to function properly, we use this tiny molecule for much more than just health sustenance. Heating, fire extinction, agriculture, and industrial use are just a few of its many applications (MyHydros, n.d.). In this post, I will focus on the lattermost one because of its very high relevance to both the modern age and to myself, living in a modernized city like Shanghai.

In days gone by, humans generally settled near convenient sources of water (Richards, n.d.). Most of the great ancient civilizations depended on a particular source of water. For example, the Egyptian empire expanded from the Nile River banks, and the majority of the Chinese empire expanded from the Huang He (Yellow River) and Yangtze River basins (Richards, n.d.) Water also facilitated relatively rapid transportation during the era of exploration (15th century) until around the mid 19th century. Any nation(s) that controlled the waters had great power and influence over the rest of the word. (Richards, n.d.) The same appears to be true today.  Modern industrial factories are huge consumers of water, accounting for “…around 88% of water consumption worldwide,” (MyHydros, n.d.), and, in a modernized city like Shanghai, it can seem like one of these behemoths is always just around the corner.

Before getting into the various ways they apply water, however, it is important to have a general understanding of what water is. Most water is made up of tiny molecules composed of two hydrogen atoms and one oxygen atom, and is represented with the molecular formula H2O (Granger, n.d.).  Water is formed when two hydrogen atoms each join to the same oxygen atom with strong, single covalent bonds (i.e. the oxygen and hydrogen atoms are “sharing” electrons). (Granger, n.d.) The shape of this molecule is bent (with a 104.5˚ bond angle) because of the repulsion two lone pairs (i.e. non-bonding pairs) of electrons and the two bonding pairs of electrons (negative charges repel each other) . This bent shape is what gives water some of its unique properties, such as its high heat capacity (Granger, n.d.).

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The Specific Heat Capacities of Different Substances Compared to that of Water

More specifically, water molecules have this high heat capacity due to a property known as hydrogen bonding (Granger, n.d.). Since the element oxygen is more electronegative than the element hydrogen (i.e. it has a greater affinity for electrons than hydrogen), it “hogs” the bonding electrons slightly, giving it a slight negative charge and the hydrogen atoms a slight positive charge (Granger, n.d.). These slightly positive hydrogen atoms are then attracted to the slightly negative oxygen atoms on other water molecules by a relatively strong intermolecular force known as a hydrogen bond. The hydrogen bond is one of the hardest intermolecular bonds to break (i.e. requires the most energy), which is why water can absorb so much heat before evaporating into steam (Granger, n.d.).

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A Diagram Depicting how Hydrogen Bonding Works in Water

Three major water-using companies that rely on these properties include thermoelectric power companies, petroleum refinement companies, and, of course, manufacturing companies (MyHydros, n.d.). Thermoelectric power companies take advantage of water’s gaseous state. They use steam to power the generators to create the electricity that they send out to customers. It is estimated that they use an average of 201,000 million gallons of water a day (MyHydros, n.d.). Other power plants, such as solar and nuclear power plants, also need to use large amounts of water for, “manufacturing, maintenance, and cooling.“ (MyHydros, n.d.) The petroleum industry also takes advantage of superheated steam when refining oil (Freudenrich, n.d.), using over one billion gallons a day. Finally, manufacturing industries rely on water’s high heat capacity. (MyHydros, n.d.) Typically, manufacturing processes generate, “large amounts of heat” (MyHydros, n.d.) due to friction and chemical reactions. When this happens, about 18.2 million gallons of water a day is used to cool down the heated machinery and equipment, presumably to prevent them from ‘burning out.’ These industries use so much water overall that it is said that, “every manufactured product at some point requires water.” (MyHydros, n.d.)

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Example of Industrial Water Usage (Steam is Being Released from the Chimneys)

Water is ubiquitous, so we take it for granted. From our earliest history all the way through to the modern era, water has been the molecular key that allowed us to open the doors of progress, and will continue to be so in the future. In fact, as this is being written, NASA’s Curiosity Rover is sitting over what is possibly a jackpot of evidence that Mars was, in fact, much more aqueous than it appears to be today. This discovery opens up a Pandora’s box of possibilities. Is there actually life on other planets? Could we possibly live on Mars sometime in the future? What else could this discovery lead us too? All of these questions and more have been speculated for many years, and now, thanks to water, it looks like we’re about to find out.

Bibliography:

Freudenrich, C. (n.d.). How Oil Refining Works. Retrieved from http://science.howstuffworks.com/environmental/energy/oil-refining2.htm

Granger, J. (n.d.). The Chemistry of Water: Properties. Retrieved from http://witcombe.sbc.edu/water/chemistryproperties.html

Granger, J. (n.d.). The Chemistry of Water: Structure. Retrieved from http://witcombe.sbc.edu/water/chemistrystructure.html

Kremer, K. (2013, January 19th). ‘Jackpot’: Evidence of Water on Mars found by NASA rover Curiosity. Alaska Dispatch. Retrieved from http://www.alaskadispatch.com/article/jackpot-evidence-water-mars-found-nasa-rover-curiosity

n.p. (n.d.). Industrial Water Usage. Retrieved from http://myhydros.org/more-about-water/industrial-water-usage/

Richards, M. (n.d.). Water in History. Retrieved from http://witcombe.sbc.edu/water/history.html