How can studying bacteria and their viruses help us find solutions to the problem of antibiotic resistance?
Antibiotic resistance presents a major threat to humanity: if we can not protect ourselves from bacterial infections, deaths from these diseases will skyrocket. Thankfully, many scientists around the world are working on combating antibiotic resistance. Among them is Professor Tracy Raivio from the University of Alberta, Canada, who is investigating how bacteria modify their envelopes and interact with specialised viruses to understand how these events could be used for our benefit.
Talk like a molecular microbiologist
Antibiotic — a drug that destroys or inhibits the growth of bacteria
Bacterium — a single bacterial cell, one of a diverse and numerous group of small, single-celled organisms found almost everywhere on Earth
Bacterial envelope — the ‘skin’ of a bacterial cell, made up of the cell membrane(s) and the cell wall
Bacteriophage — a type of virus that infects and reproduces inside bacteria
Bioinformatics — a scientific discipline that uses computer technology to collect, store and analyse biological data
Chromosome — a structure found within cells consisting of genetic material and proteins
Genome — an organism’s complete set of DNA
Virus — a tiny piece of organic material (typically a small amount of genetic material surrounded by a protein coat) that infects hosts in order to reproduce or preserve its genome through integration into the host cell’s chromosomes
When someone has a bacterial infection, the most common treatment is a course of antibiotics. However, bacteria are becoming increasingly resistant to these drugs, which is creating a huge healthcare problem. “Antibiotics are the medicines that your doctor would give you to stop the growth of a bacterial infection,” explains Professor Tracy Raivio, a molecular microbiologist from the University of Alberta. “Antibiotic resistance, sometimes called antimicrobial resistance, occurs when bacteria become insensitive to these drugs, making bacterial infections much harder to treat.” Tracy and her research team are exploring how this resistance comes about, with the aim of identifying new ways of disrupting the process and preventing antibiotic resistance becoming a global crisis.
Since Dr Alexander Fleming discovered penicillin in 1928, antibiotics have revolutionised healthcare, and many previously fatal diseases can now be treated easily and effectively. However, as scientists continue to develop new and stronger antibiotics, bacteria continue to evolve and adapt to withstand these drugs. “Some estimate that, by 2050, two million people could die every year from antibiotic-resistant infections1,” says Tracy. “This is a global problem that needs to be tackled.”
Antibiotic resistance and how to study it
A bacterium’s outer covering, which can be thought of as its skin, is called the bacterial envelope. “This is the first part of the bacterium to come into contact with anything that might be damaging or deadly to it,” explains Tracy. “Just like our skin detecting when something burns us, the envelope has sensors that detect when the bacterium is in danger.” Bacteria respond to this sensation by moving away from the danger, or by modifying their envelope to become resistant to it. “Antibiotics can damage the bacterial envelope, and the envelope’s ability to sense this damage may trigger the development of antibiotic resistance,” says Tracy. “If we are able to short-circuit these sensory responses, we may be able to make antibiotics effective again.”
Tracy’s lab is examining the relationships between the bacterial envelope and antibiotic resistance using a variety of techniques. “We do a lot of work on bacterial genetics,” says Tracy. “This involves looking for mutant bacteria with antibiotic resistance, and investigating which genes have mutated and how they have modified the envelope.” The team also uses bioinformatics and genome sequencing techniques, which involve comparing the genomes of many bacterial mutants and using computational tools to understand how genetic mutations affect their characteristics. “Alongside that, we use a lot of molecular biology techniques,” says Tracy. “Once we have identified genes of interest, we can design specific mutations and introduce them into a bacterial chromosome to see how they affect resistance.”
Tracy’s work has led to some important discoveries. “I have been studying a sensory protein in the bacterial envelope for my whole career, and we now know a lot about it,” she says. “If we can develop a drug that disrupts this protein, we could potentially disrupt antibiotic resistance.”
Bacteriophages
Antibiotics are not the only substances that are deadly to bacteria. While bacteria are small, viruses are even smaller, and certain viruses can infect bacteria and harm them. “Viruses that infect bacteria are called bacteriophages,” says Tracy. “Bacteriophages attach to the bacterial envelope and inject their DNA into the cell, taking over its internal machinery, multiplying rapidly and ultimately killing the bacterium.” This ability makes bacteriophages a potential alternative to antibiotics, if they can be harnessed effectively. Tracy and her research team are studying how bacteriophages interact with the bacterial envelope, which could help them to design and utilise modified bacteriophages to treat bacterial infections.
However, bacteriophages do not always kill their bacterial host straight away. Sometimes, the bacteriophage DNA becomes integrated into the bacterium’s own chromosome and is passed down to future generations when the bacterium replicates. After lying dormant for some time, conditions in the bacterium can change, leading to the virus removing itself from the bacterial chromosome, multiplying and killing its host.
“As they spread and infect many bacteria, bacteriophages can ‘pick up’ genes from the bacterial cells that they infect,” explains Tracy. “When a bacteriophage infects a new bacterium, it inserts these genes into the bacterium’s genome.” This allows genes to be transferred between different bacteria, and the recipient may be able to use these genes in new ways: for example, by modifying its envelope to develop antibiotic resistance. This means that while bacteriophages could help combat antibiotic resistance, they may also contribute to it.
Reference
https://doi.org/10.33424/FUTURUM563
A rendering of a bacterial envelope, a complex structure that acts as a bacterium’s ‘skin’. In this rendering, the parts that make up the envelope, including the outer membrane, the inner membrane and various proteins, are seen in green. Illustration by David S. Goodsell, RCSB Protein Data Bank. doi: 10.2210/ rcsb_pdb/goodsell-gallery-028.
