Antibiotic Resistance: Everything You Need To Know
If youre a fan of apocalyptic disaster movies, youll be familiar with all manner of things that might bring about the fall of civilisation: asteroid strikes, deadly viruses, alien invasions, nuclear armageddon. Perhaps even an outbreak of zombies.
Experts now believe that the spread of drug-resistant bacteria is probably the single greatest threat to society greater even than the dangers posed by global terrorism, climate change and anything youll see at the cinema.
There are signs that this antibiotic apocalypse is already upon us: in Europe and the US alone, at least 50,000 people die each year from infections that dont respond to conventional treatment.
Why Is Antibiotic Resistance A Problem
Antibiotic resistance happens when bacteria survive and continue causing infection despite treatment with an antibiotic the bacteria are no longer sensitive to that antibiotic.
Because the antibiotic no longer works against the resistant bacteria:
- infections take longer to heal
- infections can get worse and lead to more serious problems
- infections are more likely to spread to other people. Because bacteria are resistant, the antibiotic may not work for other people, further spreading the problem
Sometimes it is possible to use another antibiotic to which bacteria arent resistant. However, it may not work as well, and it could have side effects. Also, bacteria may eventually become resistant to this antibiotic too.
For these reasons, antibiotic resistance is a major threat to human health. There is concern that in time, therell be bacterial infections that just cant be treated.
What Does Antibiotic Resistance Mean For You Your Family And The Community
Antibiotic resistance is a major concern because it means some infections will become more difficult, and sometimes impossible, to treat. If you or someone in your family develop an antibiotic-resistant infection:
- you may have the infection for longer
- you may be more likely to have complications from the infection
- you could remain infectious for longer and pass your infection to other people.
Infections caused by antibiotic-resistant bacteria are harder to treat, usually last longer, often result is longer stays in hospital and are associated with more complications. In serious cases they can cause death. Doctors have to use to less conventional antibiotics or a combination of different antibiotics to treat these infections. These are usually more costly and can have more-serious side effects. In New Zealand, the occurrence of antibiotic-resistant bacteria is increasing. Examples of antibiotic-resistant bacteria include:
- Methicillin-resistant Staphylococcus aureus a group of bacteria that are resistant to commonly used penicillin-like antibiotics
- Extended spectrum beta-lactamases chemicals produced by some bacteria that prevent certain antibiotics from working.
- Vancomycin-resistant enterococci a group of bacteria that are resistant to the antibiotic vancomycin.
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References And Suggested Readings
How Do Prokaryotes Develop Antibiotic Resistance
Antibiotic resistance 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. Antibiotics kill or inhibit the growth of susceptible bacteria.
Also, how do antibiotics affect prokaryotic cells? Antibiotics are simply chemicals that kill prokaryotic cells but do not harm eukaryotic cells. They are natural chemicals produced by fungi and bacteria that act to control their bacterial competitors. For example, streptomycin stops protein synthesis in prokaryotic cells by binding to their unusual ribosomes.
Also to know, what are the two ways that bacteria can acquire antibiotic resistance?
There are two main ways that bacterial cells can acquire antibiotic resistance. One is through mutations that occur in the DNA of the cell during replication. The other way that bacteria acquire resistance is through horizontal gene transfer.
What are the four mechanisms of antibiotic resistance?
Resistance to antibiotics can be caused by four general mechanisms and bacteria can develop resistance by mutating existing genes, or by acquiring new genes from other strains or species.
Why Is This Issue Important Why Should I Care
Without effective antibiotics many routine treatments will become increasingly dangerous. Setting broken bones, basic operations, even chemotherapy and animal health all rely on access to antibiotics that work.
When infections can no longer be treated by first-line antibiotics, more expensive medicines must be used. A longer duration of illness and treatment, often in hospitals, increases health care costs as well as the economic burden on families and societies.
Antibiotic resistant infections are one of the leading threats to human health and modern medicine. The World Health Organisation and international governments have stated that urgent measures are needed to avert the crisis we face.
