How do antibiotics know where to go?

[sameeralord]

Hello everyone,

Let's say I have a throat infection and all the bacteria are near the throat. I get antibiotics. So if these antibiotics enter bloodstream, how do they know they have to diffuse out right near the throat area. Are they diffusing all the time, going to unwanted places. Why is it bad to get antibiotics frequently, I can understand they will kill good bacteria, but how does this create antibiotic resistance to bad bacteria. Thanks

 

[TubbaBlubba]

Well, I can answer your last question.

In a bacterial colony, there will always be a few bacteria with mutations that make them immune to the antibiotics (for instance, they might have slightly different protein receptors of some sort). If you kill the rest with antibiotics, only the immune bacteria will replicate, thus creating a new, mostly immune bacterial stem.

 

[zomgwtf]

Hello everyone,

Let's say I have a throat infection and all the bacteria are near the throat. I get antibiotics. So if these antibiotics enter bloodstream, how do they know they have to diffuse out right near the throat area. Are they diffusing all the time, going to unwanted places. Why is it bad to get antibiotics frequently, I can understand they will kill good bacteria, but how does this create antibiotic resistance to bad bacteria. Thanks

Well, one thing to remember is that when you have an infection it may seem like it is localized in just your throat but it could be throughout many other areas of your body. Especially if it's gone to the point that you need to take antibiotics.

Now, what the antibiotics will do is just go around and whenever they meet bacterial cells they will destroy them. They do this in many ways but I believe the most frequent form is by altering/destorying the cell wall formation or structure, which of course kills the cell. This happens all throughout your body, you just don't know it and the only visible effects are in your throat. (to you)

Now as for why it's not a good idea to take too much antibiotics. Well you need your immune system to be perfectly functioning all the time, you can't keep taking antibiotics lest your bodies natural antibiotic system becomes less efficient. Or worse, it starts to reject the introduce antibiotics (allergies). These are both very bad situations for obvious reasons. However, when a doctor prescribes you antibiotics it is VERY important that you take the exact directions, including amount of time, given to you by the doctor. So if they tell you to take the antibiotics for 8 days but the infection appears to go away by day 4, do not stop taking them for fear of 'taking too much'.

Another reason to not take too much antibiotics, is because many antibiotics attack the system indescriminately. They will destroy good as well as bad bacteria. The good bacteria however is vital for your survival so... you don't want to destroy or harm these colonies .

Now as for antibiotic resistence, this happens for reasons stated in Tubba's post. However there are other reasons (which lead to the same conclusion but this is assuming the bacteria didn't originally have the 'resistence gene')
a)Mutation.
Bacteria are very simple organisms and as such are able to very rapidly mutate and evolve.
b)Horiztonal-gene transfer. Bacteria have the ability to 'give' DNA to other bacterial cells around it. So once that first bacteria is able to resist the antibiotics it would be able to give the required DNA to the other bacteria cells which in turn gives them the same resistence.
That's about all I have to add to this discussion.

EDIT: Something I forgot to add: While the mutation will allow for the bacteria to SURVIVE it came at quite a significant cost. The bacteria now struggles with its original function. So while it may survive in a hospital your immune system should naturally be able to defeat. Such struggles could be with functioning or with reproduction.

You can look at the 'anthrax scare' if you want to see this in action. The anthrax bacteria had developed EXTREME resistence to antibiotics that originally had worked to kill off the bacteria. It made this development in a pretty short amount of time. Now the misconception is that these bacteria are 'super-anthrax' this isn't true, they reproduce extremely slow. Slow enough that your natural immune system will defeat it without breaking a sweat.

Human immune system+reinforcements 1, Bad bacteria 0.

 

[TubbaBlubba]

b)Horiztonal-gene transfer. Bacteria have the ability to 'give' DNA to other bacterial cells around it. So once that first bacteria is able to resist the antibiotics it would be able to give the required DNA to the other bacteria cells which in turn gives them the same resistence.

Oh yes, prokaryotes are really cool in that way.

