Tutorial: Penicillin: Part I responses

What is the history of penicillin?

Penicillin is a chemical compound derived from penicillium mould. It is thus a naturally occurring substance which is likely to have been in existence for millions of years. Alexander Fleming is attributed with the discovery of penicillin in 1928. Other scientists (Lister, Duchesne) made very similar findings years, even decades earlier. Fleming gets the credit however, probably because of his work in trying to purify the substance. He also gave the substance the name of penicillin.

Mass production of Penicillin was developed by Howard Florey and Ernest Chain during the late 1930’s and early 40s. By 1943, numerous patients were receiving penicillin, and it’s production was very much driven by WWII.


How does it work?

Penicillin works by interfering with bacterial cell wall synthesis, and in particular the cross linking of peptidoglycan within the cell wall. In more detail, the beta-lactam part of the penicillin molecule binds to the enzyme transpeptidase that is responsible for linking the peptidoglycan molecules in bacteria.

It has a synergistic effect with aminoglycosides because it weakens the cell wall, facilitating the entry of gentamicin which exerts it’s antibacterial effect by inhibiting protein synthesis.


What is the difference between a penicillin antibiotic and a Beta-lactam antibiotic?

This is a question of semantics….

Penicillin antibiotics are generally recognised to include benzylpenicillin (penicillin G), phenoxymethypenicillin (penicillin V), amoxicillin, ampicillin, cloxacillin, dicloxacillin, flucloxacillin and piperacillin (amongst others)

Beta-Lactam antibiotics all contain a beta-lactam ring. All penicillins are beta-lactams.

Beta-Lactam antibiotics in addition to penicillins also include cephalosporins, monobactams and carbapenems, which all contain a beta-lactam ring.


How does penicillin resistance arise?

Bacterial resistance mechanisms can be as complex as you want them to be. Put most simply, there are three ways a bacterium can be resistant to an antibiotic. It can..

  1. Prevent the antibiotic getting in/refuses entry.
  2. Get the antibiotic out.
  3. Destroy the antibiotic.


For example :

Staph. aureus may be resistant to penicillin by containing a beta-lactamase (destroy the antibiotic)

Staph. aureus may be resistant to flucloxacillin by containing a gene (MEC A) encoding for a penicillin binding protein (PBPIIA)which does not bind flucloxacillin and thus refuses entry. (MRSA)


The more you know about antibiotic resistance, the more complex it gets…!, but this will do for now.




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