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How much Influence does selection has on antibiotic resistance?

The Influence of selection on antibiotic resistance is enormous influencing the rate of mutation. After a mutation that is potential to cause antibiotic resistance phenotype has occurred the bacteria with the mutated allele must compete with the wild -type ancestral bacterium. The degree of competitiveness and the result depends on the relative fitness of the mutant cell compared to the wild-type ancestral population. And therefore the ability to mutate and the selective process plays a major role in determining the rate of mutation. Antibiotic resistance changes bacterial fitness by decreasing or increasing. In the event it is decreased in fitness bacteria is normally cleared quicker before selection. However this decreased fitness can be compensated by other mutations in different loci of a chromosome resulting to equal or higher in fitness of the mutant allele compared to the wild-type ancestor. Furthermore, increased fitness in the antibiotic resistant bacteria brings about enormous mutation rates. Other factors that are important in the selective process are antibiotic concentrations and the physical structure of the selective habitat.

Inbreeding and antibiotic resistance

What effect would inbreeding have on antibiotic resistance?

Bacteria reproduce asexually and each of their offspring are clones of the parent. If one bacteria is antibiotic resistant and another is not, then the inbred or cloned offspring on the resistant bacteria will be the ones to survive in the presence of antibiotics. However, if the antibiotic is altered to attack the previously resistant bacteria then all clones of this bacteria will no longer be resistant and will die. As long as bacteria are constantly mutating there will almost always be an antibiotic resistant strain.

Question I
In calculating H^2 for antibiotic resistance we find that it is simply 1 as any trait aquired will be passed onto any offspring produced as sexual reproduction is typically not going to take place.

Bacterial Ribosomes and Antibiotic Resistance

1. It may be important to study antibiotic resistance by looking at protein folding and mis-folding because antibiotic resistance may come from the way proteins change how they fold or the proteins may begin to fold incorrectly from changes in either the virus or previous exposure to the antibiotic. If the way a protein folds changes then they may become resistant to an antibiotic due to that antibiotic no longer being able to attach to the ribosome like it previously had been able to.

2. The sequences of the prokaryotic NBD2 determinants may be similar to the eukaryotic ABCF family because the nucleotide binding domain (NBD) is common to all ABC proteins, and ABCF is a subfamily of ABC proteins, which means that the ABCF family contains NBD.

3. I think that the ribosome protection hypothesis best explains the mechanism of antibiotic resistance determinants. Antibiotic resistance determinants remove the driving force for antibiotic import by this method. If there is no driving force for import of the antibiotic then it cannot have access to the active site and is therefore resistant.

4. Bacteria face many selection pressures. When it comes to antibiotics those that are resistant are selected for and survive to pass on their resistance to their offspring. In the article they say that “such in vitro selection approaches allow for fine-tuning of the selective pressures in ways not permitted by the cellular environment and this for the isolation of mutants that might not emerge from an in vivo based selection.” When using in vitro selection the procedure is being done outside the living organism so many factors will be different than if the cell were still inside of the organism. Outside of the organism they can control any factor that they want, how they want. They can isolate antibiotic resistance ribosomes and treat them with various selective pressures, such as types of antibiotics, to see what works.

5. Any type of mutation can have detrimental effects, no matter how small. A transition is a mutation in which a purine is changed with a purine (A ↔ G) or a pyrimidine is changed with a pyrimidine (C ↔ T). A transversion is a mutation in which a purine is changed with a pyrimidine or a pyrimidine is changed with a purine (A or G ↔ C or T). A change is just one base pair can lead to the change of one of the amino acid within the sequence. A change in one amino acid can completely change a protein, and thus leading to a change in the ribosome. If the ribosome is different then there may be no active site for an antibiotic to attach to and it is therefore resistant.

6. I’m not sure but one possible reason why double-mutant ribosomes are more common than single-mutant ribosomes is that ribosomes with only one mutation may have no effect on the ribosome and therefore show no change. Ribosomes with double mutations are more likely to have a mutation that is going to show and will have an effect on the ribosome, and it is therefore noticed and thought to be more common.

Expert Interview on Antibiotic Resistance

In trying to understand more about antibiotic resistance and evolution we consulted Dr Bruce Hodges who practices Geriatric medicine and also an expert in Alzheimer's disease in Overland park, Kansas. Dr Hodges agreed to sit down with us for an interview on February, 27, 2009 at 9.00 am. The following is the transcript of the interview.

