SCI-ART LAB

Science, Art, Litt, Science based Art & Science Communication

Why antibiotic resistance is increasing and how our friendly ubiquitous scientists are trying to tackle it

Why is antibiotic resistance increasing? It is the result of evolution!

And why should bacteria evolve? In order to survive! Because antibiotics are their 'poison'.

If they can't surmount this problem of antibiotic use by us to suppress or kill them they cannot live and propagate. It will be the end of the story for them on this planet. So they got smarter and are trying to beat us in the game.

Ever since the scientists started to control these little creatures by discovering and sometimes 'making' synthetic antibiotics, the battle between the two got more intense. And ignorance and selfishness of a few people are making things easier for the microbes and difficult for the scientists!

Surprised to hear this? Yes, some people are helping our enemy, the bacteria, and not the friendly scientists who are toiling day and night to protect them from deadly diseases!

My complaint has solid reasons and let me tell you now how this has been happening.

Alexander Fleming discovered the first antibiotic, penicillin, in 1927. The world started using antibiotics in the 1940s, and this transformed medical care and dramatically reduced illness and death from infectious diseases. Millions have been saved from certain departure from life. The word "antibiotic" originally referred to a natural compound produced by a fungus or another microorganism that kills bacteria (that is why anti- biotic, which roughly means,  ‘doubting the possibility of life in a particular environment') which cause disease in humans or animals. Some antibiotics may be synthetic compounds (not produced by microorganisms) that can also kill or inhibit the growth of microbes. Although antibiotics have many beneficial effects, their use itself has contributed to the problem of antibiotic resistance.

The ability of bacteria or other microbes to resist the effects of an antibiotic is called antibiotic resistance. It occurs when bacteria change in some way that reduces or eliminates the effectiveness of drugs, chemicals, or other agents designed to cure or prevent infections. The bacteria survive and continue to multiply causing more harm. Almost every type of bacteria has become stronger and less responsive to antibiotic treatment now when it is really needed. The easily treatable infections are now becoming deadly diseases like in the pre-antibiotic era.

Each time we use an antibiotic, the weak microbes get killed or controlled. But the stronger and resistant ones survive and propagate their line of resistant organisms. Bacteria can do this through several mechanisms. Some bacteria develop the ability to neutralize the antibiotic before it can do harm, others can rapidly pump the antibiotic out, and still others can change the antibiotic attack site so it cannot affect the function of the bacteria.

Exposure to antibiotics therefore provides selective pressure, which makes the surviving bacteria more likely to be resistant. Moreover, bacteria that were at one time susceptible to an antibiotic can acquire resistance through mutation of their genetic material or by acquiring pieces of DNA that code for the resistance properties from other bacteria. The DNA that codes for resistance can be grouped in a single easily transferable package. This means that bacteria can become resistant to many antimicrobial agents because of the transfer of one piece of DNA. Gene transfer from resistant bacteria to the non-resistant one causes the latter to become resistant and survive.

These resistant bacteria are called "super bugs" because of their acquired characters.

Inappropriate Use of antibiotics is the main reason for drug resistance

Selection of resistant microorganisms in Nature is enhanced by inappropriate use of antimicrobials.

Sometimes healthcare providers will prescribe antimicrobials inappropriately, wishing to please an insistent patient who has a viral infection or an as-yet undiagnosed condition. And some take it as a precautionary measure even if they don't have a bacterial infection just because others around have it!

Very often, healthcare providers must use incomplete or imperfect information to diagnose an infection and thus prescribe an antimicrobial just-in-case or prescribe a broad-spectrum antimicrobial when a specific antibiotic might be better. These situations contribute to selective pressure and accelerate antimicrobial resistance.

Critically ill patients are more susceptible to infections and, thus, often require the aid of antimicrobials. However, the heavier use of antimicrobials in these patients can worsen the problem by selecting for antimicrobial-resistant microorganisms. The extensive use of antimicrobials and close contact among sick patients create a positive environment for the spread of antimicrobial-resistant germs.

Then some who don't have adequate money stop using the costly antibiotics ( because they cannot afford the full treatment) as soon as they start feeling a little better. Some take low cost low dosage and even spurious medicines. The microbes that cause their infections either mutate as they get inferior toxin or get respite from the deadly toxins they are fighting against and develop resistance to them.

