way which stops the antibiotic reaching its target, or which stops it from functioning normally at its target. The antibiotic can be stopped from reaching its target by, for example, modifying the cell wall of the bacterium to make it impermeable to the antibiotic, and therefore stop it from being able to get inside the bacterium, as seen in figure 2.
Modification of the drug target is an example of a way to stop the normal function of an antibiotic; if the antibiotic carries out its function by binding to a specific shaped region in the bacterium, then changing the shape of this region will stop the normal function of the antibiotic. This can be better understood with a lock and key model, where the antibiotic is a key and the binding region is the lock; if the lock is changed then the key will no longer work as it is the wrong shape to open the lock.
Figure 2 shows one method of inactivating an antibiotic, which is to change its structure by adding a phosphate group. This impairs the normal function of the antibiotic, which would be to bind to the ribosomes of the bacterium, and affect the bacterium’ s ability to produce proteins, which it needs in order to survive.
The mechanisms described above are all possible due to alterations in the DNA of the bacterium, known as mutations( Benveniste and Davies, 1973). The DNA is the code to make proteins. For example, to modify the cell wall as in figure 2, the DNA mutates so that it codes for the new, modified cell wall protein, which causes its impermeability, instead of the normal cell wall protein, which is permeable.
There are different types of mutation, but figure 3 shows an insertion mutation, where extra DNA is inserted into the bacterium’ s existing DNA( U. S. National Library of Medicine, 2020). In figure 3 the DNA is shown to code for a sequence of amino acids, which are the the building blocks of a protein.
In the lower DNA strand the insertion of the nucleotide has clearly changed the amino acid sequence, where the alterations are shown in orange. From this it can be seen how changes in the bacterial DNA can indirectly lead to the development of antibiotic resistance in bacteria.
What makes‘ Superbugs’‘ super’?
Penicillins are a group of antibiotics that impair the ability of bacteria to repair their cell wall, the outer covering that protects all the internal structures of the bacteria. Penicillins, which include methicillin, are part of a wider group of antibiotics known as β-lactams. The example of MRSA is better adapted for resistance to β-lactams than non-superbug types of SA.
In SA and MRSA, transpeptidases, also known as penicillin-binding proteins( PBPs), are either partly or fully responsible for cell wall formation. For β-lactams, PBPs are good targets as they are essential for cell wall repair, and for bacterial survival. SA has four PBPs; MRSA has the same four PBPs, but it also has a fifth, PBP2a. Figure 4 shows the difference between PBPs in SA, and PBP2a; in A, PBP2 is seen to have a binding region for the β-lactam, which PBP2a does not, preventing the antibiotic from functioning normally. MRSA can then proceed to inactivate the β-lactam, as in B.
PBP2a is still able to continue functioning close to normally in the presence of β-lactams, where the functions of the other four PBPs would be severely impaired. This means that MRSA can sustain cell wall repair when β-lactams are used, while SA cannot. The capability to produce PBP2a is unique to MRSA, and the production gene was acquired from another, non-SA organism( Chang et al., 2014).
Superbugs have a particularly high ability to infect a patient and to spread rapidly. Of hospital based SA infections, many are caused by MRSA, which is antibiotic resistant, meaning it has resistance to more than one antibiotic; a number of MRSA kinds are resistant to most commonly used antibiotics( Foster, 2004). Several other bacteria have also been classified as being resistant to multiple antibiotics( Bajpai et al., 2017).
Until recently, MRSA had remained sensitive to the antibiotic vancomycin, but subsequently the bacteria developed low levels of resistance to the drug; MRSA now has, however, developed high levels of vancomycin resistance due to the transfer of resistance genes to SA from another kind of bacteria known as Enterococcus( Foster, 2004).
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