Understanding antibiotic resistance
Understanding antibiotic resistance

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Understanding antibiotic resistance

2.1 Inhibitors of cell wall synthesis

As you saw in Activity 2, the cell wall is essential for normal functioning of the bacterial cell. Antibiotic inhibitors of cell wall synthesis block the production of peptidoglycan, the main component of the cell wall. Cross-linking between peptidoglycan chains forms a strong, mesh-like structure that gives the cell wall structure and rigidity, and protects the underlying cell membrane from osmotic damage when water moving into the cell by osmosis could cause it to burst, or lyse. Disruption of the peptidoglycan layer of the cell wall can therefore result in cell lysis (Figure 3).

Described image
Figure 3 Lysis of a bacterium with a defective cell wall. (a) Diagram showing the sequence of events that lead to lysis. (b) Light micrograph of S. aureus: a lysed cell on the left and an intact dividing cell on the right.

Examples of cell wall synthesis inhibitors are the ß-lactam antibiotics. These include penicillin and its derivatives, and the cephalosporins. All ß-lactam antibiotics contain a core chemical structure called a ß-lactam ring (Figure 4) which determines the mode of action of this class of antibiotics.

Described image
Figure 4 Core ring structures of two types of β-lactam antibiotics. The β-lactam ring is shaded pink in each case.

The ß-lactam antibiotics interfere with the formation of the peptidoglycan cross-links, thereby weakening the cell wall. You will learn more about the precise mechanism in this week’s case study (Section 3). For now, you can see the effect of the disrupted cell wall on bacterial growth in Video 3.

Download this video clip.Video player: Video 3
Skip transcript: Video 3 A ß-lactam antibiotic in action.

Transcript: Video 3 A ß-lactam antibiotic in action.

This is cephalosporin C, the first compound in one of the most important classes of beta-lactams-- the cephalosporins. It occurs in nature and was originally isolated from a fungus found growing in a sewage outlet in Sardinia in 1947. It's the lead compound from which a whole family of antibiotics has been made, but it isn't itself a particularly powerful antibiotic. Why? It all hinges in the way that antibiotics work. What they do is disrupt the process of cell wall biosynthesis. In a growing colony, this process is taking place all the time, both to maintain the existing cell wall and to make new wall as the bacteria divide.
When an antibiotic is added to a colony, this inhibitory action has two effects. Firstly, the bacteria are prevented from successfully dividing, so they start to form long, spaghetti-like strings. The other effect arises from the fact that the existing cell walls routinely break down and are in constant need of repair. As the process of repair is prevented, small flaws appear, large enough to allow water to start moving into the cell due to the high internal osmotic pressure. As a result, the cells start to swell and eventually burst, a process called lysis.
End transcript: Video 3 A ß-lactam antibiotic in action.
Video 3 A ß-lactam antibiotic in action.
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