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What is antibiotic resistance?

Bacteria
Antibiotic resistance describes a bacteria’s ability to survive while being exposed to antibiotics.

How does antibiotic resistance develop exactly?

When a bacteria is exposed to antibiotics there are three possible outcomes - they will die, they will stagnate (not multiply), or they will multiply. Three main factors will predict which is more likely to happen; antibiotic concentration, bacterial mutation, and bacterial genetic exchange.
Antibiotic concentration
Generally, the more antibiotic getting to a bacteria will cause it to stagnate/die, and less antibiotic will allow it to multiply. Some bacteria live within a “biofilm”, which is a jelly-like substance where thousands of bacterial cells are suspended inside (think raspberry seeds in raspberry jelly). It’s sort of like a big, thick energy shield. The antibiotic has to move (diffuse) through the biofilm to reach all of the bacterial cells. Some cells that are buried deep within the biofilm are exposed to only a fraction of the antibiotic that reaches the surface.
Antibiotics traveling through biofilm
Bacterial mutation
When bacterial cells replicate, there is a small chance the new bacterial cell will not be exactly the same as the original bacterial cell. We call these errors in the copied cell a mutation. In one bacterial cell, the cell wall could be slightly different, in another an enzyme works poorly, and so on. Mutations are key to the idea of evolution, and all of the diversity you can see in nature came from a series of many mutations over hundreds of thousands of years. In animals, it can take centuries or millennia for a species to adopt a mutation which helps it survive (and sometimes these mutations create entirely new species). It takes this long in animals because it takes years for most animals to grow up and reproduce.
Bacteria on the other hand can multiply within hours, allowing for more mutations to occur over a shorter period of time. These mutations (such as a change to the bacteria’s cell wall) can make it difficult for the antibiotics to enter the bacteria or stick to it, making the antibiotic less effective at hurting or killing the bacteria.
There are four common mutations bacteria undergo to become resistant to antibiotics:
  1. Enzymes in the bacteria eat and deactivate antibiotics.
  2. Antibiotics are ejected from the bacteria.
  3. The bacterial wall prevents antibiotics from entering.
  4. The bacteria adopts a new way of processing energy (as some antibiotics interfere with the energy process).
Bacterial mutations to fight antibiotics
These little mutant bacteria may thrive where the non-mutant bacteria die, and new antibiotics (or more of the same antibiotic, if the mutants are only slightly resistant) must be used to kill them.
Humans continue to search for new antibiotics to help the immune system, and bacteria continue to have mutant members in their colonies that can potentially resist antibiotics!
Bacterial genetic exchange
A curious habit of bacteria is that they love to share information when they meet, like two old friends at the park. This happens even between two different bacterial species. As a result, once a single bacterial species has managed to resist antibiotics with a gene(s), that gene(s) can get copied and passed around to other bacteria. It’s like passing around a juicy bit of gossip - as more meetings occur, more and more bacteria learn how to resist an antibiotic!

How do we measure antibiotic resistance?

In order to pick the best antibiotic for treating the infection, its useful to know how effective the antibiotic would be at preventing a bacteria from growing or simply killing the bacteria. You can do an experiment to figure it out! You can even see how resistant bacteria is to antibiotics by running the same experiment multiple times using a variety of antibiotics.
Finding MIC and MAC
Step 1:
Place a tiny but equal amount of bacteria into a series of test tubes full of clear, nutritious bacterial broth (chicken soup for the bacteria!). Next, put increasing amounts of antibiotic into the test tubes (doubling the antibiotic concentration as you go). Now wait 24 hours.
1. Some of the tubes have turned cloudy! The concentration of the antibiotic in these tubes are too low to prevent the bacteria from multiplying.
2. Some of the tubes are still clear! The concentration of the antibiotic in these tubes are high enough to prevent the bacteria from multiplying. The lowest concentration of an antibiotic needed to stop bacteria from multiplying is called the Minimum Inhibitory Concentration (MIC). In the diagram above, the MIC is the first clear test tube. But wait! Are the concentrations of the antibiotic in these clear tubes enough to kill the bacteria or just stop them from multiplying? We can find out!
Step 2:
Take a small sample of fluid from each of the clear test tubes in step 1 and put each sample into a new test tube filled with broth. Do not put antibiotics in these new test tubes. Once again wait 24 hours. Note: There will be a bit of antibiotic carried in the sample from step 1, however not enough to affect the results in step 2.
3. Some of the test tubes have turned cloudy! The bacteria is growing again! This means the concentration of the antibiotic in step 1 didn't kill the bacteria, just stopped it from multiplying.
4. Some of the test tubes are still clear! This means the concentration of the antibiotic in step 1 killed the bacteria. The lowest concentration of an antibiotic needed to kill the bacteria is called the Minimum Bactericidal Concentration (MBC). In the diagram above, the first clear test tube in step 2 is the MBC.
Once you know the concentration of an antibiotic needed to stop a bacteria from growing (MIC) or living (MBC), you need to know whether that concentration can be safely given to a person. If so, then we would say that a bacteria is “susceptible” to an antibiotic, and if not, then we would say that a bacteria is “resistant” to an antibiotic. The goal is to pick an antibiotic that will be effective against the bacteria causing an infection, but won’t hurt a patient or destroy their healthy ecosystem of bacteria.

