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Old 27th April 2011, 02:16 AM   #1
Kumar
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Lightbulb Antibiotic Resistance & Useful Bacterias?

Hello,

I have few simple questions about antibiotic resistance(popped up from discussions in Topic "antibiotic coming to end":-

1. How excessive useful bacterias in intestines( normally or on taking of pre/pro-biotic) can present side effects?

2. Since we ingest useful bacterias daily with food, yogurt etc., and these can also be killed by antibiotics and so can also become resistant to antibiotics. Not taking full course of antibiotics can make bacterias resistant to antibiotics. Say, an antibiotic course is of 5 days for some GI tract infection. So when we will ingest useful bacterias (say in yogurt) on 4th to 6th day after start of antibiotic course, will such bacterias ingested on 4th to 6th day will not become resistant because not undergone full antibiotic course of 5 days? Since immune system don't act on useful bacterias, we can't say that those later entrants can be handled by immune system. Probably, people who had previously taken antibiotics, should also be chronically suffering from GI problems/distention, somewhat over filling sensation, obstructions, lack of motility, mucus formation, unclear motions, excessive but non smelling gas etc.(as if from excess of useful bacterias).

Probably, such condition should also prevailing in other body systems which are directly exposed to outside environment--Respiratory & Urinary tracts.

Probably, this issue may also be relevant to other pathogens.

So please teach me accordingly.

Best regards.
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Old 27th April 2011, 02:18 AM   #2
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Wrong forum.
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Old 27th April 2011, 02:20 AM   #3
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Originally Posted by Pixel42 View Post
Wrong forum.
Sorry. It is due to oversight. I already requested modretor to move it to Science forum.
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Old 27th April 2011, 02:35 AM   #4
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Old 27th April 2011, 03:07 AM   #5
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Originally Posted by Kumar View Post
Hello,

I have few simple questions about antibiotic resistance(popped up from discussions in Topic "antibiotic coming to end":-

1. How excessive useful bacterias in intestines( normally or on taking of pre/pro-biotic) can present side effects?

2. Since we ingest useful bacterias daily with food, yogurt etc., and these can also be killed by antibiotics and so can also become resistant to antibiotics. Not taking full course of antibiotics can make bacterias resistant to antibiotics. Say, an antibiotic course is of 5 days for some GI tract infection. So when we will ingest useful bacterias (say in yogurt) on 4th to 6th day after start of antibiotic course, will such bacterias ingested on 4th to 6th day will not become resistant because not undergone full antibiotic course of 5 days? Since immune system don't act on useful bacterias, we can't say that those later entrants can be handled by immune system. Probably, people who had previously taken antibiotics, should also be chronically suffering from GI problems/distention, somewhat over filling sensation, obstructions, lack of motility, mucus formation, unclear motions, excessive but non smelling gas etc.(as if from excess of useful bacterias).

Probably, such condition should also prevailing in other body systems which are directly exposed to outside environment--Respiratory & Urinary tracts.

Probably, this issue may also be relevant to other pathogens.

So please teach me accordingly.

Best regards.
OK; a reasonable question, so you get a reasonable answer.

The intestinal flora may evolve resistance to antibiotics under such conditions as you mention, but since it is not harmful, that does not matter much.

Once the antibiotics are out of your system, the resistant germs have no advantage over other germs. In fact, since resistance may come at some cost, they may be at a disadvantage. At any rate, since the lifetime of each germ is short (days), they will soon die out again.

Thus, there is no reason to expect long-term effects from this.

Hans
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Old 27th April 2011, 06:35 AM   #6
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Originally Posted by MRC_Hans View Post
OK; a reasonable question, so you get a reasonable answer.

The intestinal flora may evolve resistance to antibiotics under such conditions as you mention, but since it is not harmful, that does not matter much.

Once the antibiotics are out of your system, the resistant germs have no advantage over other germs. In fact, since resistance may come at some cost, they may be at a disadvantage. At any rate, since the lifetime of each germ is short (days), they will soon die out again.

Thus, there is no reason to expect long-term effects from this.

Hans
Thanks & welcome.

Next generations of resistant bacterias should also be resistant. So question of short life span may not be relevant in this sense. If survival rate is higher & they can't be killed by antibiotics to control, probably their excessive presence should be possible in intestines. Can't say if we can get GI tract probeems & even to infection level due to excessive presence of beneficial bacterias. Probiotics also have side effects. I am not sure if resistnt variety of bacterias are having longevity & higher survival rate than normal bactrias.
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Old 27th April 2011, 06:47 AM   #7
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Originally Posted by Kumar View Post
Thanks & welcome.

