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How do researchers use bacterial genome sequences?

Several researchers from the Wellcome Trust Sanger Institute explain how they use bacterial genome sequences in their work.
So I work with bacteria that live in the nasal pharynx, which is the area at the back of the nasal passages. And recently I’ve been focusing on a new species of bacteria that we’ve seen in various studies from different countries around the world that seems to be fairly high prevalence in very small children under the age of five. And we’re interested in this species, but it’s uncultured. So although it seems to grow quite well in people, we can’t grow it in the lab. We decided to try and solve this problem using genomics. So we extracted DNA directly from a sample taken from someone’s nose.
And we sequenced it, and pulled out the genome that we were interested in from the mix of species. And what we’re planning to do with that genome is look at the genes that are present and absent, maybe try and work out what nutrients it is that it needs, so that we can supplement it and culture it in the laboratory and then characterise it fully. Syphilis is a disease that we’re very interested in. And it ranges from, initially, a very mild but well-known sexually-transmitted infection, to over the course of many years, becoming much progressively more serious and causing severe neurological disease. Over that period of time, it accumulates a number of SNPs. It also becomes less transmissible from patient to patient.
And we’re using direct sequencing without culture to study the accumulation of these SNPs, and how the organism evolves over time. And we hope this will give us insights into the way the disease works, and maybe how we can treat it going forwards. I work on cholera, which is caused by the bacterium Vibrio cholerae. People get cholera by ingesting contaminated food and water that have Vibrio cholerae within it. The WHO estimates that there are around 4 million cases per year with 150,000 deaths. So cholera is very alive and well at the moment. The current situation in the Yemen, where cholera cases are rapidly approaching one million, reminds us that cholera absolutely has a stronghold in the modern world.
And so what we’re trying to do with genomics is understand how cholera is moving across the globe. So historically, cholera epidemics have occurred in Africa and Latin America, and of course, in South Asia. But we didn’t really know how these epidemics, or if these epidemics were connected to one another. And what genomics has allowed us to do, is just absolutely link up the fact that epidemics within South Asia are connected to those in Africa, and are connected to those in Latin America.
And so through this, these high-resolution techniques, we’re able to have a much better understanding of how this disease is affecting millions of people a year, so that we can design better interventions and deploy vaccines in a much more efficient way. I’m working on bacterial persistence. Persistence is a phenotype in which a small fraction of a bacterial population survives through antibiotic treatment, even though the population is susceptible to antibiotics. And this leads to recurrent infections, because we’re unable to entirely eliminate bacterial populations under antibiotic treatment. And it’s a mechanism by which bacteria can acquire mobile genetic elements, like antimicrobial resistance genes, and become multi-drug resistant. Some genes have been known to be associated with persistence.
For example, toxin-antitoxin systems, in which the toxin inhibits the cells from growing. And that way they’re not affected by the antibiotics. I’m using genomics to develop a method to identify these genes that are known to be associated with persistence. And I’m going to try and use these genes to try and predict persistence under different conditions for different bacteria. For the last year, I’ve been working in the host- microbiota interactions lab. This lab looks at examining the population of the gut microbiome, which is the bacteria that live on and in the human body. We’re particularly interested in looking at how these affect health, and how we can use these to make sick people better.
My particular interests lie with looking at extra- chromosomal DNA, which are small pieces of DNA not contained in the main bacterial genome that bacteria used to communicate with one another. And these can be used in the future for genetic engineering of the gut microbiome. So I work on bacteria that live within your gut, and the antibiotic resistances that they can carry. So antibiotic resistance is a major problem. Obviously, antibiotics are a cornerstone of modern medicine. And yet, thousands of people die every year because of antibiotic-resistant infections. So this is really a problem that needs to be solved, and quickly.
So I use genomics to look at the antibiotic resistance genes that are carried by bacteria that live within your gut, and how they can pass within other bacteria that live in you and to any infectious bacteria that you may come into contact with. And we really hope that by using genomics to look into this, that we can start to prevent the spread of antibiotic resistance even further.

Learn more from six researchers who work here at the Wellcome Sanger Institute.

Susannah Salter is using genome sequencing to learn how a new species of bacteria could be grown in the lab, allowing it to be studied more easily.

Mathew Beale is sequencing genomes of the bacteria that cause syphilis to understand how it evolves within a single patient and becomes more harmful over time. He uses the term SNP in this video, which is an acronym for Single Nucleotide Polymorphism. These are single letter differences between genomes. These differences are commonly used for comparing closely related bacteria.

Daryl Domman uses genome sequencing to understand how cholera spreads across the globe.

Gal Horesh is interested in the genes that enable some bacteria to survive antibiotic treatment despite being susceptible to these drugs.

Tapoka Mkandawire studies genetic elements that can spread between bacteria and how these help to keep your gut healthy.

Lindsay Pike uses genome sequencing to study antibiotic resistance genes in good gut bacteria and how these can spread to infectious pathogens.

In the comments area, write which one of these research topics you are most interested in and give a reason for your choice? Link to areas that you are interested in, and share one or two links to good resources with a brief one sentence description.

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Bacterial Genomes: Disease Outbreaks and Antimicrobial Resistance

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