How does antibiotic resistance work?

How does antibiotic resistance work?

 Resistance may be natural, that is, intrinsic to the microorganism in question, or it may be acquired.

Some bacteria are able to resist antibiotic action by denying it entry to the cell; penicillin G for example is unable to penetrate the Gram negative cell wall. Others can pump the antibiotic back out of the cell before it has had a chance to act, by means of enzymes called translocases; this is fairly non-specific, leading to multiple drug resistance. Other bacteria are naturally resistant to a particular antibiotic because they lack the target for its action, for example, mycoplasma do not possess peptidoglycan, the target for penicillin’s action.

To avoid the action of an antibiotic, bacteria may be able to use or develop alter-native biochemical pathways, so that its effect is cancelled out. Many pathogens can secrete enzymes that modify or degrade antibiotics, causing them to lose their activ-ity; we have already seen that penicillins can be inactivated by enzymatic cleavage of their β-lactam ring. Similarly, chloramphenicol can be acetylated, while members of the aminoglycoside family can be acetylated, adenylated or phosphorylated, all leading to loss of antimicrobial activity.

Mutations may occur which modify bacterial proteins in such a way that they are not affected by antimicrobial agents. You will recall that streptomycin normally acts by binding to part of the 30S subunit on the bacterial ribosome; the actual binding site is a protein called S12. Mutant forms of the S12 gene can lead to a product which still functions in protein synthesis, but loses its ability to bind to streptomycin. Similarly, mutations in transpeptidase genes in staphylococci means they do not bind to penicillin any more, so cross-linking of the cell wall is not inhibited.