Origins of Antibiotic Resistance

By Sarah MooreReviewed by Sophia Coveney

Antibiotics are heavily relied upon by medical professionals around the world to treat a range of conditions, some life-threatening, as well as by the agricultural industry to prevent disease and sickness spreading among animals.

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Our strong reliance on antibiotics, however, is also leading to its downfall. As the use of antibiotics increases, as does antibiotic resistance, rendering the medicine ineffective and leaving patients without adequate treatment options as the bacterium involved in their illness becomes resistant to the available antibiotics. It is vital to understand how antibiotic resistance has emerged, and what we can do to prevent it.

Increase in use of antibiotics linked with increased resistance

Penicillin, the first true antibiotic was discovered in 1928 by Alexander Fleming. In almost a century that has passed since then, antibiotics have been developed to treat a wide range of conditions, including acne, bronchitis, conjunctivitis, ear infections, sexually transmitted diseases, streptococcal pharyngitis, tonsillitis, upper respiratory tract infection, urinary tract infection, and various other infections.

Research conducted by the World Health Organization has confirmed that antibiotic use is rapidly increasing, with Access antibiotics (first-line or second-line therapies) seeing a use per capita increase of 26.2% between 2000 and 2015, and use of Watch antibiotics (for use only with specific indications due to higher resistance potentials) increasing by 90.9% over the same period.

This increase in use is concerning, given that the European Centre for Disease Prevention (ECDC) has called out unnecessary prescriptions as one of the main causes of antibiotic resistance. As the world relies more and more on antibiotics, the efficacy of this treatment remains threatened by the ability of the bacteria the underlie various conditions to become resistant to the antibiotics.

Here, we discuss the origins of such resistance.

Main origins of antibiotic resistance

The ECDC recently outlined what they believe are the three main causes of antibiotic resistance. Their research attributes three scenarios of antibiotic misuse that are known to contribute to antibiotic resistance.

The first misuse scenario is the unnecessary prescription of antibiotics for viral infections. Antibiotics work only on bacterial infections and have no impact on viral infections. The second misuse of antibiotics that leads to antibiotic resistance is misdiagnosis.

Often, when the exact micro-organism causing the illness is unknown, doctors prescribe an antibiotic that targets a wide range of bacteria, killing off a broad-spectrum rather than the specific bacteria related to the condition. Finally, the ECDC highlights the incorrect use of antibiotics as the third misuse scenario leading to antibiotic resistance. Incorrect use refers to incorrect durations, doses, or frequencies. This can be due to incorrect prescriptions or incorrect patient use.

The above are the most common causes of antibiotic resistance relating to their use in the modern healthcare system. Next, we discuss the biological mechanisms of antibiotic resistance and outline how resistance has become possible via various routes.

The mechanisms of antibiotic resistance

Bacteria can be naturally resistant to particular antibiotics; others, however, develop resistance through genetic mutations induced via exposure to antibiotics. Therefore, resistance can be innate or acquired. Antibiotic resistance also has the opportunity to spread, given the ease of exchanging the material relating to resistance between bacteria species.

Research has outlined the four basic mechanisms of antibiotic resistance: limiting uptake of a drug; modifying a drug target; inactivating a drug; active drug efflux. Mechanisms that underlie intrinsic resistance are limiting uptake, drug inactivation, and drug efflux. Those underlying acquired resistance are drug target modification, drug inactivation, and drug efflux.

All of these resistance mechanisms are believed to have evolved from resistance genes existing in organisms producing antibiotics.

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Resistance genes

Determining the origins of antibiotic resistance genes has proved challenging to scientists because the use of antibiotics began before the biochemical and molecular basis of antibiotic resistance was established.

Antibiotic was not reported into the 1940s, over a decade following the first use of penicillin. Resistance was first recorded in the bacterial species of streptococci and gonococci. Resistance first presented a major issue to antibiotic use with the treatment of tuberculosis (TB). Currently, antibiotic resistance remains a major public health threat and a contributor to antimicrobial resistance worldwide.

Mutations naturally occur in DNA. This is the basis of evolution. Mutations that are favorable are those most likely to survive and, therefore, over time they become more common. In bacteria, favorable mutations can spread rapidly as they are mobilized via insertion sequences and transposons, allowing them to transfer to different bacterial species.

Therefore, a mutation that allows a bacterium to survive antibiotic exposure can then pass on this genetic advantage to other bacteria, even that of different species, at alarming rates. For this reason, it is vital to prevent scenarios that support this scenario in order to protect human health.

Action is required to prevent the spread of antibiotic resistance

Heath organizations worldwide stress the importance of taking action to reduce the rate of evolution and spread of genes that cause antibiotic resistance. One of the best strategies for doing this is to avoid the misuse of antibiotics as outlined above.

Further Reading

• All Antibiotic Resistance Content
• The Global Spread of Antibiotic Resistance
• The Rising Threat of Antimicrobial Resistance
• Antibiotic vs Antimicrobial Resistance
• Global travel and antibiotic resistance