You think antibiotics belong to hospitals and homes. But greed and unawareness are taking them to the fields! Some farmers are spraying the anitbiotics in the fields to increase their farm yields making most of the soil bacteria resistant, while others are using them to feed animals like chicken as growth enhancers to make them fatter! Do you know in some countries, more than half of the antibiotics produced are being used for agricultural purposes than for treating deadly diseases? Agribusinesses, sadly, defend the practice as necessary to help keep cattle, pigs and chickens healthy and to increase production of meat. Dangerous overuse of antibiotics by the agricultural industry has been on the rise at an alarming rate in recent years, putting the effectiveness of our life-saving drugs in jeopardy for people when they get sick.

Low concentrations of antibiotics that are getting into sewerage (2) and other water systems through excretion of body fluids by patients (one doctor told me a patient of his spits as soon as the tablet is taken into her mouth because it tastes bitter and despite asking her to put it directly into the throat and not the mouth and not to spit by the doctor she continues to do it!) and washing of things used for antibiotic administration like syringes and hands by health care staff and sometimes through the route of waste product disposal by the pharmaceutical industries are also contributing to the problem.

Consequences of drug resistance by microbes...

Do you know in South Africa, patients with tuberculosis that has developed resistance to all known antibiotics are already simply sent home to die? That is how pathetic the situation has become in some parts of the world.

Many of the available treatment options for common bacterial infections are becoming more and more ineffective. The infections are becoming longer and deadly. As a consequence, there are situations where infected patients cannot be treated adequately by any of the available antibiotics. This resistance may delay and hinder treatment, resulting in complications or even final exit from this world. Moreover, a patient may need more care, as well as the use of alternative and more expensive antibiotics, which may have more severe side effects, or may need more invasive treatments. When infection stays longer, other people around will have more chance of developing it. We are now entering a very dangerous post-antibiotic era! Starting to get worried?

But...wait...we have our  friendly ubiquitous, but invisible, scientists to help us solve this problem. And they are doing their best to control and reduce the mess the world is in right now.

 

How scientists are fighting now to tackle this problem

A. Educating people and governments and bringing awareness. They are asking them to....

*use available antibiotics judiciously and, when possible, help in infection prevention through appropriate vaccination.
*take hygienic precautions for the control of cross-transmission of resistant strains between persons, including screening for resistant strains and isolation of carrier patients.
*stop using antibiotics unnecessarily  in farms and other places, they should not be using at.
*treat sewerage and industrial antibiotic pollutants before releasing them into our surroundings.


B. Development of antibiotics with new mechanism of action. Scientists now are after new and better antibiotics, or trying new approaches to kill bacteria without killing the host.

Trying new drug cocktails is one method. A combination of drugs,instead of one, can yield more positive results. Then directly giving those drugs through injections and inhalation, allowing higher concentrations to reach the target areas and killing the resistant organisms instantly before they pass on the resistance to other bacteria.

Scientists are embracing biomimicry too. With the understanding that more than half of all medicines used today are either derived from or inspired by bacteria, plants, or animals, it’s a matter of looking in the right places. Searching Nature for the products is the most important one. They are packing chemicals, microscopes, test tubes, and other lab equipment in their suitcases and travelling around the world in search of answers in the unlikeliest of places, including the guts of insects and the mud and sediment from deep sea trenches! Some are literally searching for drugs in the dirt. Others are going deep into ocean and sea bottoms proving to the world that there is no unconquerable place on our planet for the scientific community when they are determined to save the living beings.

Scientists have announced two years back their discovery of a potential substance that can turn off antibiotic resistance. They have isolated the substance from a soil fungus in eastern Canada. The fungus makes a chemical that disarms a gene in certain drug-resistant bacteria. That gene had allowed the bacteria to survive certain antibiotics. The researchers described their achievement in June 25 2014 issue of the journal Nature. Such findings suggest that in some cases, resistance to antibiotics can be switched off. Can we make use of this information? Yes, scientific community has already started doing this! 

Blocking the formation of biofilms can enhance bacterial susceptibility to antibiotics and prevent the development of resistance, according to some studies (6) which say antibiotics can continue to be effective if bacteria’s cell-to-cell communication and ability to latch on to each other are disrupted.

