How do bacteria become resistant to antibiotics?

Antibiotics are compounds that either:

  1. kill bacteria directly (bacteriocidal)
  2. hamper their ability to grow and reproduce (bacteriostatic)

When you are fighting off a bacterial infection, your immune system can be overwhelmed by the invading bugs. Antibiotics are thrown into the fray to mount a defense against the invaders until your immune system can recover and finish off the remaining bacteria.


How do antibiotics stave off bacterial growth? Antibiotics stop or interfere with a number of everyday cellular processes that bacteria rely on for growth and survival, such as:

  • crippling production of the bacterial cell wall that protects the cell from the external environment
  • interfering with protein synthesis by binding to the machinery that builds proteins, amino acid by amino acid
  • wreaking havoc with metabolic processes, such as the synthesis of folic acid, a B vitamin that bacteria need to thrive
  • blocking synthesis of DNA and RNA

Antibiotics stop working because bacteria come up with various ways of countering these actions, such as:

  • Preventing the antibiotic from getting to its target When you really don't want to see someone, you might find yourself doing things like hiding from them or avoiding their phone calls. Bacteria employ similar strategies to keep antibiotics at bay. One effective way to keep a drug from reaching its target is to prevent it from being taken up at all. Bacteria do this by changing the permeability of their membranes or by reducing the number of channels available for drugs to diffuse through. Another strategy is to create the molecular equivalent of a club bouncer to escort antibiotics out the door if it gets in. Some bacteria use energy from ATP to power pumps that shoot antibiotics out of the cell.
  • Changing the target Many antibiotics work by sticking to their target and preventing it from interacting with other molecules inside the cell. Some bacteria respond by changing the structure of the target (or even replacing it within another molecule altogether) so that the antibiotic can no longer recognize it or bind to it.
  • Destroying the antibiotic This tactic takes interfering with the antibiotic to an extreme. Rather than simply pushing the drug aside or setting up molecular blockades, some bacteria survive by neutralizing their enemy directly. For example, some kinds of bacteria produce enzymes called beta-lactamases that chew up penicillin.

How do bacteria pick up these drug-fighting habits? In some cases, they don't. Some bacteria are simply making use of their own inherent capabilities. However, there are many bacteria that didn't start out resistant to a particular antibiotic. Bacteria can acquire resistance by getting a copy of a gene encoding an altered protein or an enzyme like beta lactamase from other bacteria, even from those of a different species. There are a number of ways to get a resistance gene:

  • During transformation - in this process, akin to bacterial sex, microbes can join together and transfer DNA to each other.
  • On a small, circular, extrachromosomal piece of DNA, called a plasmid - one plasmid can encode resistance to many different antibiotics.
  • Through a transposon - transposons are "jumping genes," small pieces of DNA that can hop from DNA molecule to DNA molecule. Once in a chromosome or plasmid, they can be integrated stably.
  • By scavenging DNA remnants from degraded, dead bacteria.

Unfortunately, if a bacterium gets a resistance gene stuck into its chromosomal DNA or picks one up in a free-floating plasmid, all of its progeny will inherit the gene and the resistance it confers. Why do resistance genes persist and spread throughout bacterial populations? It's basically just Darwin's idea of the survival of the fittest, reduced to a microscopic level -- bacteria with these genes survive and outgrow susceptible variants. And our own less than judicious use of antibiotics actually selects for these resistant types! Here's how we contribute to the problem:

  • Ignoring the brightly colored labels on the pill bottle and the doctor's admonitions to take all of the medicine that you get, even if you start to feel better. If you stop taking your medicine too early, your immune system may not be capable of killing off the stragglers, and any resistant bacteria left unscathed will be able to proliferate and spread to other people.
  • Insisting on getting antibiotics from the doctor to treat a cold or the flu. Antibiotics are completely ineffective against viruses, so you actually accomplish nothing by popping a pill. Worse yet, antibiotics can't discriminate between bacteria that are good for us and bacteria that cause disease. Our preoccupation with cleanliness notwithstanding, we actually peacefully co-exist with a wide variety of bacteria each day. For example, our intestines are lined with bacteria that break down foods that we can't digest. Whenever you take antibiotics, you kill off some of these beneficial bugs. Using antibiotics indiscriminately can blow away most of the bacteria normally in your body, opening the door for more sinister strains to establish themselves in their place.
  • Stockpiling leftover antibiotics and trying to medicate ourselves - not every antibiotic will work for every infection. Your doctor prescribes a specific drug for you based on what kind of infection you have. He or she also selects a specific dose and length for your treatment. The old antibiotic you have may not work at all against the infection you have, so it's best to seek a doctor's advice before trying to treat yourself.

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