Understanding penicillin resistance
So, how do bacteria develop resistance against β-lactam penicillins?The mode of action of penicillins depends greatly on the presence of the β-lactam ring. This structure produces a molecular ‘key’ that is able to interact with the active site ‘lock’ of the transpeptidase enzyme; disrupting its ability to create peptidoglycan crosslinks in the bacterial cell wall.
Bacteria can use β-lactamases to break open the β-lactam ringJust as β-lactam rings can interfere with the activity of enzymes, so they can also be cleaved through enzymatic activity. Enzymes called β-lactamases can catalyse opening of the β-lactam ring through reaction with water, in a hydrolysis reaction. In earlier sections we have seen that hydrolysis gives a penicilloic acid, which is not antibacterially active and is readily excreted from the body once produced.
Designing penicillins that resist being inactivated by β-lactamasesMany bacterial species can synthesise their own β-lactamases which will target and disable penicillins. Penicillins themselves can be modified to provide some protection against these enzymes. For example, in methicillin, a bulky substituted benzene (at the variable R site of the penicillin molecule) provides a steric hindrance to any enzymes that try to interact with the β-lactam ring of the penicillin. Despite this there have been classified strains of methicillin resistant Staphylococcus aureus or MRSA since the 1960s, which have developed through the over-prescription of methicillin and related penicillins. As such, bacterial resistance to penicillins still remains a serious concern to the medical world.
Bacteria can become resistant to penicillin by modifying enzymes that make the cell wallSome bacteria, including Streptococcus phenominae, have developed resistance to β-lactams through modification of their penicillin binding proteins (or PBPs), which make up the active site of transpeptidase enzymes. Where normally β-lactams react with PBPs to form a relatively stable ring-opened product, mutations in the genetic coding for proteins making up the transpeptidase enzyme can result in multiple PBPs that have a low binding affinity for β-lactams. As such our β-lactam ‘key’ no longer fits into the transpeptidase active site ‘lock’. Penicillins do not bind as effectively to their target PBPs and the transpeptidase enzymes continue to function, binding to their original substrate rather than the antibiotic.
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Exploring Everyday Chemistry
Come cleanTriclosan is an antibacterial ingredient added to soaps and body washes, toothpastes, and some cosmetics. In toothpastes, for example, it is effective against gum disease. Research has shown that low concentrations of triclosan can lead to resistant E. coli bacteria becoming the more dominant strains more likely to survive and reproduce. So, low concentrations in everyday products like toothpastes and body washes could lead to the development of antibiotic-resistant bacteria. There is also largely a lack of evidence for additional benefits of products labelled as ‘antimicrobial’ over traditional cleaning and hygiene products (e.g. bleach, soap and water). This has led to a ban across the EU and USA in its use in hygiene products (hand, skin and body washes), although many other antimicrobial agents are still used in these products.You may also be surprised to find antimicrobials in household products ranging from craft supplies (like markers and scissors) to food storage containers, kitchenware (e.g. cutting boards), paints, textiles and toys. However, in such products, manufacturers are not required to tell us what makes their products antimicrobial and so it can difficult, if not impossible, to find out exactly which products contain which antimicrobials!
Exploring Everyday Chemistry
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