The study concentrated on the mechanisms of how bacteria are able to tolerate antibiotics by using a common bacterium, Pseudomonas aeruginosa. The researchers allowed bacteria to form a wall of biofilm in a microfluidic system, at which point they introduced an antibiotic. A large portion of the bacterial cells were killed by the antibiotic, leaving only a small fraction of antibiotic-tolerant cells. However, these cells were able to reproduce rapidly and dominate the community. The scientists then used an FDA-approved drug that disrupts cell-to-cell communication—known as quorum sensing—and velcro-like cells that can move and “stick” to each other. Together, they managed to kill all the bacterial cells. The same tests were then performed on mice with infected implants. It was found that only mice treated with a combination of an anti-biofilm compound and antibiotics had their infections completely eradicated. 

Resorting to smart techniques is the method followed by some. Modern gene-sequencing machines mean it is now possible to read microbial DNA quickly and cheaply, opening up a new era of "genome mining which has reignited interest in seeking drug leads in the natural world. Some bacteria, viruses, fungi and other organisms use compounds that fight their enemies and competitors. Scientists are searching for these compounds very vigourously.

A promising molecular target that is unlikely to develop antibiotic resistance has been identified in bacteria recently (1). Now scientists are trying to target this and similar molecular sites to develop new methodology to win the game.

Working at molecular levels, some scientists are identifying weaknesses in bacterial defense mechanisms and are trying to to attack these sites (4, 5).

Several microbiologists are engineering harmless pro-biotic bacteria to sense and destroy disease-causing gut bacteria.

Bacteriophages are viruses that infect bacteria, and in the great war between humans and pathogenic bacteria they can act as allies for both sides. Phages that destroy their host bacteria can be used as antimicrobial therapy, complementing or replacing antibiotics. But as phages are essentially little capsules that carry DNA from one bacteria to another, they can also spread the genes that make bacteria resistant to antibiotics. Scientists are now creating phages that can help antibiotics work against even resistant bacteria.These viruses make proteins that derail the bacteria’s DNA-repair system. The novel phages can boost by 100 to 10,000 times how well an antibiotic works (3).

Recently scientists have found that Combination Of Three Drugs Increases Effectiveness

Combinations of three different antibiotics can overcome bacteria's resistance to antibiotics, even when none of the three drugs on their own - or even two of the three together - is effective, scientists have found.

They grew E coli bacteria in a laboratory and treated the samples with combinations of one, two and three antibiotics from a group of 14 drugs.The biologists studied how effectively every single possible combination of drugs worked to kill the bacteria. Some combinations killed 100% of the bacteria, including 94 of the 364 three-drug groupings tested.

According to Pamela Yeh from the University of California, Los Angeles (UCLA), the success rate might have been even greater if the researchers tested higher doses of the drugs. Elif Tekin, UCLA graduate student, helped create a sophisticated framework that enabled the scientists to determine when adding a third antibiotic was producing new effects that combinations of just two drugs could not achieve.“Three antibiotics can change the dynamic. Not many scientists realise that three-drug combinations can have really beneficial effects that they would not have predicted even by studying all pairs of the antibiotics together,“ she said.

Different classes of antibiotics use different mechanisms to fight bacteria. One class, which includes amoxicillin, kill bacteria by preventing them from making cell walls. Another disrupts their tightly coiled DNA. A third inhibits their ability to make proteins. But there had been little previous research indicating that combinations of three antibiotics might be more potent together than any two of them. “People tend to think that you don't need to understand interactions beyond pairs. We found that is not always so,“ said Van Savage, a UCLA associate professor.

The researchers combined techniques from biology and mathematics to determine which groups of antibiotics would be most effective.

Yes, scientists are leaving no stone un-turned in this fight against our enemies.

But the scientific community is worried because when new antibiotics are identified they too might get misused and become ineffective in a matter of short time with a careless attitude. Therefore, they are asking people to co-operate and help them keep antibiotics and other mechanisms that kill our enemies safe and away from becoming the targets of resistance. Can the world do this? It must and should. Because the very survival of mankind hinges upon this combined effort.

Help the scientists help you, friends!

How you and your Governments can help...

1. Improve sanitation. Fewer infections mean fewer antibiotics.

2. Stop taking antibiotics for infections that don't need them  like viral diseases/infections.           Hospitals should develop better, faster, cheaper diagnostic tools, so doctors don’t have to assess vague symptoms, or rely on slow, expensive tests based on centuries-old technology. 

