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.