Beta lactam antibiotics, such as penicillins and cephalosporins, have a beta-
lactam ring in their structure, which gives them their name.
These medications inhibit cell wall synthesis in bacteria. Unfortunately for us,
bacteria are becoming increasingly resilient to beta lactams, so we’ve come
up non-beta lactam medications to inhibit cell wall synthesis.
So, our body is made out of eukaryotic cells.
Bacterias belong to a different type of cells, called the prokaryotes.
From the outside to inside, they have a slimy capsule made out of
polysaccharides.
Then, there’s a cell wall in most prokaryotes.
A cell wall is a structural layer, which encapsulates bacteria, and offers
structural support and protection, like a suit of armor. It also offers some
filtering capabilities, as not everything can pass freely through it.
Finally, on the inside, there’s a pretty standard cell membrane.
Should something happen to this wall, say, if its synthesis mysteriously
stopped, its owner’s life expectancy will turn to that of a snowflake in
Sahara. And that’s exactly what we’re hoping to do.
Bacterial cell walls are made of a substance called peptidoglycan, or murein.
Peptidoglycan is a very strong, crystal lattice resembling three-dimensional
structure, composed out of long using “strands” of amino polysaccharides,
running in parallel.
These are made of made out segments of N-acetylglucosamine, or NAG, and
N-acetylmuramic acid, or NAM, in an alternating pattern - so, NAG, NAM,
NAG, NAM, and so on, like a pearl necklace.
These strands are also cross linked by short, four to five amino acids long, or
tetrapeptide chains, protruding from NAM subunits.
, Those pentapeptides reach out and link to pentapeptide chains from the
neighboring strands, for structural stability, a sub-process known as
transpeptidation.
All of this is made possible by enzymes called DD-transpeptidases, that are
also better known as penicillin binding proteins, or PBPs.
These enzymes are highly specialized to grab and hold two pentapeptide
ends and fuse them together, creating a stable link between the two
polysaccharide strands, essentially creating peptidoglycan.
If you imagine the enzyme as a “lock”, then the pentapeptide chain would be
a key, so it fits perfectly in, and allows the enzyme to do its work.
In essence, all beta lactam antibiotics, like the cephalosporins, somewhat
resemble the tetrapeptide chains.
Inside the bacteria, PBP enzymes will mistakenly bind to the beta lactams
antibiotic molecule instead of a tetrapeptide and stick inside the PBP forever,
like chewing gum in a keyhole, permanently disabling it.
As more and more of PBPs get disabled, the crosslinking fails to occur, and
the wall becomes weak and unstable.
If the affected bacteria attempts to divide, their cell wall will collapse, killing
them in the process!
Now, some bacteria have developed resistance to beta lactam antibiotics.
The most notable is the notorious staphylococcus aureus, which evolved an
enzyme called beta lactamases or penicillinases that breaks down the beta
lactam ring within the antibiotic, rendering it ineffective.
In response, we started adding beta lactamase inhibitors, such as clavulanic
acid, that would binding to beta lactamases and inactivate them, like the gum
into the keyhole.
lactam ring in their structure, which gives them their name.
These medications inhibit cell wall synthesis in bacteria. Unfortunately for us,
bacteria are becoming increasingly resilient to beta lactams, so we’ve come
up non-beta lactam medications to inhibit cell wall synthesis.
So, our body is made out of eukaryotic cells.
Bacterias belong to a different type of cells, called the prokaryotes.
From the outside to inside, they have a slimy capsule made out of
polysaccharides.
Then, there’s a cell wall in most prokaryotes.
A cell wall is a structural layer, which encapsulates bacteria, and offers
structural support and protection, like a suit of armor. It also offers some
filtering capabilities, as not everything can pass freely through it.
Finally, on the inside, there’s a pretty standard cell membrane.
Should something happen to this wall, say, if its synthesis mysteriously
stopped, its owner’s life expectancy will turn to that of a snowflake in
Sahara. And that’s exactly what we’re hoping to do.
Bacterial cell walls are made of a substance called peptidoglycan, or murein.
Peptidoglycan is a very strong, crystal lattice resembling three-dimensional
structure, composed out of long using “strands” of amino polysaccharides,
running in parallel.
These are made of made out segments of N-acetylglucosamine, or NAG, and
N-acetylmuramic acid, or NAM, in an alternating pattern - so, NAG, NAM,
NAG, NAM, and so on, like a pearl necklace.
These strands are also cross linked by short, four to five amino acids long, or
tetrapeptide chains, protruding from NAM subunits.
, Those pentapeptides reach out and link to pentapeptide chains from the
neighboring strands, for structural stability, a sub-process known as
transpeptidation.
All of this is made possible by enzymes called DD-transpeptidases, that are
also better known as penicillin binding proteins, or PBPs.
These enzymes are highly specialized to grab and hold two pentapeptide
ends and fuse them together, creating a stable link between the two
polysaccharide strands, essentially creating peptidoglycan.
If you imagine the enzyme as a “lock”, then the pentapeptide chain would be
a key, so it fits perfectly in, and allows the enzyme to do its work.
In essence, all beta lactam antibiotics, like the cephalosporins, somewhat
resemble the tetrapeptide chains.
Inside the bacteria, PBP enzymes will mistakenly bind to the beta lactams
antibiotic molecule instead of a tetrapeptide and stick inside the PBP forever,
like chewing gum in a keyhole, permanently disabling it.
As more and more of PBPs get disabled, the crosslinking fails to occur, and
the wall becomes weak and unstable.
If the affected bacteria attempts to divide, their cell wall will collapse, killing
them in the process!
Now, some bacteria have developed resistance to beta lactam antibiotics.
The most notable is the notorious staphylococcus aureus, which evolved an
enzyme called beta lactamases or penicillinases that breaks down the beta
lactam ring within the antibiotic, rendering it ineffective.
In response, we started adding beta lactamase inhibitors, such as clavulanic
acid, that would binding to beta lactamases and inactivate them, like the gum
into the keyhole.
