Overview – Bacterial Protein Synthesis Inhibitors (Antibiotics)

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 50S 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 30S 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 30S 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 70S ribosomal mRNA subunit is composed of a 50S and a 30S.

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 50S and the 30S make up 70S 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 70S ribosomal unit.

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

02:15 Now, this is a hamburger.

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

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

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

02:24 The 50S 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 70S 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 30S 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 30S and the 50S 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 translation is inhibited.