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How can we use genomics to prevent antimicrobial-resistant superbugs?

The spread of antimicrobial resistance is a serious but predictable concern in healthcare. Researchers used whole genome sequencing to determine how antimicrobial resistant outbreaks occur and how to prevent them.

One of the greatest medical discoveries of the 20th century was penicillin. Before the discovery of antibiotics, bacterial infections were seen as a near guarantee of death. However, penicillin was the first antibiotic discovered to combat infection and soon became the standard in medical practice which saved countless lives. As penicillin’s popularity spread across the world, new generations of antibiotics were produced to gain territory in the war against microbial infections. However, the rise of antimicrobial resistance is now threatening our peaceful intermission.

Antimicrobial resistance is the ability of a bacterial cell to tolerate antibiotics. The stronger their resistance, the stronger their ability to tolerate antibiotics and infect the individual as normal. All antimicrobial-resistant bacteria have a threshold of antibiotic they can sustain before they are affected, but this is typically too high for safe medical doses. This makes antimicrobial resistance a serious threat to public health.

In recent decades, there have been outbreaks of antimicrobial-resistant bacteria which have prompted researchers to ask how these outbreaks occur and how we can better prevent them. Modern advances in whole genome sequencing have now allowed researchers to track antimicrobial-resistant evolution across the world. In a review published in the prestigious journal Science, researchers compiled the results of tracking key antimicrobial resistant bacteria across the globe.

The emergence of antimicrobial resistance

Antimicrobial resistance emerges from two evolutionary factors: genetic mutations and environmental pressures. As bacteria divide, small random mutations appear in the genome. These mutations are usually harmless or harmful to the bacteria. However, occasionally, these mutations can be beneficial which will give them new or enhanced abilities, such as antimicrobial resistance. Since the origin of these mutations are genetic, antimicrobial resistance can be passed down to future generations of bacteria. This lineage of antimicrobial resistance is called a clone.

Most bacteria in the wild are a mixture of different clones, with only a small population of them being antimicrobial resistant. It is only when antibiotics are used that the ones without antimicrobial resistance die off and the ones that do survive which causes the emergence of an antimicrobial resistance infection.

Researchers have found that most of these antimicrobial resistance clones are quickly eliminated due to trade-offs in antibiotic resistance. However, some of these antibiotic-resistant clones are strong enough to stay within the population and spread. In fact, researchers discovered that the primary factor in bacteria spreading geographically is due to antimicrobial resistance. This was observed in the worldwide spread of methicillin-resistant Staphylococcus aureus after attaining certain genetic mutations.

Hospitals are prime targets for superbugs About 1 in 10 hospital patients contract an infection that originated from the hospital. Hospitals are prime targets for housing bacterial superbugs that are resistant to multiple antibiotics making them a serious threat. Researchers analyzing whole-genome sequencing data have found that antimicrobial resistant bacteria emerge predictably within hospitals depending on where the patient was staying in the hospital and what antibiotics were prescribed.

Indeed, the researchers found superbugs emerged from patient infections which spread locally within the hospital then internationally. An example was seen in the superbug K. pneumonia ST258, which is resistant to all β-lactam antibiotics, where it originated in the United States and then spread throughout hospitals in 2005. Yet by 2009, it had spread to Israel and across the continent into Europe. It can now be found in South America, Asia, and Australia.

Whole genome sequencing can help with preventative care

The spread of antimicrobial resistance is a serious but predictable concern in healthcare. Through whole-genome sequencing, researchers are able to gather data on how bacteria adapt to medications. This can provide healthcare providers with the tools and knowledge to fight against resistance. Specifically, whole genome sequencing can help researchers to develop strategies to minimize the chance that the resistant bacteria will spread during individual treatments.

Researchers using whole genome sequencing found antimicrobial resistant bacteria originate from local events depending on antibiotic use and location of treatment within hospitals. Researchers suggest that a practical approach to countering the emergence of antimicrobial resistance is to include antibiotic rotations within hospitals. While this means some patients will be given less than ideal antibiotics for their specific infection, it will lower the environmental pressures for local antimicrobial resistance emergence. The researchers also warn that international collaboration is necessary to prevent hospital superbugs from spreading.

Institutions such as The Global Microbial Identifier Project and the World Health Organization are key advocates for promoting antimicrobial resistance awareness and prevention around the world. Since antimicrobial resistance can easily spread internationally, this is a global health issue that must be addressed by all nations.

Written by Aaron Kwong, MSc

Reference: Baker, S., Thomson, N., Weill, F.-X. & Holt, K. E. Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens. Science (80-.).360, 733–738 (2017).



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