3. Use vaccines to prevent diseases in the first place.   

4. Start surveillance  to monitor the use of antibiotics and the spread of resistant microbes.

5. Set targets to reduce the use of antibiotics    

6. Bring awareness among people, educate them about uses and misuses.

7. Stop antibiotic use in agriculture.

8. Use better surveillance methods on pharma industries.

9. Stick to prescription. Don't stop taking antibiotics until your doctor asks you to.

                                                   

Dr. Krishna Kumari Challa's poem based on this theme...( from the group art-literature-science interplay )

http://kkartlab.in/group/theartofwritingpoems/forum/topics/the-wond...

The wonderful magic called antibiotic

Antibiotic, antibiotic, antibiotic

It can make life miserable for the 'harmful' biotic

A boon to treat infections chronic

But losing all its magic

Because of thoughts and actions miopic

Humankinds' misery is reaching heights astronomic

Making the resistance  more frequent and the bacteria frolic!

Now how can we control these creatures microscopic?

By making resistant-proof drugs from Nature's pharmacologic

Taking the help of molecular epidemiologic

Engineering viruses bacteriophagic

Going to the depths of aquatic

Searching all stuff  'dustic'

Using  things rustic

Scientists are making signs triumphatic

Soon they will be singing victory music!

References:

1. http://elifesciences.org/content/3/e02840v1

2. http://blogs.scientificamerican.com/food-matters/resistance-from-th...

3. http://www.bu.edu/abl/files/pnas_lu2.pdf

4. http://www.nature.com/articles/nature13464.epdf?referrer_access_tok...

5. http://phys.org/news/2015-08-bacteria-secret-weapon-pesticides-anti...

6. http://www.nature.com/ncomms/2016/160219/ncomms10750/full/ncomms107...

Views: 1256

Replies to This Discussion

1255

Molecules found to counter antibiotic resistance

Genetic oddity exploited to restore drugs’ power against bacteria

https://www.sciencenews.org/article/molecules-found-counter-antibio...

--

Hundreds of Antibiotics Built from Scratch

Chemists generate variations on erythromycin in "daring" synthesis

In work described on May 18, 2016 in Nature, a team of chemists built molecules similar to the drug erythromycin, a key member of the macrolide class, from scratch. In doing so, they were able to generate more than 300 variations on erythromycin that would not have been feasible by merely modifying the original drug—the way that scientists would normally search for new variants of existing antibiotics.

The process generated several variants on erythromycin that can kill bacteria that are resistant to the antibiotic. Although much testing remains before any of the molecules could be used in people, many of them show promise, says chemist Phil Baran of the Scripps Research Institute in La Jolla, California. He adds that the work holds potential for the future of antibiotics: “The fact that you can now make deeply modified analogues in a practical way with chemical synthesis opens the door to a whole host of derivatives that could never have been dreamt of before.”

http://www.nature.com/news/hundreds-of-antibiotics-built-from-scrat...

--

Alliance of Bacterial Strains Disables Antibiotics

Two different antibiotic-resistant E. coli strains have a protective relationship in which each disables a different antibiotic, allowing both to thrive. 

cross-protection is usually seen between two animals. But Gore studies the same sort of mutualism in microbes. He and his team demonstrated the first experimental example of that cross-protective relationship in drug-resistant microbes, using two strains of antibiotic-resistant E. coli bacteria: one resistant to ampicillin, the other to chloramphenicol. 

The researchers grew the bacteria together in a test tube, in the presence of both antibiotics. And rather than succumbing to the drugs, each bacterial strain deactivated one of the two antibiotics—thus protecting the other strain. That activity led to a stable coexistence over time. Which Gore says could in theory give the bugs an opportunity to swap resistance genes, through what’s called horizontal gene transfer—one bacterium donates genetic material to another. Any such transfer could make either or both strains individually resistant to both types of antibiotics. The findings are in the Proceedings of the National Academy of Sciences. [Eugene Anatoly Yurtsev, Oscillatory dynamics in a bacterial cross-protection mutualism]

http://www.pnas.org/content/early/2016/05/17/1523317113

Revolutionary antibiotics will save the world
Russian scientists found the potential target for the revolutionary antibiotics

The Terminal Oxidase Cytochrome bdPromotes Sulfide-resistant Bacterial Respiration and Growth

http://www.nature.com/articles/srep23788

An international team of including the Lomonosov Moscow State University researchers discovered which enzyme enables Escherichia coli bacterium (E. coli) to breathe. The study is published in theScientific Reports.