Next generations of resistant bacterias should also be resistant. So question of short life span may not be relevant in this sense. If survival rate is higher & they can't be killed by antibiotics to control, probably their excessive presence should be possible in intestines.

Did you bother to read what Hans posted? Here's the relevant bit:
Originally Posted by MRC_Hans
Once the antibiotics are out of your system, the resistant germs have no advantage over other germs. In fact, since resistance may come at some cost, they may be at a disadvantage. At any rate, since the lifetime of each germ is short (days), they will soon die out again.

Antibiotic resistance is only an advantage in the presence of the antibiotic. It represents a cost to the bacteria because they have to expend energy on it. In the absence of the antibiotic, resistant bacteria are therefore at a disadvantage. They will be outcompeted and replaced by the non-resistant bacteria that are (as you say) ingested daily, and so will die out.

Of course, since this doesn't fit your quackery-promoting agenda, you will just ignore it.
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Old 27th April 2011, 07:06 AM   #8
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Originally Posted by Mojo View Post
Did you bother to read what Hans posted? Here's the relevant bit:


Antibiotic resistance is only an advantage in the presence of the antibiotic. It represents a cost to the bacteria because they have to expend energy on it. In the absence of the antibiotic, resistant bacteria are therefore at a disadvantage. They will be outcompeted and replaced by the non-resistant bacteria that are (as you say) ingested daily, and so will die out.

Of course, since this doesn't fit your quackery-promoting agenda, you will just ignore it.
Avoid odds because we are understanding to each other here. Will resistent bacterias not replicate & multiply into resitant daughter bacterias?
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Old 27th April 2011, 08:37 AM   #9
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Kumar -

Please read what people tell you. If you don't agree, argue against it, but don't just blow them off.

Originally Posted by MRC_Hans View Post
Once the antibiotics are out of your system, the resistant germs have no advantage over other germs. In fact, since resistance may come at some cost, they may be at a disadvantage. At any rate, since the lifetime of each germ is short (days), they will soon die out again.

Thus, there is no reason to expect long-term effects from this.
Originally Posted by Mojo View Post
Antibiotic resistance is only an advantage in the presence of the antibiotic. It represents a cost to the bacteria because they have to expend energy on it. In the absence of the antibiotic, resistant bacteria are therefore at a disadvantage. They will be outcompeted and replaced by the non-resistant bacteria that are (as you say) ingested daily, and so will die out.

So what part of those statements didn't you understand?

Originally Posted by Kumar View Post
Next generations of resistant bacterias should also be resistant. So question of short life span may not be relevant in this sense. If survival rate is higher & they can't be killed by antibiotics to control, probably their excessive presence should be possible in intestines.

There is no reason to believe "survival rate is higher". Yes, resistant bacteria will try to replicate after the antibiotic is gone. However, they will have to compete with non-resistant bacteria. With the antibiotic gone, resistance is no longer an advantage, and probably a disadvantage. So the resistant bacteria will die out.
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Old 27th April 2011, 09:12 AM   #10
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Why the assumption genes for antibiotic resistance come at a cost?
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Old 27th April 2011, 10:19 AM   #11
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Originally Posted by Ivor the Engineer View Post
Why the assumption genes for antibiotic resistance come at a cost?
Not assumption. Observation. The things bacteria can do to resist antibiotics either take energy that the bacterium could use for something else, or change how they interact with the external world. And since evolution has tuned their interactions already, the result is reduced fitness relative to non-resistant bugs when there is no antibiotic presence.

And it's not always true. But generally, yes.
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Old 27th April 2011, 11:37 AM   #12
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Originally Posted by WhatRoughBeast View Post
Not assumption. Observation. The things bacteria can do to resist antibiotics either take energy that the bacterium could use for something else, or change how they interact with the external world. And since evolution has tuned their interactions already, the result is reduced fitness relative to non-resistant bugs when there is no antibiotic presence.

And it's not always true. But generally, yes.
I think you were correct to say 'could' come at a cost. But not necessarily 'would' come at a cost. A lot of genetic code goes into dormancy when not needed by bacteria but quickly reemerges when re-exposed to the toxic antibiotic.

For example, an organism develops resistance. The antibiotic is withdrawn and non-resistant organism predominate again. But when you reintroduce the antibiotic, drug resistance re-emerges much more quickly suggesting the genetic code merely quit operating but remained in the wings.
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Old 27th April 2011, 12:04 PM   #13
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Originally Posted by Skeptic Ginger View Post
I think you were correct to say 'could' come at a cost. But not necessarily 'would' come at a cost. A lot of genetic code goes into dormancy when not needed by bacteria but quickly reemerges when re-exposed to the toxic antibiotic.