How resistant have pathogens become?

Antibiotic resistance of pathogens graphed over time
Over the years some bacteria have become more resistant to antibiotics than others. Here’s a quick glance at some of the most common and/or concerning resistant bacteria:
  • Carbapenem-resistant enterobacteriaceae (CRE): Some strains of CRE are incurable and are resistant to all antibiotics. Patients who have bloodstream infections with CRE have a mortality rate of 50%. While these infections are rare, researchers are very concerned about the spread of CRE.
  • Clostridium difficile (C. difficile): This bacteria usually invades after antibiotics have ruined the normal bacterial ecosystem of the gut, and can cause symptoms like painful, bloody diarrhea and fevers. It’s often found in hospitals and group homes, and frequently is fatal for the elderly. This bacteria is naturally resistant to many antibiotics and generates spores that are particularly tough to kill. 
  • Neisseria gonorrhoeae: This bacteria is the cause of the second most common infection (Gonorrhoeae) in North America and can lead to serious reproductive complications. While at one time it was thought to be extremely easy to treat, now ~30% of infections are resistant to an antibiotic.

How do you prevent bacteria from developing antibiotic resistance?

To limit antibiotic resistance, it’s important to limit the exposure that bacteria all over the planet (inside of us, within animals, and living in the environment) have to antibiotics. two ways you can help make sure bacteria are not getting overexposure to antibiotics are:
  • Taking antibiotics responsibly: Take antibiotics only if you have a bacterial infection (not a virus), and pick one that is narrow spectrum so that it doesn’t kill off your healthy bacterial ecosystem. Ask your healthcare professional to help you make these choices. Similarly for animals - narrow spectrum antibiotics should be used to treat bacterial infections, rather than indiscriminate use among healthy animals. Being really selective in how we use antibiotics keeps them from becoming obsolete. 
  • Trash antibiotics responsibly: Disposal of antibiotics should be done in a way that minimizes the exposure of bacteria living in the environment to the antibiotic. For example, you shouldn’t crush antibiotics or flush them down the toilet. That gives the antibiotics direct access to bacteria living in the soil and water. Instead, two options are to either give them back to a pharmacist for disposal or to put them into a sealed plastic bag and toss it into the trash.

References
Silver, L. L. (2011). Challenges of Antibacterial Discovery. Clinical Microbiology Reviews, 24(1), 71–109. doi:10.1128/CMR.00030-10

Want to join the conversation?

  • blobby green style avatar for user jenelle.sisopha
    As the development of new antibiotics and antibiotic resistance is a growing international concern, why don't scientists and doctors steer their research towards the enhancement of the human immune system? Perhaps a simple upgrade can be achieved through placing greater emphasis on nutritional intake, exercise and outdoor involvement in the natural world. But what I'm talking about is a much superior advancement. For instance, households with domestic animals experience an increase in immunity, or in other words, generally have stronger immune systems relative to families who do not - which is as a result of being subject to a more sufficient level of bacterial exposure. Furthermore, if animals have significantly stronger immune systems, does this not support the understanding that an 'elite' defence system exists, and that the human immune system has not yet reached the pinnacle of its potential? Another huge question is, what potential DO we have? What ARE the possibilities? In advance, thank you for your time! :)
    (13 votes)
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    • male robot johnny style avatar for user jon.email
      Keep in mind that having a "stronger" immune system isn't a good thing. Our immune system has a very uneasy balance inside our bodies. If it's too slow or weak, we get sick and could die. But if it's too strong or too fast, we get allergies... or worse, an autoimmune disease, where our immune cells get overzealous and start destroying our own cells.