A PhD student in Tracy’s lab, Kat Pick, accidentally discovered a new bacteriophage in a strain of E. coli bacteria that had been isolated from a mouse’s gut. “Kat has discovered that this bacteriophage helps the E. coli survive in its natural environment,” says Tracy. “What’s more, this bacteriophage interacts with genetic material within the E. coli’s chromosome that has been left behind by other bacteriophages from previous infections.” These ‘genetic remnants’ may be the key that allows a bacterium to develop antibiotic resistance.
“We have never seen such an intricate web of interactions before,” says Tracy. “By studying them, we hope to learn more about how bacteria adapt to their natural environments so that we can discover new ways to short-circuit antibacterial resistance or develop new antibiotics.”
1 Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050, Naghavi, Mohsen et al., The Lancet, Volume 404, Issue 10459, 1199 – 1226
Professor Tracy Raivio
Department of Biological Sciences, Faculty of Science, University of Alberta, Canada
Fields of research: Molecular biology, microbiology, genetics, antibiotic resistance
Research project: Studying bacterial envelopes and interactions with bacteriophages to understand the mechanisms underlying antibiotic resistance
Funders: Canadian Institutes of Health Research (CIHR), Natural Sciences and Engineering Research Council of Canada (NSERC)
About molecular microbiology
Molecular microbiology is the study of the molecules that make up microorganisms and how they interact. This involves studying the structures, functions and interactions of these molecules. Most molecular microbiology research is lab-based, and often has the potential for application in healthcare and other industries.
A vital field of study within the discipline is antibiotic resistance, a major societal issue that requires the research of molecular microbiologists to combat it. “Our lab is focused on discovery, but the ultimate goal is to apply the knowledge gained to improve human health,” says Tracy. “All our research is highly collaborative and builds on existing research from a whole host of talented people.”
One of the biggest challenges for molecular microbiology is translating lab discoveries into useful advances for society. “A big next step for our research is to see if our findings hold true in more realistic environments,” says Tracy. “There is a big difference between disrupting antibiotic resistance in controlled lab conditions and disrupting antibiotic resistance in the far more complex systems of the real world.” For example, an antibiotic might overpower lab-grown, ‘domesticated’ bacteria but be ineffective against ‘wild’ bacteria in the human gut. Additionally, a new antibiotic might have unexpected consequences such as killing helpful bacteria that keep us healthy.
As with many fields, the rise of artificial intelligence (AI) provides tantalising opportunities for molecular microbiology. For example, Tracy’s team has used AI to predict the structure of an important protein found in E. coli, opening up new avenues of research. “Advances in AI will boost our ability to understand all sorts of things,” says Tracy. “I would love to work with scientists who are using AI to predict and design new antibiotics, so that we could share our research and work together to tackle the issue of antibiotic resistance.”
Pathway from school to molecular microbiology
Biology, chemistry, mathematics and physics will prepare you for a career in molecular microbiology or a related field. Given the rise of AI and bioinformatics, subjects like computer science, statistics and coding will also prove helpful.
Many universities run postgraduate degrees focused on molecular microbiology. Undergraduate courses that can prepare you for a career in molecular microbiology include molecular biology, microbiology, biochemistry, biology, cell biology, medicine and biotechnology. Tracy notes that her lab works with lots of people who study related disciplines, including biochemistry, the microbiome and animal medicine.
The University of Alberta runs science outreach activities for high school students via ‘The Shack’, including campus tours, summer camps, science demonstrations and a host of other events.
Explore careers in molecular microbiology
To prepare for a career in this field, learn more about the issues molecular microbiologists are tackling. For example, World Antimicrobial Resistance Awareness Week is a global annual campaign to provide education about antimicrobial resistance and promote best practices. There are lots of resources to help you get involved and learn more on their website.
This podcast from the American Society for Microbiology discusses careers in antimicrobial resistance.
Meet Tracy
As a kid, I loved nature and was fascinated by biology. I spent a lot of time outdoors with my family, and I remember wondering: How do leaves know when to change colour? How do trees know when it’s spring? How do rocks know which shape to form? Though I wasn’t interested in microbiology specifically, nature always captured my curiosity.
I love figuring out how things work. I want to understand the nitty-gritty details, and I am grateful to have the privilege of spending my career doing exactly that. I love learning about what other people are researching, their approach to finding answers and their life experiences. I find that listening to how people approach problems in other disciplines is highly instructive.
I wish I had talked to more people as a younger scientist. Finding the courage and opportunities needed to do that can be tricky, but it’s the best way to find answers to questions and engage in interesting things. People usually love to talk about their interests, what they’re doing, why they’re doing it, and how they’re doing it.
To unwind from work, I love reading. I am passionate about learning new things, and always have a pile of books to get through. I also love being outside in nature in any season, ideally sharing my time with the people that are closest to me.
Tracy’s top tips
1. Find opportunities to talk to people that are doing what you’re interested in. Don’t be afraid to ask questions.
2. Most future scientific careers are likely to use artificial intelligence and machine learning, so aim to get a handle on how to use them.
3. Figuring out your place in the world can be scary, but it’s important to pursue the things that you’re passionate about and that excite you. Focus on taking the opportunities that present themselves.
Do you have a question for Tracy?
Write it in the comments box below and Tracy will get back to you. (Remember, researchers are very busy people, so you may have to wait a few days.)
Learn about other ways of tackling antibiotic resistance:
www.futurumcareers.com/the-need-for-antimicrobial-peptides-in-a-world-of-antibiotic-resistance
0 Comments