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Resistance: Evolution and the Environment

Written by Mateusz Faltyn, Honours Bachelor of Arts and Science Candidate, McArthur Lab

Dr. Gerry Wright’s lab is engaged in efforts to discover new antibiotics and antibiotic alternatives such as adjuvants and is interested in exploring the mechanism, diversity, and evolution of antibiotic resistance.

 

Understanding the origins and evolution of resistance, the molecular mechanisms of resistance, the mobilization of resistance, and the characteristics of successful antibiotic-resistant pathogens is critical; without this knowledge, drug discovery will be hampered by ancient resistance mechanisms that have survived the scrutiny of natural selection. In the era of evolving antibiotic resistance, the various projects of the Wright Lab continue to develop and evolve.

A central objective of principal investigators within both the David Braley Centre for Antibiotic Discovery (DBCAD) and Institute for Infectious Diseases Research (IIDR) at McMaster University is to address the rising global public health problem of antibiotic resistance. While there are numerous ways to approach this problem, several researchers within the DBCAD and IIDR apply one or both of two research strategies: studying the molecular mechanisms of antibiotic resistance, as well as identifying new antibiotics and antimicrobial strategies.

Research guided by Dr. Gerry Wright, Scientific Director of both the DBCAD and IIDR and University Distinguished Professor of the Department of Biochemistry and Biomedical Sciences, applies both strategies simultaneously to better combat antibiotic resistance. Although the Wright Lab is involved in numerous research projects that aim to further our understanding of antimicrobial resistance, one theme that links many of the individual projects together is the origin and evolution of antibiotic resistance. To develop a more clear comprehension of the emergence and spread of antibiotic-resistant mechanisms, one must scrutinize the selective forces that have shaped the evolution of the “Antibiotic Resistome” – a term coined by the Wright Lab to describe the collection of all antibiotic resistant genes – from its origin to the modern day.

In contemporary antibiotic resistance literature, it is evident that most antibiotics are derived from bacteria living in the soil. This has two implications for antibiotic resistance. First, the organism which makes the antibiotic cannot be susceptible to it. This necessitates the evolution of resistance genes alongside production. Second, other bacteria which inhabit the same ecological niche have been exposed to antibiotics for millions to billions of years, allowing these bacteria to also develop resistance. Scientists did not always believe that soil organisms are often highly resistant to antibiotics and that some of these resistance genes could be spread to pathogens; the Wright Lab played a significant role in providing evidence for this paradigm shift.

“Resistance is readily detected in soil, aquatic, atmospheric, and built environments. Soils are likely the major reservoir of resistance genes and source of their diversity, given the density of microbial species there. Wild and domestic animals are also sources of resistance genes and microbial species that are shared with humans, including many that cause disease. The selection and mobilization of resistance elements coincident with antibiotic use results in gene flow from the environment to the pathogens that cause disease.”

In 2011, the Wright Lab published a paper in Nature titled Antibiotic resistance is ancient. This paper revolutionized the way scientists looked at the history of antibiotic resistance. Prior to this work, many researchers subscribed to the notion that antibiotic resistance in all bacteria (pathogenic and environmental) is a modern phenomenon, only emerging in the 20th century due to the rise in prescription antibiotics. This view of antibiotic resistance was supported by the fact that an overwhelming majority of pathogenic microbes from the pre-antibiotic era were susceptible to antibiotics. After extensive targeted metagenomic analyses of ancient DNA, the Wright Lab challenged this paradigm by synthesizing antibiotic resistance genes that were over 30,000 years old to show that they could confer resistance. This paper provided conclusive evidence that antibiotic resistance is indeed a naturally occurring process, the paradigm that most scientists hold to this date.

Skipping ahead to 2014, Perry, Westman, and Wright published an article in Current Opinion in Microbiology titled The antibiotic resistome: what’s new? The paper set out to revisit the theoretical framework of the antibiotic resistome: the origin of the resistome is ancient yet it is dynamic and constantly expanding. This expansion is occurring in ways that are both obvious and obscure. Scientists have identified most of the genes which confer resistance in the clinic; however, environmental bacteria are host to a far wider variety of resistance genes. These hidden genes still pose a potential threat to public health through the sharing of the resistome between the clinic and the environment. The authors highlighted the need for the improved understanding of how a given resistance gene evolves in the environment.

Moving along to 2017, Lessons from the Environmental Antibiotic Resistome was published by current PhD candidate Matthew Surette and Dr. Wright. As the name suggests, this review focused on the largest source and reservoir of antibiotic-resistant genes – the environment. After nearly a century of introducing thousands of tons of antibiotics into agricultural soils and animals, it is evident that microbes are responding accordingly via natural selection. This is without much of a surprise to those who are aware of the ability of bacteria to acquire antibiotic resistance, an ability that appears to be millions if not billions of years old. According to the review, antibiotic resistance is a “One Health problem, i.e., one that intricately links humans, animals, and the environment. The environments that microbes inhabit—soil, water, air, animal microbiomes—are a vast reservoir of genes capable of responding to all conceivable antibiotics. Mobilization of these genes into pathogens is only a matter of time, and there are no irresistible antibiotics”.

 

About the Author

Mateusz Faltyn, Honours Bachelor of Arts and Science Candidate

Mateusz is entering his third year in the Honours Bachelor of Arts and Science Undergraduate program at McMaster University. Currently, he is a member of Dr. Andrew McArthur’s lab. Mateusz enjoys reading and coding, as well as watching Game of Thrones.

 

Author:

Christy Groves