Scientists discovered how the E. colibacterium can survive in the human gut - earlier the question how they breathe was a mystery to experts. Vitaliy Borisov, Senior Researcher, Doctor of Biological Sciences, Professor of the Russian Academy of Sciences, A.N. Belozersky Research Institute physical and chemical biology employee, the Lomonosov Moscow State University and one of the authors, explains that breathingE. coli uses special enzymes, which are absent in the human body. This means that the discovery of the scientists can contribute to the creation of new drugs, which will be detrimental to the bacteria without harming a human.

The energy for the vital activity of any organism comes from food, and is generated by the means of redox processes in the body. The food is converted into energy not directly but through intermediaries. First, the complex molecules are decomposed into simpler: proteins are decomposed into amino acids, fats - to fatty acids, carbohydrates - to monosaccharides. Oxidation of simpler molecules releases energy, which all is contained in the electrons.

The electrons passes to the respiratory chain with the so-called reducing equivalents (electron-carrying compound). They are NADH (nicotinamide adenine dinucleotide) and ubiquinol, also known as coenzyme Q. These two basic reducing equivalents fully cope with the processing of food: NADH is a water-soluble compound and ubiquinol is fat-soluble. Membranous enzymes accept electrons from reducing equivalents and transfer them to molecular oxygen.

The terminal cytochrome oxidase is the main membrane enzyme responsible for the human mitochondrial respiration and was thought to be used for the breath of E. coli as well. The scheme of oxidases action is simple: transferring electrons to molecular oxygen, reducing equivalents are oxidized again, and as a result "the energy currency" of the cell - the proton-moving force is generated.

'If you stop breathing, you die just because oxygen does not flow to the oxidase, and it does not produce energy,' says Vitaly Borisov.

The Escherichia coli bacterium lives in the gastrointestinal tract, where a lot of hydrogen sulfide is produced, which attenuates mitochondrial respiration. Free hydrogen sulfide inhibits cytochrome oxidase work. Its concentration exceeds several hundred times the minimum concentration required for substantial blocking of this enzyme. Hence, it seems that the E. coli bacterium cannot "breathe", but despite that the bacteria somehow survive in the intestine. The researchers assumed that the breath in the presence of hydrogen sulfide is still possible, but due to other oxidase. The fact is that the breath in people and bacteria occur in different ways. Each cell in our body "breathes" due to the work of only the cytochrome-c oxidase, others we have not. However, the E. coli bacteria has two types of oxidase: bo-type cytochrome oxidase (analogue of "human" cytochrome-c oxidase) and completely different bd-type cytochromes.

'Our hypothesis was that the bd-type oxidase (bd-I and bd-II) are more resistant to the hydrogen sulfide inhibition than the bo-type cytochrome oxidase,' commented Vitaly Borisov.

To test this hypothesis scientists needed to learn how the sulfide presence in the environment affects the growth of the E. coli bacteria cells, which have only one terminal oxidase (bd-I, bd-II or bo) in the respiratory chain. a variety of biochemical, biophysical and microbiological methods and approaches were applied, as well as the method of the intended mutagenesis.

The hypothesis was fully confirmed.

'Bo-oxidase's activity is completely inhibited by the hydrogen sulfide, while the work of the bd-oxidases remains untouched by the H2S. Thus, in order to successfully produce the main types of "the energy currency" under a high concentration of hydrogen sulfide, the intestinal microflora inhabitants should use a unique type of terminal oxidases, which is missing in the cells of humans and animals,' says Vitaly Borisov.

The discovery could be used in the future to develop medicines that regulate the intestinal microflora and relieving it from harmful bacteria. As human cells do not contain the bd-type oxidase, the question of the ability to combat disease-causing bacteria without causing harm to the human body becomes relevant. For example, the bacterium causing tuberculosis, which's primarily membrane enzyme is also a bd-type oxidase, quickly gaining resistance to classical antibiotics. Through this study there is a prospect of a new type of antibiotics "turning off" the oxygen only to the harmful bacteria cells, not to human cells.

http://www.eurekalert.org/pub_releases/2016-04/lmsu-raw042516.php

$$$$

https://www.sciencedaily.com/releases/2017/01/170131104442.htm

Scientists have for the first time determined the molecular structure of a new antibiotic which could hold the key to tackling drug resistant bacteria.

RSS

© 2017   Created by Dr. Krishna Kumari Challa.   Powered by

Badges  |  Report an Issue  |  Terms of Service