Spotlight on Grants: Eliminating plasmids for antibiotic resistance

Each year, the Microbiology Society awards a number of Research Visit Grants that enable our members to work in another laboratory anywhere in the world.

PhD student Alessandro Lazdins fom the University of Birmingham writes about his trip to Sydney earlier this year, to work on plasmids in mice.

In addition to their chromosomes, many bacteria contain plasmids – small, circular DNA molecules that typically carry advantageous genes, most notably those involved in antibiotic resistance. Plasmids are particularly problematic because they can be easily passed between different bacterial populations by a process called conjugation. This can rapidly spread antibiotic resistance genes in all sorts of environments, from sewage water to the guts of humans and animals.

As a PhD student at the Institute of Microbiology and Infection at the University of Birmingham, I have been studying whether we can eliminate these plasmids from their hosts. This would be particularly useful in clinical settings, where many infections are due to bacteria that are normally found in the guts of patients. If we could remove resistance plasmids from a patient’s gut before an infection develops, then treating that infection would become a lot easier.

Eliminating plasmids from a bacterium is known as ‘curing’. Put simply, our method, known as pCURE, uses specific plasmids that are able to block the replication of target plasmids without affecting their own. pCURE plasmids also neutralise the ‘self-destruct’ systems inside bacteria that cause them to die when they lose one of their own plasmids.

Up until now, pCURE has only been used as a lab method, but my project has developed a version that can spread between bacteria and shows very efficient curing. However, in order to take it closer to a possible clinical application, we wanted to know if we can displace plasmids that are present in the guts of mammals, initially mice.

In September 2016, I attended the biennial Plasmid Biology Conference in Cambridge, UK, where I met Professor Jon Iredell from the University of Sydney. Professor Iredell’s group has been working on a different plasmid curing idea and has tested it in mice. At the conference my supervisor discussed the possibility of me going to Sydney to test our pCURE in their mouse set-up. I applied for the Microbiology Society Research Visit Grant straight after the conference and, within four months, I had received the grant, organised visas, travel, accommodation, material transfer agreements and experimental procedures!

I arrived in sunny Sydney at the end of March this year, and spent the first 10 days preparing for the experiments and doing some sightseeing before the mice were delivered.

The experiment involved feeding the mice a sugary water solution containing E.coli bacteria that harboured my target plasmid. I then collected samples of their faeces and screened them to see if the bacteria had efficiently colonised the mouse gut. This step took longer than expected, requiring several adjustments to the protocol and a lot of mouse poo collection!

The pCURE plasmids that I was testing are conjugative, meaning that they can transfer from donor bacteria to recipient bacteria. I knew that if I managed to get our pCURE plasmid to transfer into the mouse E. coli, which carries the target plasmid, I would get curing.

So with that in mind, I fed the mice some E. coli carrying the pCURE plasmid and, after a couple hours, checked whether it had transferred to the bacteria in the mouse gut. Fortunately it had and I was able to show that when our pCURE plasmid gets into the target bacteria it will cure the antibiotic resistance plasmid.

Unfortunately this exciting result happened one day before my scheduled departure, but the group in Sydney will be able to build on the good preliminary data. Hopefully they can show that repeated exposure to pCURE plasmids will result in a full “decontamination” of antibiotic resistance plasmids from the mouse gut. In the longer term this result will allow the Birmingham group to apply for further funding for this technology.

The visit was a wonderful experience and I left having cemented an important collaboration. Visiting Australia was a fantastic opportunity not only to do a crucial part of my doctoral work, but also to experience different laboratory and work environments in a country I had never been to before. I am very grateful to the Microbiology Society for supporting me throughout my doctoral studies. –the conference grants and then this Research Visit Grant have truly allowed me to develop and grow as a scientist.

Alessandro Lazdins

To find out more about the Harry Smith Vacation Studentships, please contact grants@microbiologysociety.org

Image credit: Alessandro Lazdins
Posted in Clinical and Medical Microbiology, Grants | Tagged , , , | Leave a comment

What is a microbiome?

A microbiome is the community of micro-organisms living together in a particular habitat. Humans, animals and plants have their own unique microbiomes, but so do soils, oceans and even buildings. Watch our short animation to learn more.

Continue reading

Posted in Microbiome, Video | Leave a comment

Podcast: Annual Conference 2017 Roundup

Earlier this month, the Microbiology Society hosted our Annual Conference 2017 in Edinburgh. While we were there, we managed to catch up with just a few of the researchers presenting posters and giving talks.

Continue reading

Posted in Events, Podcast | Leave a comment

New to Science: Microbes from dogs, fish and ice cores

Each month, the Microbiology Society publishes the International Journal of Systematic and Evolutionary Microbiology (IJSEM), which details newly discovered species of bacteria, fungi and protists. Here are a few of the new species that have been discovered and the places they’ve been found. 

Spring is here. Well done everybody!

There’s a triptych of new Chryseobacterium species in our latest issue. C. cucumeris has been isolated from the root of a cucumber by a team from South Korea, while another group from the country has discovered C. nepalense in oil-contaminated soil. The final species, C. endophyticum, was isolated from a maize leaf by microbiologists from Taiwan. Continue reading

Posted in New to Science | Leave a comment

Annual Conference 2017 – a view from Twitter

The Microbiology Society’s Annual Conference 2017, which took place 3–6 April in Edinburgh, was our biggest event to date. After becoming fully booked weeks before it began, the four days saw over 1,800 delegates come through the doors and 600 posters on show – we managed to exceed our personal best that we set last year in Liverpool in 2016. Have a look at our Twitter summary of the best of this year’s Annual Conference. Continue reading

Posted in Events | 1 Comment

Investigating Lyme disease on the South Downs

The South Downs National Park is an area that stretches for 140 km along the South Coast of England, and is home to a huge diversity of plants and animals.

Some of the smaller inhabitants of the park are ticks: biting arachnids that feed on the blood of a wide range of mammals and birds, including deer, sheep and rodents. A number of these ticks are colonised by bacteria of the Borrelia genus, which are known to be the causative agent of Lyme disease, a potentially serious infection that can affect many parts of the body.

Last year, researchers from the University of Brighton suggested that the national park includes two of the ten areas in the UK where Lyme disease transmission is most common.

What the team weren’t able to show was why the park has high levels of transmission. Today, at the Microbiology Society’s Annual Conference, Dr Ian Cooper from the University of Brighton is presenting a poster explaining how the team are looking to answer that question. Continue reading

Posted in Animal Microbiology, Clinical and Medical Microbiology, Emerging Diseases | Tagged | 2 Comments

Pioneer fungi start degrading dead wood before it hits the ground

Next time you go walking in a forest during the summer months, take a look up and see if you can spot any branches missing their leaves. It might not seem obvious at first, but you’re looking at a poorly understood, although rather important, ecosystem.

As a tree grows, the branches nearest the base can become starved of light as the canopy spreads out above them, meaning that they use more energy than they create. Some types of tree actually ‘self prune’ these leafless branches, dropping them to the ground, where they get broken down by micro-organisms, returning their nutrients to the soil.

However, far from being dead weight, these limbs are actually vessels for numerous species of pioneer fungi that appear to be involved in the early decay process, while a branch remains attached to its tree. These fungi are able to break into parts of the wood that other fungi can’t reach, hastening the branch’s fall. Continue reading

Posted in Environmental Microbiology, Microbial Evolution and Diversity, Mycology | Leave a comment