Cell wall synthesis in bacteria is a low host toxicity target, so a good target because humans do not have peptoglycan. The vast majority of the cell wall targeting antibiotics have a structural component called the beta-lactam ring that we can see here. And these beta-lactam drugs include the penicillins and the cephalosporins.
Penicillin G. was the first beta-lactam antibiotic that was characterized and isolated from the penicillium chrysogenum fungus by Alexander Fleming. And that happened in 1929. However, it was really difficult to isolate and Fleming failed in convincing anyone that his discovery was important, which is really interesting. So from 1929 to 1940, nothing was done with penicillin.
It wasn't until 1940, an Australian scientist called Howard Florey and his colleagues made progress in isolating the antibiotic that its functionality and its place in history was really rounded. Penicillin G is primarily active against gram-positive bacteria, particularly streptococci and pneumococcal infections. However, it's not really effective against gram-negative.
It can actually pass across the outer membrane. It's impermeable to this substance. So from the stock of penicillin, from penicillin G, we've made a number of semi-synthetic penicillins, and these differ by their side groups. So if you look, this is penicillin G here, and you can see these side groups now differ. And because they differ, some of them can now be transported across the outer membrane and are therefore effective against gram-negative bacteria.
The beta-lactam antibiotics are analogs of the terminal amino residues on the precursor pentapeptide glycan subunits. So remember these from our previous lectures where the pentapeptide was transported by Bactoprino across the membrane where these were then inserted into that backbone while this cell was dividing. So they have structural similarity to these pentapeptides. This structural similarity then facilitates their binding to the active site of these peptidases, these transpeptidases, which are also known as penicillin binding proteins or PBPs because of their affinity for those beta-lactam antibiotics. So when they bind to these transpeptidases, that prevents the cross-linking, the final cross-linking happening.
So the transpeptidization step doesn't happen and that disrupts this whole cell wall synthesis. And when these penicillin binding proteins bind penicillin, they cannot catalyze that reaction at all. Cell wall is no longer cross-linked.
And that means that that cell wall is now compromised. Penicillin also stimulates the release of autolycins, which are going to further digest the existing cell wall, enhancing their activity. And ultimately, what will happen is we will have a weak self-degrading cell wall and the osmotic pressure inside of this cell will cause the cell to eventually lies open