The Dangers of Antibiotic Resistance Part One

By: Jennifer Brush O’Shaughnessy

WhySci is an ongoing feature providing education of scientific topics in the news. The first installation will run in three parts.

WhySci: The Dangers of Antibiotic Resistance: Reduce Antibiotic Resistance by Identifying Genome of Pathogen

Part One-Scientific Details

  • Bacteria and Antibiotic Mechanism

Part Two-Current news event

  • Antibiotic Resistance

Part Three-Thought provoking solutions

  • DNA Identification of Bacteria and Treatment

 

Imagine a world where you could die of a paper cut. This was every day prior to the 20th Century and could very well be our new norm if antibiotic resistance is not addressed more vigorously.

What are antibiotics? Antibiotics are compounds produced by bacteria or fungi that are harmful to other microbial species. Drugs commonly referred to as antibiotics are made from that mechanism and prescribed to combat bacterial infection. These drugs don’t eliminate viral, fungal or other microbial infections because they target a specific mechanism in bacterial growth.

Why do bacteria become resistant to antibiotics? This will be covered more in Part Two of the series but resistance of bacteria to these drugs has been an ongoing challenge, however it is becoming more newsworthy because some bacteria have become resistant to all of the possible antibiotic drugs currently available. General bacterial resistance happens more rapidly with increased exposure to the antibiotics that are attempting to destroy it.

How was penicillin discovered? Alexander Fleming discovered the anti-bacterial properties of penicillin, the first commercialized antibiotic drug, in 1928; however, the drug wasn’t produced and used on a patient until 1942. He “discovered” penicillin on a typical day in the lab where he grew many types of bacteria on agar plates and struggled with the consistent issue of different molds contaminating the agar plates made to culture bacteria he was studying. On one plate he noticed something unusual and unique-the mold growing on that plate of Staphylococcus aureus had killed the bacteria around it. Depicting the typical scientist about to form a hypothesis, it was said that he observed, “That’s funny.” It seemed that the mold was producing a chemical (antibiotic) that was toxic to the bacteria. It took a few more years to figure out how to extract this toxin and produce enough mold to create enough “mold juice” (antibiotic) to test on mice and eventually humans. Scaling up the antibiotic to be produced on a mass level took cooperation of many scientists and corporations. By the end of World War II, penicillin was being used to treat wounded in battle as well as civilians.

Why don’t antibiotics work on other types of infections? Different antibiotics have different mechanisms of action, but penicillin is the first antibiotic discovered and put into medical use so I will use that as my example. To simplify, bacteria are classified as having cells lacking a true nucleus or procaryotic, whereas cells in the human body are eucaryotic, or containing a true nucleus. This is important to understand if you have a drug with a mechanism of action targeted on the specifics of a procaryotic organism, because it shouldn’t damage eucaryotic cells. Bacteria also have a cell wall structure that differs from eucaryotic cells. Using Staphylococcus aureus as an example (also the bacteria being referred to when there is a “staph” infection), it needs to build a “wall” around a cell to keep the dangers out and the healthy nutrients in. It is kind of like in medieval days when they built walled cities like one of my personal favorites, San Gimignano, in Tuscany, Italy. The people could go about their daily business within the city walls without worrying about being attacked by invaders. Like most of nature if you look closely enough, a cell wall in S. aureus has a peptidoglycan that is a thin sheet comprised of a repeating pattern of sugar derivatives and amino acids bound together by peptide cross-links.

The peptidoglycan is another feature that is only present in procaryotes. This difference allows penicillin to kill bacteria while not killing you. When bacteria divide, this cell wall needs to be split open to get to all the important replication bits, and it is re-built from the fractured pieces of the wall of two new cells. In the case of S. aureus, the last step of building a complete cell wall is to form the peptide cross-links between adjacent glycan chains. The reason I bore you with all of the scientific terminology is that this unusual type of bond formation called transpeptidation is what penicillin inhibits. This leads to a breach in the strength of the wall and the ultimate lysis and death of the cell. The invaders have breached the wall and the town is certainly in for some pillaging and destruction. So, after we know the mechanism of action, we can answer two important questions of distinction.