 

[Ygggdrasil]

I get antibiotics. So if these antibiotics enter bloodstream, how do they know they have to diffuse out right near the throat area. Are they diffusing all the time, going to unwanted places.

Antibiotics, and almost all drugs, don't know where they need to go. As you correctly surmise, they are diffusing everywhere in the body (except for places where most drugs are excluded, such as the brain). This fact is one of the reasons why drugs have side effects, and it is one of the reasons why chemotherapy is so difficult. Chemotherapy drug target rapidly dividing cells so as well as killing cancer cells, they also harm rapidly dividing cells in other areas of the body, such as in the bone marrow or in hair follicles.

Researchers are trying to develop methods to better target drugs to their sites of action in order to reduce off-target effects in other areas of the body. The classic idea is to simply find extracellular receptors (biomarkers) that are present only on cancer cells but not on other cells, and use these biomarkers to guide the drugs to their target. Unfortunately, it is very difficult to find useful biomarkers. There are, however, other strategies. For example, one could design drugs that are activated by light. Even though administration of the drug would spread it throughout the body, the drug would only have an effect on areas where doctors shine light of a specific wavelength (for example, on a tumor). Alternatively, one could use the cancer cell's own metabolism to activate the drugs. For example, metastatic cancer cells express certain proteases (enzymes that digest protein) which allow them to break their way through tissue and move into the bloodstream to colonize other areas of the body. Researchers have developed drugs that are initially inactive, but become active when acted up on by these proteases. It remains to be seen if this strategy really will help reduce the off-target effects of the drugs.

 

[sameeralord]

Thanks for all the answers . They were all very helpful Tubba and Zomg covered the questions I had. Ygggdrasil response I especially liked because it had many things I didn't know before.

 

[Andy Resnick]

Hello everyone,

Let's say I have a throat infection and all the bacteria are near the throat. I get antibiotics. So if these antibiotics enter bloodstream, how do they know they have to diffuse out right near the throat area. Are they diffusing all the time, going to unwanted places. Why is it bad to get antibiotics frequently, I can understand they will kill good bacteria, but how does this create antibiotic resistance to bad bacteria. Thanks

I'll just chime in with my experience using antibiotics in cell culture:

Generally, I have 3 types of antibiotics that I use: pen/strep, gentamicin, and fungizone (Amphotericin B). Penecillin/streptomyciin target gram-positive bacteria, gentamicin targets gram-negative, and fungizone goes after fungi. I use pen/strep and gentamicin constitutively, while fungizone gets used on an as-needed basis. I've also needed fluconozole for human cell culture.

I also have specialized antibiotics: kanamicin and G418 (geneticin).

All those antibiotics do different things: for example, pen/strep would kill my cells if used into high a concentration, while gentamicin simply cannot pass though the cell membrane. Similarly, fungi are more sensitive to fungizone than my cells, but if I use too much fungizone my cells would die as well.

When I transfect cells with, for example, a GFP fusion plasmid, the plasmid also contains a sequence that confers resistance to kanamicin (or geneticin). Thus, I can use kanamicin to select for transfected cells, as the wildtype cells get killed off.

Using pen/strep and gentamicin constitutively is not a good idea- I can help generate antibiotic-resistant strains of bacteria in the lab- but that's a trade-off many culture facilities consider when the environment is not as sterile as it should be. My lab and culture hood are in the Physics department, not the controlled environment of a medical research facility.

There is a very real problem of antibiotic-resistant bacteria in hospitals- partly due to the large amounts of antibiotics present, but also since the bacteria are near sick people. MRSA is one

http://en.wikipedia.org/wiki/Methicillin-resistant_Staphylococcus_aureus

as is tuberculosis:

http://en.wikipedia.org/wiki/Extensively_drug-resistant_tuberculosis

It's not clear how much all of the antibiotic-laden cleaning products used at home are contributing to the problem, but it's not zero.