If new, powerful antibiotic drugs are not discovered, we may return to the pre-antibiotic era.
Professor Mathew Upton
Infection Control In Hospitals
Standard precautions in hospitals are work practices that provide a basic level of infection control for the care of all people, regardless of their diagnosis or presumed infection status.These precautions should be followed in all hospitals and healthcare facilities and include:
- good personal hygiene, such as hand washing before and after patient contact and the appropriate use of alcohol-based hand rub solutions
- the use of barrier equipment such as gloves, gowns, masks and goggles
- appropriate handling and disposal of sharps and clinical waste
- aseptic techniques.
Implementing standard precautions minimises the risk of transmission of infection from person to person, even in high-risk situations.
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I Modifications Of The Antibiotic Molecule
One of the most successful bacterial strategies to cope with the presence of antibiotics is to produce enzymes that inactivate the drug by adding specific chemical moieties to the compound or that destroy the molecule itself, rendering the antibiotic unable to interact with its target.
I.A. Chemical alterations of the antibiotic
The production of enzymes capable of introducing chemical changes to the antimicrobial molecule is a well-known mechanism of acquired antibiotic resistance in both gram-negative and gram-positive bacteria. Interestingly, most of the antibiotics affected by these enzymatic modifications exert their mechanism of action by inhibiting protein synthesis at the ribosome level . Many types of modifying enzymes have been described, and the most frequent biochemical reactions they catalyze include i) acetylation , ii) phosphorylation , and iii) adenylation . Regardless of the biochemical reaction, the resulting effect is often related to steric hindrance that decreases the avidity of the drug for its target, which, in turn, is reflected in higher bacterial MICs.
Representation of different types of aminoglycoside-modifying enzymes and their nomenclature
A, amikacin G, gentamicin I, isepamicin K, kanamycin N, netilmicin S, sisomicin T, tobramycin.
Modified from Appl Microbiol Biotechnol 70:140150.
I.B. Destruction of the antibiotic molecule
Schematic representation of -lactamases
¥ Ambler class D enzymes belong to the functional group/subgroup 2d.
Mechanistic Basis Of Antimicrobial Resistance
In order to provide a comprehensive classification of the antibiotic resistance mechanisms, we will categorize them according to the biochemical route involved in resistance, as follows: i) modifications of the antimicrobial molecule, ii) prevention to reach the antibiotic target , iii) changes and/or bypass of target sites, and iv) resistance due to global cell adaptive processes. Each of these mechanistic strategies encompasses specific biochemical pathways that will be described in detail in the reminder of the chapter. Of note, we will focus the discussion on the most relevant mechanisms giving examples that have relevant clinical impact.
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Modify Or Bypass The Target Of The Antibiotic:
- Camouflage the target. Changes in the composition or structure of the target in the bacterium can stop the antibiotic from interacting with the target. Alternatively, the bacteria can add different chemical groups to the target structure, in this way shielding it from the antibiotic.
- Express alternative proteins. Some bacteria are able to produce alternative proteins that can be used instead of the ones that are inhibited by the antibiotic. For example, the bacterium Staphylococcus aureus can acquire the resistance gene mecA and produce a new penicillin-binding protein. These proteins are needed for bacterial cell wall synthesis and are the targets of -lactam antibiotics. The new penicillin-binding protein has low affinity to -lactam antibiotics and is thus resistant to the drugs, and the bacteria survive treatment. This type of resistance is the basis in MRSA .
- Reprogram target. Sometimes bacteria can produce a different variant of a structure it needs. For example, Vancomycin-resistant bacteria make a different cell wall compared to susceptible bacteria. The antibiotic is not able to interact as well with this type of cell wall.
How Does Antibiotic Resistance Happen
Bacteria can become resistant to antibiotics in several ways.
- Some bacteria can change their outer structure so the antibiotic has no way to attach to the bacteria it is intended to kill.
