Penicillin and Antibiotic Resistance

Penicillin and Antibiotic Resistance


In 1928, Alexander Fleming discovered that a fungus contaminating his petri dishes had released a powerful antibiotic that killed the surrounding bacteria. He named this antibiotic “penicillin”. Nearly two decades later, after years of intense cooperation between scientists, manufacturers, and government agencies, penicillin was made
broadly available. In 1945, using X-ray crystallography, Dorothy
Hodgkin determined the chemical structure of penicillin, a discovery that fueled the
quest to synthesize the drug. In 1952, a form of penicillin suitable for
oral use – called Penicillin V – was developed. And in 1957, penicillin V was produced synthetically
for the first time, laying the foundation for the development and synthesis of new
penicillin antibiotics. Penicillin is effective for treating bacterial
infections because it disrupts an essential process in the bacterial life cycle: the creation of the bacterial cell wall. The cell wall in most bacteria consists of
a lipid bilayer membrane and a mesh-like peptidoglycan layer. Gram-positive bacteria build a thick peptidoglycan sheath around a single membrane, while Gram-negative bacteria typically build a thin layer of peptidoglycan between two membranes. Water constantly enters bacterial cells by
osmosis, building up pressure on the cell membrane. Peptidoglycan allows the cell to resist this
pressure by providing structural support forthe membrane. Penicillin prevents bacteria from building
their peptidoglycan layer, causing the bacteria to burst under pressure. Let’s take a closer look at how penicillin
acts at the molecular level. Peptidoglycan is made up of small building
blocks, each composed of two sugars connected to a short chain of amino acids with a peptide bridge
extending to the side. These sugars are assembled into chains, which
are then crosslinked via the peptide bridges to form a tough peptidoglycan matrix. The enzyme D-alanyl-D-alanine carboxypeptidase/transpeptidase,
also known as Penicillin-Binding Protein, assists with peptidoglycan matrix assembly
by creating the crosslinks between the chains. Penicillin antibiotics block this enzyme by
making a direct bond to a key serine amino acid in its active site. The active portion of penicillin is a beta-lactam ring. It is chemically reactive,
and opens up to form a bond to the active site serine. This inactivates the enzyme and prevents proper
formation of the peptidoglycan matrix. The beta-lactam ring is found in both natural
and synthetic antibiotics that are structurally similar to penicillin. Beta-lactam antibiotics are effective against
many types of bacterial infections, and have helped to save countless human lives. However, bacterial communities are living
things, and like any other living thing, they adapt to survive. To protect themselves from antibiotics, bacteria
developed resistance mechanisms. For example, MRSA, a strain of Staphylococcus
aureus, expresses Penicillin Binding Protein 2a, which has an altered active site that
doesn’t bind beta-lactam antibiotics. Bacteria can also express special Beta-lactamase
enzymes, which bind to beta-lactam antibiotics and break the essential beta-lactam ring,
making the antibiotic ineffective. Medical scientists worked quickly to develop
new drugs to fight resistance. Some of these drugs block beta-lactamase directly,
leaving the antibiotic free to inhibit Penicillin-Binding proteins. Other new beta-lactam drugs are not
recognized or not broken down by some beta-lactamases. Unfortunately, in the face of overuse and
misuse of antibiotics, bacteria continue to develop ways to resist the action of new drugs. Many genes that are crucial in antibiotic
resistance are encoded on small circular pieces of DNA called plasmids. These plasmids can be passed from one population
of bacteria to another, and then from generation to generation. One such particularly dangerous gene is NDM-1. Bacteria possessing this gene can build the
New Delhi metallo-beta-lactamase enzyme. These types of enzymes can break down almost
all known beta-lactam drugs, posing a major global health threat. Today, less than 100 years since Fleming’s
discovery, we are in the middle of an arms race with pathogenic bacteria. Using our growing knowledge of the structural
biology of bacterial enzymes, the medical community is looking for new ways to target
the weak points of bacteria.

20 Replies to “Penicillin and Antibiotic Resistance”

  1. To contribute subtitles to this video in your language, use this link: http://www.youtube.com/timedtext_video?v=m0V6DRJBBGY&ref=share

  2. Sir i understand completely and all world is know about drug Resistant Typhoid in Pakistan XDR typhoid Extremely drug Resistant also meropenim Sir here is my one question many Medicine companies selling there Antibiotics one just 05 rupees than other same are 50 rupees why ….If i am not wronge low power medicine or not completely distroy the Bacteria when the 3rd generation Antibiotics is powerful but patients are not treated…

  3. The second or third line when he said it took almost 20 years for penicillin to be broadly available it's just so sad. I respect that bacteria want to live but I also respect that we need to not let them live inside of us although of course they have to have some part inside of us because otherwise the overdosing of antibiotics will of course cause the immunity and then the morphing and then pretty soon nothing works we know that. So it's almost like we got to kill 'em when we have to and make peace when we can, sort of a Tom Robbins approach.

  4. I hope we can learn to use bacteriophage therapy more. It's targeted to a specific bacterium, and leaves the rest of the microbiome.
    I wonder if then we could cycle antibiotics in and out of use to retain their novelty.
    I wonder if antibiotics affect mitochondria.

  5. Antibiotic Resistance is a made up theory by drug laboratories; so that we doctors use different and more expensive antibiotics —
    I believed on it until I saw and proved that the problem was not the bacteria resisting the drug it was bad quality drug that was not well stored and lost it's effectiveness "that simple" the rest is a made up story like this

  6. Yea keep discouraging antibiotic use. Hope you enjoy dying. That’s what these looney toons want us to go back to. A world without much needed antibiotics. They can’t prove if a person needs antibiotics so they make them wait and if they get sicker they give antibiotics. Sound strategy so long as the person doesn’t end up dying before getting treatment.

  7. Awesome video! Thanks for sharing. I would comment on 3:30 where the wording seems to suggest bacteria didn’t evolve resistance to penicillin but Intelligently developed it.

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