Chemotherapy drugs are specific compounds that target surface molecules of rapidly growing cells: CD34, for example.

http://www.ebioscience.com/ebioscience/whatsnew/humancdchart.htm

However, 'normal' cells that also express these surface molecules (hair follicles, for example) are also killed off.

 

[bobze]

Well, I can answer your last question.

In a bacterial colony, there will always be a few bacteria with mutations that make them immune to the antibiotics (for instance, they might have slightly different protein receptors of some sort). If you kill the rest with antibiotics, only the immune bacteria will replicate, thus creating a new, mostly immune bacterial stem.

Just a quick semantics type of add;

Its not that some bacteria have mutations that make them 'immune', they are more resistant. Nothing is immune when you provide a significant dosage. I have MRSA's in the lab I could kill with oxicillin if I wanted (of course you have the weigh the in vitro consequences of dosage as well).

By shorting your round of antibiotics, you leave around more of those resistant ones than susceptible ones. The more resistant ones then, go on to reproduce and ah-la evolution.

Hello everyone,

Let's say I have a throat infection and all the bacteria are near the throat. I get antibiotics. So if these antibiotics enter bloodstream, how do they know they have to diffuse out right near the throat area. Are they diffusing all the time, going to unwanted places. Why is it bad to get antibiotics frequently, I can understand they will kill good bacteria, but how does this create antibiotic resistance to bad bacteria. Thanks

Your questions have been very well covered so I'll just add one bit here.

As you allude too, they can kill the good bacteria.

Most people don't realize, you have more bacterial cells in your body than you do Sameeralord cells (Who's body is it!).

Most of those bacteria are harmless, though many posses the ability to make trouble given the chance--Opportunistic is what you would call them.

So for example, you have bacteria that live in your gastrointestinal tract called clostridium difficile, which are fine living there and actually help you out some. However, if you were take a broad-spectrum (meaning low specificity--ie; it kills lots of types of bacteria) antibiotic like ciprofloxacin for extended amounts of time-You'd wipe out the other bacteria in your GI. Now, when your flora starts repopulating your GI the proportion of c. diff is too high and they 'take over'. Leaving you with one nasty case of diarrhea and colitis.

 

[bobze]

I'll just chime in with my experience using antibiotics in cell culture:

Generally, I have 3 types of antibiotics that I use: pen/strep, gentamicin, and fungizone (Amphotericin B). Penecillin/streptomyciin target gram-positive bacteria, gentamicin targets gram-negative, and fungizone goes after fungi. I use pen/strep and gentamicin constitutively, while fungizone gets used on an as-needed basis. I've also needed fluconozole for human cell culture.

I also have specialized antibiotics: kanamicin and G418 (geneticin).

All those antibiotics do different things: for example, pen/strep would kill my cells if used into high a concentration, while gentamicin simply cannot pass though the cell membrane. Similarly, fungi are more sensitive to fungizone than my cells, but if I use too much fungizone my cells would die as well.

When I transfect cells with, for example, a GFP fusion plasmid, the plasmid also contains a sequence that confers resistance to kanamicin (or geneticin). Thus, I can use kanamicin to select for transfected cells, as the wildtype cells get killed off.

Using pen/strep and gentamicin constitutively is not a good idea- I can help generate antibiotic-resistant strains of bacteria in the lab- but that's a trade-off many culture facilities consider when the environment is not as sterile as it should be. My lab and culture hood are in the Physics department, not the controlled environment of a medical research facility.

There is a very real problem of antibiotic-resistant bacteria in hospitals- partly due to the large amounts of antibiotics present, but also since the bacteria are near sick people. MRSA is one

http://en.wikipedia.org/wiki/Methicillin-resistant_Staphylococcus_aureus

as is tuberculosis:

http://en.wikipedia.org/wiki/Extensively_drug-resistant_tuberculosis

It's not clear how much all of the antibiotic-laden cleaning products used at home are contributing to the problem, but it's not zero.

Chemotherapy drugs are specific compounds that target surface molecules of rapidly growing cells: CD34, for example.

http://www.ebioscience.com/ebioscience/whatsnew/humancdchart.htm

However, 'normal' cells that also express these surface molecules (hair follicles, for example) are also killed off.