- Some bacteria can ‘neutralise’ an antibiotic by changing it in a way that makes it ineffective.
- Others have mechanisms that pump an antibiotic back outside of the bacteria before it can work.
- Bacteria can also become resistant through mutation of their genetic material. After being exposed to antibiotics, sometimes bacteria can survive by finding a way to resist the antibiotic. If even one bacterium becomes resistant to an antibiotic, it can then multiply and replace all the bacteria that were killed off.
The spread of antibiotic resistance occurs when resistant strains of bacteria are passed from person to person and from non-human sources in the environment, including food.
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Are There Alternatives To Antibiotics
Scientists are starting to combine antibiotics with compounds that disrupt whatever adaptation the resistant bacteria have developed.
For example, if a bacterium has started producing a protein that stops an antibiotic entering its membrane, researchers can develop a decoy compound to block that protein. The patient takes a combination of the antibiotic and the decoy, and the antibiotic suddenly works again.
Another alternative to conventional antibiotics is a treatment that has been used in Russia and Eastern Europe since the 1940s but for a long time was not taken seriously in the West.
Known as phage therapy, it uses viruses to hijack bacteria and destroy them from the inside. While it may sound dangerous, the viruses used known as bacteriophages naturally attack bacteria and bacteria only.
Other potential avenues for research include drugs that help the immune system to identify and attack bacteria, the use of bioengineered nanoparticles or viruses to bombard bacteria, and the use of probiotic, friendly bacteria to outcompete the nasty ones.
The problem with all of these potential solutions? Bacteria could develop resistance to any of these treatments eventually, too.
Historical Timeline Of Antibiotics
- Louis Pasteur unknowingly described the first antibiotic in 1877 when he observed that certain bacteria release substances that kill other bacteria
- In 1909, Paul Ehrlich discovered arsphenamine , an arsenic compound that kills Treponema palladium, the bacterium causing the sexually transmitted disease, syphilis.
- In 1928 Alexander Fleming discovered that a mold inhibited the growth of staphylococcal bacteria and named the substance it produced “penicillin” .
- It was not until 1940 that Howard Florey and Ernst Chain isolated the active ingredient in Fleming’s mold.
- With wide-scale production of penicillin, the use of antibiotics increased, leading to an average eight-year increase in human life span between 1944 and 1972. Unfortunately, many bacterial species continued to survive penicillin treatment due to their resistance mechanisms.
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How Worried Should We Be
Pretty worried! Many strains of bacteria have acquired resistance to more than one type of antibiotic.
These strains of bacteria, known as multidrug resistant organisms or superbugs, are already putting a strain on the worlds healthcare systems. Prof Dame Sally Davies, former chief medical officer for the UK, said that the golden era of ever-increasing life expectancy may soon give way to an era where mortality rates start to increase.
She told a government inquiry on antibiotic resistance that she was far more worried about dying in an operating theatre during a routine operation than climate change.
Hospitals are struggling to rid wards of multi-drug resistant bacteria such as MRSA , while extensively drug-resistant tuberculosis has now been identified in 100 countries, causing over 200,000 deaths each year.
In E. coli bacteria, a common cause of food poisoning, resistance to antibiotics is now so widespread that conventional treatment is ineffective in more than half of patients.
And strains of bacteria have been found that are resistant to our last resort antibiotics.
Treating patients who have these dangerous bacteria is difficult, hazardous and expensive. Experts have predicted that if trends continue, existing antibiotics could be almost useless in as little as 20 years.
Microbial Diagnostics And Infection Control Research Group
There is a global drive to not only discover new antibiotics to combat bacteria which were previously susceptible to antibiotic treatment, but also to develop new types of diagnostics that can help diagnose infection at the point of care.
Dr Tina Joshi’s research focuses on designing low cost and rapid point of care nucleic acid-based biosensor assays for detection of AMR resistance genes and other pathogens that work within minutes from sample to result. This research is multidisciplinary and encompasses the engineering, biology, informatics and chemistry disciplines.