For example, an organism develops resistance. The antibiotic is withdrawn and non-resistant organism predominate again. But when you reintroduce the antibiotic, drug resistance re-emerges much more quickly suggesting the genetic code merely quit operating but remained in the wings.
I think would come at a cost for two reasons.
First because the wild type organism is pretty streamlined, and most mutations will lead to some cost.
Second, because a great many resistance genes are carried separately from the main chromosome, on a plasmid and making a plasmid would have an evident cost. Those plasmids are often some variety of male and the mutation just consists of the transfer of the resistance plasmid to the non-resistant strain. Since the plasmid may carry a great variety of resistance genes - one ends up with an increasing prevalence of multidrug resistant organisms.

As an aside, there are a variety of male specific phage (bacterial viruses) which only infect male or plasmid carrying strains. It has always seemed to me that one could use such viruses as adjuncts to antibiotic treatment but I have never heard of such treatments being implemented. I am sure there is some good reason why not.
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Old 27th April 2011, 02:37 PM   #14
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Furthermore, even if resistance initially comes at a fitness cost, compensatory mutations can emerge over time that will bring the fitness of the resistant strain back in line with that of the wild type
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Old 27th April 2011, 07:56 PM   #15
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Originally Posted by WhatRoughBeast View Post
Kumar -

Please read what people tell you. If you don't agree, argue against it, but don't just blow them off.






So what part of those statements didn't you understand?




There is no reason to believe "survival rate is higher". Yes, resistant bacteria will try to replicate after the antibiotic is gone. However, they will have to compete with non-resistant bacteria. With the antibiotic gone, resistance is no longer an advantage, and probably a disadvantage. So the resistant bacteria will die out.
I feel you are right, in sense that resistant bacterias will be similar to normal bacterias in all sense but will not be killed by same antibiotics. Probably this can also be advantageous to host carring resistant bacterias because those bactrias will not be killed by next dose of same/similar antibiotics.

Does it suggest that it is advantageous to host to get resistant beneficial bacterias?
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Old 28th April 2011, 01:06 AM   #16
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Originally Posted by Kumar View Post
I feel you are right, in sense that resistant bacterias will be similar to normal bacterias in all sense but will not be killed by same antibiotics. Probably this can also be advantageous to host carring resistant bacterias because those bactrias will not be killed by next dose of same/similar antibiotics.
As already mentioned, they will not stay resistant for more than a few generations (of bacteria). The intestinal flora is constantly replenished and changes according to the kind of food you eat.

There is a hypothetical possibility that antibiotic resistance can come without cost to the bacteria, but this is unlikely. To resist antibiotics requires some kind of extra function, probably some proteine, and it will nearly always come at a cost.

Quote:
Does it suggest that it is advantageous to host to get resistant beneficial bacterias?
Well, if that host is to be subjected to frequent antibiotic treatments, then maybe. For most people, no.

Hans
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Old 28th April 2011, 01:08 AM   #17
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Originally Posted by Tracy Dalziel View Post
Furthermore, even if resistance initially comes at a fitness cost, compensatory mutations can emerge over time that will bring the fitness of the resistant strain back in line with that of the wild type
That is possible, but if there is no selection pressure (no more antibiotics present) there is little reason to expect it to happen.

Hans
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Old 28th April 2011, 01:24 AM   #18
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Originally Posted by John Hewitt View Post
As an aside, there are a variety of male specific phage (bacterial viruses) which only infect male or plasmid carrying strains. It has always seemed to me that one could use such viruses as adjuncts to antibiotic treatment but I have never heard of such treatments being implemented. I am sure there is some good reason why not.
I don't know if such a general approach to the targeting of bacteria is possible, but certainly more specific tailored viruses could work. Viral treatments for cancer are in trials now, and quite promising. That could open the door to viral treatments for other things.
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Old 28th April 2011, 01:26 AM   #19
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Originally Posted by MRC_Hans View Post
As already mentioned, they will not stay resistant for more than a few generations (of bacteria). The intestinal flora is constantly replenished and changes according to the kind of food you eat.

There is a hypothetical possibility that antibiotic resistance can come without cost to the bacteria, but this is unlikely. To resist antibiotics requires some kind of extra function, probably some proteine, and it will nearly always come at a cost.