I think the effect is probably very small (referencing the boldface above). The problem has arisen in numerous ways.

First, patients don't follow orders and finish rounds of antibiotics.

Second, you have long term care facilities with patients on full time antibiotics. I see older people all the time, whose 'normal flora' is things like vancomycin resistant enterococci and methicillin resistant staphs. I've even had patients completely colonized by vanc resistant coagulase negative staphs!

Third, we have a very real problem of over-prescribing here in the states. Which comes from a combination poor lab work, lazy doctors and doctors trying to keep patients to pay the bills. You think your kid has strep throat? Well now you have to bring a doc's note that says they've been on antibiotics for 24 hours. Suppose those that labs are negative for strep A though, do you keep your kid home from school more time while the labs are ran again? You take off work too? Or do you pressure the doc into giving the meds? Doc won't do it? Go down the street, his competition would love to give your kid an unnecessary dose of penicillin-G so you can get him back to school and you back to work.

That's the kind of problem-scenarios that are wrecking our healthcare right now.

You don't have bugs resistant to fourth-generation cephalosporins, ESBL positive E. coli and KPCs because of cleaners, you have them because we've botched health care, public health and started up organism surveillance far too late in the game.

 

[Ygggdrasil]

While doctors over prescribing antibiotics is a concern, I don't think human use of antibiotics is the main problem here. For such drugs that have been touted as one of the most important developments in medical history, many people would be surprised that most antibiotics are not used to treat humans. Instead, 70% of all antibiotic use in the US is for farm animals (see: http://www.nytimes.com/2009/07/24/opinion/24fr3.htm , http://www.nytimes.com/2009/03/15/opinion/15kristof.html). Farm animals are regularly fed subtherapeutic doses of antibiotics in order to promote growth and lessen the chance of infections breaking out. One could not design a better practice in order to create new strains of antibiotic-resistant bacteria. Why are we squandering one of the most valuable tools in medical science in the name of cheap food? Apparently, we Americans care more about chicken McNuggets and Big Macs more than our health.

 

[Andy Resnick]

good point! I forgot about that.

 

[alxm]

While doctors over prescribing antibiotics is a concern, I don't think human use of antibiotics is the main problem here.

Well it's part of the problem. We don't have the same bacteria as animals; we're more worried about Mycobacterium tuberculosis than Mycobacterium bovis (bovine TB). The latter hasn't really been a concern since we started pasteurizing milk. Multiresistant TB is all due to us.

Of course, banning antibiotics as growth promotors in animal feed is still a very good idea, and the EU has already done so.

 

[Ygggdrasil]

Many of the bacteria that infect animals also infect us as well (e.g. E. coli, Salmonella, Staph. aureus, etc). Furthermore, as zomgwtf mentioned, a lot of horizontal gene transfer occurs between bacterial populations. Therefore, antibiotic resistances developed in farm animals can spread to bacteria that do not colonize farm animals like M. tuberculosis.

 

[bobze]

Well it's part of the problem. We don't have the same bacteria as animals; we're more worried about Mycobacterium tuberculosis than Mycobacterium bovis (bovine TB). The latter hasn't really been a concern since we started pasteurizing milk. Multiresistant TB is all due to us.

Of course, banning antibiotics as growth promotors in animal feed is still a very good idea, and the EU has already done so.

Farm animals was a good point I should have listed as a fourth reason.

Certainly our flora differs from animals', but many, many species are found in both humans and animals. Things like S. bovis and E. avium are being more common in clinical specimens and these organisms are certainly influenced by 'dosing animals'.

Also as Zomgwtf and Ygggdrasil mention prokaryote's ability to escape the woes of vertical gene transmission and readily exchange their genes with neighbors (often even of other species) has certainly played a role in some of the super-bugs we see clinically today--Especially in cases like some of Pseudomonads and Acinetobacter, which often move into replace 'normal flora' of long term care patients.

