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Overview – Bacterial Protein Synthesis Inhibitors (Antibiotics)

by Pravin Shukle, MD
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    00:00 Let's move on to another category of antibacterial agents, the Bacterial Protein Synthesis Inhibitors.

    00:08 So the bacterial protein synthesis inhibitors are narrow spectrum agents.

    00:15 They act either on the 50 S subunit such as linezolid or streptogramins or lincosamines.

    00:22 Or the broad spectrum agents that are like the macrolides.

    00:26 and chloramphenicol.

    00:28 Other broad spectrum agents that act on the 30 S subunit include the tetracyclines, the aminoglycosides.

    00:36 Now let's just quickly do some definitions.

    00:40 Because we need to do this before we go on.

    00:42 There's something called as post-antibiotic effect.

    00:45 So this is an anti-ineffective effect that lasts after the elimination of the antibiotic from the body.

    00:50 That's often because we have some kind of, I wouldn't say permanent but long lasting effect in this case on the 50 or 30 S subunits.

    00:59 Bactericidal means that it kills bacteria.

    01:03 Bacteriostatic means that it just stops the bacteria from replicating but doesn't kill them.

    01:09 So the bacteria are still alive but the numbers aren't increasing.

    01:13 So the other immune mediated, killing of the bacteria can occur unimpeded.

    01:19 The 70 S ribosomal mRNA subunit is composed of a 50 S and a 30 S.

    01:28 Okay, I know 50 plus 30 is 80.

    01:32 And how come 50 plus 30 equal 70.

    01:34 Don't worry about it, the point is that the 50 S and the 30 S make up 70 S unit.

    01:40 Time dependent agents.

    01:43 So these are drugs that have increased killing activity with time.

    01:48 This is different from the concentration dependent killing where the drugs have increased killing activity with concentration.

    01:55 So there you have some basic definitions and we're going to be using them as we go forward in this lecture.

    02:03 Let's go on to the 70 S ribosomal unit.

    02:10 The 70 S ribosomal unit is made up of 50 S and the 30 S units.

    02:15 Now, this is a hamburger.

    02:17 Think of it is as a hamburger bun.

    02:19 So 50 S is top of the bun and the 30 S is the bottom of the bun.

    02:22 So the 30 S is smaller and flatter.

    02:24 The 50 S is bigger and puffier.

    02:26 Now how this works is that you have this charged transfer tRNA on the end there.

    02:33 Bringing in the 7th amino acid.

    02:36 You can see the 7 in there, that's the amino acid.

    02:38 So the charged transferRNA and sits on top of the mRNA, or messengerRNA.

    02:44 And the messengerRNA is the base that determines what the coding is going to be for the protein.

    02:51 Let's pretend for a moment that this particular protein is, or I don't know a protein involved in metabolism.

    02:57 There's a specific code that's coded by mRNA.

    03:00 And it tells the transferRNA which amino acids to bring in.

    03:05 As it goes through the hamburger, it's as if you had a slice of cheese through the hamburger buns, you get different coding.

    03:13 And you have a very specific sequence that makes up the protein.

    03:18 So the protein is the sort of the chain of blue circles there.

    03:22 Kind of like a string onion coming out of the hamburger.

    03:25 So that protein is very specifically configured based on the characteristics of the messengerRNA.

    03:32 Now the unchanged, sorry uncharged transferRNA is then discarded and eventually becomes charged and then it grabs another amino acid.

    03:43 Now, the drugs we're going to talk about act at different points in this 70 S ribosomal unit.

    03:50 So for example, chloramphenicol blocks the transpeptidation which is the joining of the two amino acids.

    03:57 The macrolides also block transpeptidation but in a slightly different area.

    04:03 The tetracyclines binds to 30 S subunit and prevent binding of incoming transferRNA.

    04:10 So they actually stop, you know transferRNA number 7 from joining.

    04:15 Linezolid has a unique site that inhibits initiation complex formation.

    04:21 So initiation complex is the very first reaction that brings the 30 S and the 50 S together.

    04:27 And allows everything to start working.

    04:29 On the other end of the production line there, the streptogramins block exit ports for polypeptides.

    04:36 So new ones can't come in and overall transcription is inhibited.


    About the Lecture

    The lecture Overview – Bacterial Protein Synthesis Inhibitors (Antibiotics) by Pravin Shukle, MD is from the course Antimicrobial Pharmacology.


    Included Quiz Questions

    1. They must act on the 50S subunit of the ribosome.
    2. They are always bactericidal.
    3. They include antibiotics such as tetracyclines and aminoglycosides.
    4. They involve a narrow therapeutic index.
    5. They are effective against a wide range of disease causing bacteria.
    1. Tetracyclines
    2. Chloramphenicol
    3. Linezolid
    4. Streptogramins
    5. Macrolides
    1. An agent that inhibits bacteria from replicating without necessarily killing them.
    2. An agent that kills bacteria upon exposure.
    3. An agent with increased killing activity with increased concentration.
    4. An agent whose activity is enhanced with increased duration of exposure.
    5. An agent whose effect lasts after the elimination of antibiotics from the body.

    Author of lecture Overview – Bacterial Protein Synthesis Inhibitors (Antibiotics)

     Pravin Shukle, MD

    Pravin Shukle, MD


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