Well, if that host is to be subjected to frequent antibiotic treatments, then maybe. For most people, no.

Hans
Thanks. It is quite clear to me.
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Old 28th April 2011, 12:44 PM   #20
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Originally Posted by John Hewitt View Post
I think would come at a cost for two reasons.
First because the wild type organism is pretty streamlined, and most mutations will lead to some cost.
Second, because a great many resistance genes are carried separately from the main chromosome, on a plasmid and making a plasmid would have an evident cost. Those plasmids are often some variety of male and the mutation just consists of the transfer of the resistance plasmid to the non-resistant strain. Since the plasmid may carry a great variety of resistance genes - one ends up with an increasing prevalence of multidrug resistant organisms.
...
Still just an assumption on your part. I am curious if you could find even one example in the literature where extra genetic material that is not activated costs a microorganism anything.
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Old 28th April 2011, 12:49 PM   #21
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Originally Posted by Tracy Dalziel View Post
Furthermore, even if resistance initially comes at a fitness cost, compensatory mutations can emerge over time that will bring the fitness of the resistant strain back in line with that of the wild type
The USA 300 strain of MRSA is an example not of a "fitness cost" of drug resistance but rather the opposite, it has become a worldwide pandemic strain probably because of a synergistic benefit rather than a cost.

The assumption that any and all drug resistance comes at a cost is not supported by the evidence. The cost could easily be so minor as to be insignificant.

The assumption of a fitness cost to antibiotic resistance is analogous to Occam's Razor, it's a principle, not an absolute like a law in physics.
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Old 29th April 2011, 02:58 AM   #22
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Originally Posted by Skeptic Ginger View Post
The assumption of a fitness cost to antibiotic resistance is analogous to Occam's Razor, it's a principle, not an absolute like a law in physics.
That is, of course, true.

In all this we have assumed that intestinal bacteria are cabable at all to develope antibiotic resistance. I don't know if some of them can, but certainly not all bacteria have this ability.

Hans
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Old 29th April 2011, 09:47 AM   #23
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Originally Posted by MRC_Hans View Post
That is, of course, true.

In all this we have assumed that intestinal bacteria are cabable at all to develope antibiotic resistance. I don't know if some of them can, but certainly not all bacteria have this ability.

Hans
The gut flora includes many organisms capable of developing drug resistance.
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Old 29th April 2011, 01:17 PM   #24
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Originally Posted by Skeptic Ginger View Post
The USA 300 strain of MRSA is an example not of a "fitness cost" of drug resistance but rather the opposite, it has become a worldwide pandemic strain probably because of a synergistic benefit rather than a cost.

The assumption that any and all drug resistance comes at a cost is not supported by the evidence. The cost could easily be so minor as to be insignificant.

The assumption of a fitness cost to antibiotic resistance is analogous to Occam's Razor, it's a principle, not an absolute like a law in physics.
Yes, that was the point I was making.
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Old 30th April 2011, 12:19 PM   #25
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Originally Posted by Skeptic Ginger View Post
The gut flora includes many organisms capable of developing drug resistance.
I accept that.

Hans
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Old 30th April 2011, 03:59 PM   #26
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http://www.nejm.org/doi/full/10.1056/NEJMp1011715

Quote:
...

The story of the beta-lactamases is a case in point. The first enzyme capable of destroying penicillin was described before the initial clinical application of penicillin in the early 1940s. The discovery of compounds resistant to beta-lactamases (e.g, cephalosporins and carbapenems) or capable of inactivating them (e.g., beta-lactamase inhibitors) has simply been met with the evolution of new beta-lactamases, often through mutations that inactivate these antibiotics. At present, more than 890 such unique enzymes have been discovered — far more than the antibiotics developed to combat them.3

Some of these enzymes are chromosomally mediated, but the majority of them are found on transmissible genetic elements, and for the most part, acquisition of the resistance genes does not result in a huge fitness cost to the recipient organism. This is not true of all types of resistance, however. Resistance to oxazolidinones, such as linezolid in the case of S. aureus, is an example of a resistance mechanism that does extract a fitness cost. Because the oxazolidinone target on the 23S ribosomal RNA of the ribosome exists in multiple (four to six) copies, it requires several mutations for organisms to develop resistance, and these mutations are clearly associated with a decrease in fitness. This may account for the fact that for the first decade or so of linezolid use, the emergence of resistance in S. aureus has been relatively uncommon.

However, nature clearly abhors a vacuum, and recently a new mechanism of resistance has been discovered, initially in staphylococci in swine in Germany.

...
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