Question1. Dr Hodges tell us about yourself and why did you decide to pursue medicine?

After graduating college in Oklahoma I tried to find a job but my certificates were rejected that I had attended an institution that was not accredited. This was in the 50's soon after the end of world war II when the troops returned home, the GI bill was passed I decided to pursue medicine of which after graduating I went into teaching for a while and later Family practice. I then left family practice and began specializing in Geriatrics and Alzheimer's disease.

Question2. What are the common diseases that have shown resistance to antibiotics?

There are several, but Clostridium Difficile Colitis is most prevalent. It used to be one case a month but now it's one case every week. Also there is staphylococcus infections among them is Methicillin Resistant Staphylococcus Aureus (MRSA) that have shown resistance to Methicillin.

Question3. How do you attend to patients in the event that the infection has become resistant to available antibiotics?

We are running out of antibiotic choices because these bugs have developed resistances to the common organisms and vancomycin is one of our last resorts, rifampin is also another antibiotic that we are now combining with vancomycin for instance like Clostridium Difficile Colitis the treatment used to be flagyl and it worked very well but we have an organism now that has developed a resistance to flagyl so we added vancomycin. And now they are becoming resistant to vancomycin so we have to add rifampin.

Question4. Are there any guidelines governing the administration of antibiotics let's say from government agencies?

Well we have guidelines for antibiotics, the first thing is, in medicine try to do no harm, but on the same token our society has been taught to think that an antibiotic is a cure all and sometimes families or patients come to the doctor demanding an antibiotic when they really don't need one for instance, they will have a viral cold, an upper respiratory infection that's due to a virus but they want an antibiotic which is not going to affect the virus and if the doctor does not give them an antibiotic they will go to another doctor and get an antibiotic and the patients now are searching the internet to practice their own medicine and it makes it increasingly difficult because the family practioner in turn is trying to fulfill the needs of the patient at the Same time trying to practice good medicine. And sometimes the families do not want to hear that, what they are asking for is not good medicine, we see it not only with antibiotics, but with other medicine, you know we are in an Alzheimer's facility here and the families will research almost every drug that we recommend and they will see a possible side effect and think it will cause a side effect, it's possible but it doesn't necessarily mean every person is going to develop it as a result, that's a big part of medicine, is trying to convince the patient ... let me try this..Let me do this, this is why? But its constant education process.

Question5. So do you think it's important for doctors to know about evolution?

Oh yes, because we know that when you talk about evolution of resistance, that comes about by mutations and genetic changes and so forth and we do know that organisms mutate and change within a species, we do not have direct evidence that organisms progress from one species to another, I think people who believe in evolution have thought that's what happens and we do seem to have an evolutionary chain, a progression of organisms but we have yet to have proof of one organisms actually evolving into a different species, but we know that within a species organisms change. So do you believe in evolution? I believe in evolution in the fact that obviously things change, theirs physical evolution and biological evolution I don't have the final answer.

Question6. Did you celebrate Darwin's day?

No I recognized it in my mind um... theirs a poem I wish I could remember it all, it goes something like three monkeys were sitting in a coconut tree discussing things as they said to me said one to the other, now listen you two the idea that man descended is a big taboo and they went on to say that no monkey ever put a fence around his coconut tree permitting all others to enjoy the coconut and no monkey ever beat his wife or took a knife and took another's life. And it goes on like that and at the end it says man may have descended the ornery curse but he sure didn't descend from us. ....it's kind of a clever poem.

Question7. So in a group of let's say four patients that you have attended how many do you think are knowledgeable about the use of antibiotics?

You mean in my patients? YES ...out of four patients? YES .....most of them think that an antibiotic is a miracle, it's going to cure every problem they seem to think that one antibiotic can cure every disease which we know is not true and the knowledge that the general public hears is that if you get sick and you take the antibiotic and don't get well because you had a virus and they think the doctor didn't know what he was doing

Question8. So is that the common misconception that people have concerning antibiotics?

A lot of misconceptions of antibiotics exist and it's very difficult to convince people you don't need an antibiotic in this situation and we grow....let's take this Alzheimer's facility 80 - 90 % of these little ladies if we culture their urine they would have a positive urine culture but they are not infected, they are colonized and they are asymptomatic, they do not need an antibiotic. First of all the antibiotic won't clear the urinary tract infection or if it does they will be recolonized within a few weeks because they are most likely incontinent the urethral opening is weak so if an organism migrates up into the bladder it will colonize and infect.