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How Do Antibiotics Work
Antibiotics are chemicals that disrupt key processes in bacterial cells. To be safely used as a drug, they must specifically affect bacterial cells without damaging human tissue.
The first modern antibacterial, penicillin, was discovered in 1928 by Alexander Fleming. Produced by a fungus found in mould, penicillin causes the walls of bacterial cells to fail.
Human cells do not have these rigid cell walls, so are unaffected by penicillin, and many similar drugs have been developed over the decades.
Other antibiotics interfere with processes that are essential for bacteria to grow, such as the production of proteins, DNA, or energy.
Scientific terms explained
AMR AMR, or antimicrobial resistance, is a broad term that includes the emergence of resistance in bacteria, as well as in other microorganisms such as viruses and fungi.
Beta-lactamase Bacteria that can produce beta-lactamase are a major threat to healthcare systems worldwide. This chemical blocks the action of a key family of antibiotics that act on the bacterial cell wall.
Horizontal Gene Transfer As well as passing on DNA to successive generations, bacteria can also exchange DNA with unrelated microorganisms nearby. This allows them to share useful genes, helping resistance spread from one species to another.
MDROs Multi-drug resistant organisms are strains of bacteria that are resistant to lots of antibiotics. Some are resistant to last resort drugs.
How Did Antibiotic Resistance Develop
How did antibiotic resistance develop? Bacteria develop resistance mechanisms by using instructions provided by their DNA. Often, resistance genes are found within plasmids, small pieces of DNA that carry genetic instructions from one germ to another. This means that some bacteria can share their DNA and make other germs become resistant.
How did antibiotic resistance start? Antibiotic resistance evolves naturally via natural selection through random mutation, but it could also be engineered by applying an evolutionary stress on a population. Once such a gene is generated, bacteria can then transfer the genetic information in a horizontal fashion by plasmid exchange.
How does antibiotic resistance develop and spread? When exposed to antibiotics, susceptible bacteria are killed while excessive antibiotic use or their use for the wrong reasons can cause bacteria to become resistant and continue to grow and multiply. These resistant bacteria may spread and cause infections in other people.
How does poor hygiene cause antibiotic resistance? Poor water, sanitation and hygiene leads to the spread of infectious diseases, which in turn leads to increased use of antibiotics. To reduce use is critical to limit emergence and spread of antibiotic resistant bacteria.
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Understanding And Treating Drug
Professor Upton and his team study pathogens that cause drug resistant infections. A particular focus is on urinary tract infections which are one of the most common bacterial infections and the cause of enormous levels of antibiotic prescription, much of which is not necessary or justified.
Professor Upton said:
We have significant expertise in analysis of the genetic relationships of these bacteria , which helps us understand the factors that lead to development of antibiotic resistance and the way the infections are spread.We use the Galleria mellonella larvae infection model, cell culture and high-resolution proteomic methods to analyse the pathogenicity of these bacteria. By understanding the way that these bacteria cause disease and avoid the action of our immune system, we aim to identify new targets for therapeutic drugs and vaccines.
Ways That Bacteria Acquire Resistance
There are two main ways that bacterial cells can acquire antibiotic resistance. One is through mutations that occur in the DNA of the cell during replication. The other way that bacteria acquire resistance is through horizontal gene transfer. There are three different ways in which this can occur, but in each case genetic material is transferred from antibiotic-resistant bacteria to other bacterial cells, making them resistant to antibiotics as well. Once bacterial cells acquire resistance, exposure to antibiotics kills off non-resistance bacteria, while the antibiotic-resistant bacteria proliferate.
To learn more about antibiotic resistance, check out The Antibiotic Resistance Action Center.
ARAC was created to preserve the effectiveness of antibiotics by engaging in research, advocacy and science-based policy. Follow ARAC on, and
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