Mechanisms of antibiotic resistance

Definitions & Key takeaways

The mechanisms of antibiotic resistance can be broadly classified into four categories. First, there is enzymatic modification of the antibiotic includes beta-lactamases, which cleave the beta-lactam ring in penicillins and cephalosporins, and other (e.g. AmpC) enzymes, which hydrolyze most beta-lactams except.

The second mechanism of antibiotic resistance is alteration of the target site on the bacterial cell wall. This involves the production of altered penicillin-binding proteins (PBP), which decrease the affinity of the antibiotic for its target.

Third, bacteria may use efflux pumps, which prevent a variety of antibiotics from accumulating in the bacteria cell, by pumping them out of the bacterial cell. Finally, since some antibiotics (e.g. sulfonamides) work by inhibiting the synthesis of molecules that are vital to the bacteria survival like folic acid, bacteria may just stop producing these molecules, and scavenge for folic acid from the environment instead.

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The discovery of antibiotics is one of the most important advancements in clinical medicine and public health. It has laid the foundation for a number of other advancements including the ability to perform surgeries more safely and reduction of infant and maternal mortality rates.Many antibiotics are derived from other bacteria or fungi.
For example, penicillin, secreted by the fungus Penicillium, can kill bacteria. This is because microbes use antibiotics to fight off other microbes.
But the use of antibiotics, and, more broadly, antimicrobials, which includes medications that target not only bacteria, but also viruses and fungi, has exploded in recent years.
Antimicrobials have been used on an industrial scale, partially because of overprescription in humans, but more so because of routine use in farm animals!
In fact, a good number of antimicrobials are excreted from humans and animals unchanged, and these get flushed into waste water, which allows pathogens to be perpetually exposed to antimicrobials.
In response to this enormous selective pressure, many pathogens have become highly resistant to antimicrobials.Now when it comes to bacteria, generally speaking, there are four mechanisms for how they become resistant to antimicrobials.
The first mechanism is antibiotic inactivation or modification, which is where bacteria develop specific enzymes that destroy and inactivate antimicrobials.
One example is beta lactamase, which is a bacterial enzyme that destroys antimicrobials that contain a beta lactam ring, like penicillins and cephalosporins.
As a result, bacteria that produce beta lactamases are immune to the action of many beta lactam antibiotics.The second mechanism is the alteration of a target, or binding site.
An antibiotic that cannot bind anywhere is rendered useless. One example is methicillin-resistant Staphylococcus aureus, or MRSA which modifies its penicillin binding locations, making them unable to be bound by antibiotics in the penicillin family.The third mechanism is bypassing metabolic inhibition.
For example, some antibiotics, such as sulfonamides, disturb the metabolic pathway that synthesizes folic acid, which is vital to DNA-based organisms.
But to get around this, some bacteria are able to scavenge for folic acid from the environment, completely circumventing the action of sulfonamides.The fourth mechanism relies on preventing antibiotic accumulation.
One way that bacteria do that is by decreasing the permeability of their membrane to the antibiotic. The other way is to create efflux pumps, which pump the antibiotic out of the bacteria.
Both actions result in lower intracellular antibiotic concentrations - reducing or even negating the effect.Now, these mechanisms work in different organisms against different antibiotics.
It’s an ongoing challenge - for every new antibiotic that’s identified, pathogens rely on selection pressure to find a mutation that somehow allows them to thrive in the presence of that antibiotic.
All right, as a quick recap. Bacteria can achieve antibiotic resistance through four fundamental mechanisms.
Inactivation physically destroys the antibiotics before they can do their job. Alteration of the binding site leaves the antibiotic without a binding site, and therefore unable to work.
Alteration of a metabolic pathway completely bypasses the activity of the antibiotic. Finally, reduction of accumulation keeps the intracellular levels