      There's even research showing that a stronger immune system might cause more cellular damage over time, accelerating aging. So someone might get sick less often, but end up dying sooner because their body wears out from their immune system causing damage!
      (31 votes)
  • aqualine ultimate style avatar for user mhth766
    Question from the graph - what caused the decided dip in anti-biotic resistance in the late 90s/early 00s?
    (7 votes)
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  • aqualine tree style avatar for user Alaka Panigrahi
    i have a doubt. now if many bacterial cells invade my body, i will opt for broad spectrum antibiotic. but will this work against my healthy e.coli bacteria and disrupt it?
    (5 votes)
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    • leafers ultimate style avatar for user Phill Spence
      Absolutely and it does all the time. Antibiotics will damage your local flora which can cause anything from gas to diarrhea to yeast infections in women. Many clinicians now recommend you consume active culture yogurt while on antibiotics to replace the gut bacteria that are being killed off.
      (8 votes)
  • mr pants teal style avatar for user Janet Still
    Why does taking antibiotics when one has a viral illness (first bullet point in the last section), or something else not bacteria-related, contribute to antibiotic resistance? How can the bacteria become resistant in the future when it did not exist when taking the medication in the first place?
    (1 vote)
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    • leaf green style avatar for user Joanne
      http://www.cdc.gov/drugresistance/about.html
      Some bacteria did exist and were present when the person took the antibiotics while sick with a viral infection. Sometimes we get antibiotics even though they can't really shorten a virus because the doctor wants to help prevent an additional or secondary infection by a bacteria (the cold might become pneumonia) . But the antibiotics kill susceptible bacteria and select for bacteria that can multiply in the face of this drug. Now we have a stronger bacteria that will multiply and make more of these super bugs. So, when they do cause a disease, they will not be killed by that antibiotic. Bacteria are on us and in us and are helpful to us, but using antibiotics when they are not necessary selects for a genetically changed population of bacteria. For example, they might now have a gene that codes for an enzyme that destroys that antibiotic. They can also share that gene for the enzyme with different bacteria using a plasmid and then those new bacteria that were not present during the cold would also have this enzyme. Yikes! The best analogy is war secrets, like a fighter jet . If the potential enemy gets to see the fighter jet before a real war, they can build a defense against it so the weapon will be useless and they can give this new secret defense to their friends. Follow the link for more examples from the CDC.
      (12 votes)
  • duskpin ultimate style avatar for user Gabriela Vianna Valente
    When they talk about the common mutations bacteria undergo, it says "enzymes in the bacteria eat and deactivate antibiotics". I'm not an English native speaker, so I don't know what is the word to use when talking about the mechanisms of enzymes. Is "eat" is really that specific word or was it used only for it to be more easily undestood?
    (2 votes)
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  • piceratops tree style avatar for user Gautham Gopinath
    When referring to how antibiotic resistance occurs, what does the phrase, "selective pressure" mean? How could selective pressure lead to antibiotic resistance occurring?
    (2 votes)
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    • leaf green style avatar for user Joanne
      'Selective pressure' is any phenomenon in an environment that has an effect on a species' s fittness or ability to survive in that environment. Because this phenomenon is present, certain organisms or animals are selected because they can survive and reproduce in that environment. Taking antibiotics changes the human environment, killing susceptible microbes and therefore also selecting microbes that continue to live despite that antibiotic. Those surviving microbes are resistant to the drug.
      (4 votes)
  • spunky sam blue style avatar for user Omkar Patil
    so do we have to make more and more powerful antibiotic every time .
    (3 votes)
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  • male robot donald style avatar for user Arnav Nanavati
    What happens when you take antibiotics when not needed?
    (2 votes)
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    • aqualine ultimate style avatar for user Sterre
      This is actually a really big issue and should be prevented as much as possible. If you take antibiotics when not needed (or don't finish a prescription) bacteria in your body can develop resistance to it. This can put you, and others, in danger when you actually need to be treated and all of a sudden these drugs don't work anymore.
      (2 votes)
  • sneak peak yellow style avatar for user Amogha
    Suppose I use antibiotic "A" for such a long time that the bacteria become completely resistant to the antibiotic and then switch to a completely different antibiotic "B",how long would I have to wait until the bacteria "discards" the genes that are resistant to "A" to start using it again?
    (2 votes)
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  • hopper cool style avatar for user Madeliv
    "A curious habit of bacteria is that they love to share information when they meet" How do they know which information to share? They might have a "useless" mutation, so how do they know when it is beneficial to exchange and retain information?
    (1 vote)
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    • leaf green style avatar for user Joanne
      You are correct, the information may not be beneficial. But let us consider if the information is beneficial, then what happens? Correct, that cell and the receiving cell live longer. What do they do when they live longer? They share that beneficial genetic information with more bacteria. Then what happens? More cells in the bacterial population have this characteristic of being able to survive an antibiotic or whatever the beneficial characteristic provides. Cells that do not have this characteristic die when exposed to the drug, so we say the drug is an artificial selection pressure on the population of bacteria. They do not "know" what is beneficial but they have several methods of transferring genetic information themselves and bacterial viruses can also move genes, so the possibility of one or more bacterial populations evolving quickly is great given the fact that their generation time may be a couple of hours. Even if they did not share the genetic info, if they began dividing where one cell becomes 2 cells, 2 becomes 4 etc, then in a day or so you can have millions of that bacteria and that is yet another thing bacteria do when they live longer and food is plentiful. Again the resulting population is made up of resistant bacteria.
      (2 votes)