 

[ahmetbaba]

Well, antibiotics just destroy whatever they can. The reason why they can't kill regular human cells (as far as I know) is because human cells don't have the receptor sites that these antibiotics are looking for.

Antibiotics won't kill a single type of bacteria also, as I've said it will kill anything it attaches itself to, because of this, a common side effect of antibiotics is diarrhea. The antibiotics will just kill the regular beneficial bacteria in the digestive lining of a human, and you have diarrhea and all sorts of other problems.

 

[nismaratwork]

Well, antibiotics just destroy whatever they can. The reason why they can't kill regular human cells (as far as I know) is because human cells don't have the receptor sites that these antibiotics are looking for.

Antibiotics won't kill a single type of bacteria also, as I've said it will kill anything it attaches itself to, because of this, a common side effect of antibiotics is diarrhea. The antibiotics will just kill the regular beneficial bacteria in the digestive lining of a human, and you have diarrhea and all sorts of other problems.

Depends, it can disrupt the ability for critical signaling, or a stage in entering cells. How antibiotics work varies, and the toxicity to other cells is of course, an issue. Bleach is a great antibiotic, but it's unwise to take it intravenously because it will kill you along with the bugs.

Oh, on a sidenote, it is easy to just eat some yogurt or take a probiotic and spare yourself the misery of digestive issues.

 

[ahmetbaba]

well, bleach isn't an antibiotic. Bleach is something that has bactericidal properties due to its strong oxidizing compounds.

Antibiotics on the other hand are something else, obviously there are exceptions when antibiotics may kill human cells, but as I've said, antibiotics will kill anything they can attach their selves to, so if they can attach into a human cell, the human cell will die. But in most cases human cells have different receptor sites than bacteria where the antibiotics can differentiate between the two.

 

[nismaratwork]

well, bleach isn't an antibiotic. Bleach is something that has bactericidal properties due to its strong oxidizing compounds.

Antibiotics on the other hand are something else, obviously there are exceptions when antibiotics may kill human cells, but as I've said, antibiotics will kill anything they can attach their selves to, so if they can attach into a human cell, the human cell will die. But in most cases human cells have different receptor sites than bacteria where the antibiotics can differentiate between the two.

Bleach isn't used as an antibiotic in humans, but it is an antibiotic amongst other things. My point through an attempt at hyperbole was to say that antibiotics tend to target specific elements of bacterial invasion, signaling, or reproduction. In the case of bleach, it does this by destroying the cell outright through its superior oxidizing properties, but has the downside of not being targeted enough. Sulfur is the closest REAL compound, occasionally along with arsenic, that matches clinical use.

 

[darkfrog]

Sometimes the antibiotic is chosen based on the target organ. Different antibiotics will reach different levels in various parts of the body. For example, if I am treating osteomyelitis, I want an drug that can reach bone tissue well. If I am treating a cystitis, I want one that will reach high concentration in the urine. Sometimes, even an antibiotic that shows some resistance to particular bacteria on a sensitivity test will still be effective because it gets excreted by the kidneys so the concentration is much higher than the in vitro test indicates. There are other times when the best antibiotic based on lab tests is useless because it cannot reach the organ that is infected, for example may not be able to cross the blood-brain barrier to treat encephalitis.

 

[nismaratwork]

Sometimes the antibiotic is chosen based on the target organ. Different antibiotics will reach different levels in various parts of the body. For example, if I am treating osteomyelitis, I want an drug that can reach bone tissue well. If I am treating a cystitis, I want one that will reach high concentration in the urine. Sometimes, even an antibiotic that shows some resistance to particular bacteria on a sensitivity test will still be effective because it gets excreted by the kidneys so the concentration is much higher than the in vitro test indicates. There are other times when the best antibiotic based on lab tests is useless because it cannot reach the organ that is infected, for example may not be able to cross the blood-brain barrier to treat encephalitis.

Yep, but these days people tend to only think of the broad spectrum antibiotics, since they get the most press.