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

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.

New research: Deep learning AI discovers surprising new antibiotics (7). The Harvard-MIT team used a new type of deep learning AI called graph neural networks for drug discovery. The AI method used by the team describes chemicals as a network of atoms, which gives the algorithm a more complete picture of the chemical than text descriptions can provide.

Yet deep learning alone is not sufficient to discover new antibiotics. It needs to be coupled with deep biological knowledge of infections.

The Harvard-MIT team meticulously trained the AI algorithm with examples of drugs that are effective and those that aren't. In addition, they used drugs that are known to be safe in humans to train the AI. They then used the AI algorithm to identify potentially safe yet potent antibiotics from millions of chemicals.

Unlike people, AI has no preconceived notions, especially about what an antibiotic should look like. Using old-school AI, my lab recently discovered some surprising candidates for treating tuberculosis, including an anti-psychotic drug. In the study by the Harvard-MIT team, they found a gold mine of new candidates. These candidate drugs do not look anything like existing antibiotics. One promising candidate is Halicin, a drug being explored for treating diabetes.

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...

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...

7. https://techxplore.com/news/2020-02-deep-ai-antibiotics.html?utm_so...