Why don’t antibiotics work on other forms of infection such as the viral flu? Viruses don’t have cell walls; they have a protein coat. They don’t build the same patterned peptidoglycan or use transpeptidation. Therefore, antibiotics such as penicillin are rendered useless against them. As for the other pathogens that I mentioned, fungal cell walls are closer to plant cell walls and are not joined by transpeptidation so penicillin is ineffective in eliminating those infections. Microbial is a used as a catch phrase for all of the tiny (single cell or cell clusters) pathogens that can cause disease (viruses and bacteria included) such as mycobacterium, protozoa, etc. Protozoa, which cause malaria, lack cell walls so penicillin won’t work to inhibit infections caused by those. Mycobacteria, the cause of Tuberculosis (TB), also lack a typical bacterial cell wall so are resistant to penicillin.

Why does it take a bit of time before you start feeling better when taking antibiotics? If you are on an antibiotic that is effective against your bacterial infection (has not become resistant, which I will cover in Part Two), it takes a bit of time to take effect because in the case of penicillin, it only works on those cells dividing and making new cell walls. There are already a whole bunch of cells with complete cell walls that were making you feel bad enough to go to the doctor in the first place. Antibiotics are like a helping partner to your immune system. Your immune system still has the responsibility to get rid of those foreign bacterial invaders, but the antibiotic helps it not get outnumbered. The antibiotic takes care of all of the dividing and growing bacteria while your immune system can focus on getting rid of the ones already there. So, there is a bit of a time delay before you are feeling better. This is one reason infection is so dangerous to immunocompromised people-their immune system is still overloaded by the bacteria already there.

Now that we have the basics of the antibiotic effects of penicillin on bacteria, join me for Part Two to understand why resistance to these drugs has become so dangerous for us.

Glossary of terms (in alphabetical order):

Amino Acid is a building block of a protein. It contains a carboxylic acid group (-COOH) and an amino group (-NH2). 20 amino acids are available in nature to combine to make various proteins.

Antibiotics are compounds produced by bacteria or fungi that are harmful to other microbial species. The term may be used for those chemicals naturally produced by the microbe or a drug produced based on the properties of the natural chemical.

Eucaryotic (also spelled Eukaryotic) refers to a cell or organism having a true nucleus.

Glycan is a synonym of polysaccharide (linked monosaccharides, or sugars).

Immunocompromised describes the lack of an adequate immune response, often due to a pre-existing disease or condition that renders the immune system ineffective.

Lysis is the rupture of a cell, resulting in the loss of cell contents.

Mycrobial is a term to describe a cell or cell clusters that are generally able to carry out life processes of growth, energy generation and reproduction independently of other cells, thus distinct from cells of animals and plants.

Nucleus is a membrane-enclosed structure containing the genetic material (DNA) of a cell.

Penicillin is the first commercially created antibiotic used to treat human infection by bacteria.

Peptide is another name for protein but generally refers to a linear nature.

Peptidoglycan is the rigid layer of bacterial cell walls, a thin cheet composed of N-acetylglucosamine, N-acetylmuramic acid and a few amino acids.

Procaryotic (also spelled Prokaryotic) refers to a cell or organism lacking a true nucleus, usually having its DNA in a single molecule.

Transpeptidation is the formation of peptide bonds between the short peptides present in the cell wall polymer, peptidoglycan.

 

References:

Jones and Bartlett Bioscience, Cells; www.bioscience.jbpub.com/MBIO41314.aspx; Donachie, W.D. and Begg, K.G., 2005-02-15, accessed 2016-10-12.
Biology of Microoganisms; Brock, Thomas D. and Madigan, Michael T., Prentice-Hall, Inc. (Simon & Schuster), New Jersey, 1988.
Good Germs, Bad Germs: Health and Survival in a Bacterial World; Sachs, Jessica Snyder, Hill and Wang, New York, 2007.
American Chemical Society, Historic Chemical Landmarks, Discovery and Development; www.acs.org/content/acs/en/education/whatischemistry/landmarks/flemingpenicillin.html; 1999-11-19, accessed 2016-10-12.

 

Jen Brush pixBy Jennifer Brush O’Shaughnessy
Biography:
Jennifer is a former scientist of molecular biology, current scientist of “young male development;” studying her two teenage boys in their natural habitat. She married the boy in the apartment next door sixteen years ago, and is now living with her family and dog in California. She is a former member of The Writing Mamas Salon and is working on writing a book based on discoveries made from genealogical research of her father’s family’s lives over the past 400 years.  www.linkedin.com/in/jenniferbrushoshaughnessy

 

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