Tag Archives: antimicrobial resistance

Spanner in the works for a parasite motor

Throughout World Antimicrobial Awareness Week, we’re featuring key areas of research at Birkbeck relating to the management of diseases. In this blog, we feature the work of former PhD student, Alex Cook, who is looking at new approaches to malaria control.

Alex Cook

Alex Cook

Separated by 85 million years of evolution, the parasite Plasmodium falciparum that causes the most deadly form of malaria, is a very different beast to its human host. Yet the challenge for malaria treatments is that they must kill the parasite but not destroy the cells of their human host in which the parasite hides. Malaria is a massive disease burden world-wide. Hundreds of thousands of people are killed each year, the majority of which are children younger than five. In Africa, disruption arising from the COVID-19 pandemic to existing measures also threatens to undo the last decade of malaria control. With resistance to current frontline therapeutics rapidly rising, new drug targets and vaccines are urgently needed.

Malaria-causing parasites are single cells and have a complex life-cycle within both human and mosquito hosts. The many iterations of parasite proliferation that are essential for disease transmission are driven by intracellular machinery called the mitotic spindle, which is built of cytoskeleton components called microtubules. This machinery ensures the correct distribution of replicated chromosomes to the newly produced cells. Targeting of the mitotic spindle by drugs is well-established in a variety of settings – notably human cancers – and components of the malaria proliferative machinery are thus attractive anti-parasite targets.

As part of his PhD work in the research group of Professor Carolyn Moores (Biological Sciences), Alex Cook studied a component of the malaria mitotic spindle machinery, a molecular motor called kinesin-5. Kinesin-5’s are a family of proteins known for their ability to ‘push and pull’ microtubules to create ordered structures within the cell. Alex used a very powerful electron microscope to take images of kinesin-5 molecules – which are around a millionth of a millimetre in size – bound to individual microtubules. He then used computational analysis to combine these pictures and calculate their three-dimensional shape, thereby providing information about how the motors work in the parasite themselves.

the Kinesin protein that contributes to malaria

Using this information, Alex – who is co-supervised by Professor Maya Topf and also collaborates with Dr Anthony Roberts, both also in Biological Sciences – showed that although the malaria kinesin-5 motor shares some functional properties with human kinesin-5, there are several key differences that indicate it might be susceptible to specific drug targeting. Confirming this idea, Alex found that a drug-like molecule that blocks human kinesin-5 activity does not affect the parasite motor.

Alex Cook, who is now a postdoctoral researcher at the University of Oxford said: “To uncover new approaches to malaria control, we urgently need to look at new molecules from the parasite. Using high resolution electron microscopy, this first look at a parasite cell division motor will provide a springboard for discovery of small molecules that can disrupt malaria replication.”

Professor Moores commented: “Alex’s hard work, together with vital support from our department’s lab and computational teams, demonstrates the power of electron microscopy to explore medically important challenges.”

Alex’s work was recently published in The Journal of Biological Chemistry (https://doi.org/10.1016/j.jbc.2021.101063). Future directions for the project involve further investigation of specific motor inhibitors, and also of the function of kinesin-5 in the parasite itself, in collaboration with the research group of Professor Rita Tewari at the University of Nottingham.

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Abusing Antibiotics: The Unknown Phenomenon

This week, 18 to 24 November, marks World Antimicrobial Awareness Week, and this year’s theme is ‘Spread Awareness, Stop Resistance’. In this blog, Professor Sanjib Bhakta, Professor of Molecular Microbiology and Biochemistry, discusses the effect of the COVID-19 pandemic on antimicrobial resistance, why this is so alarming, and how research at Birkbeck is making a difference.

Headshot of Professor Sanjib Bhakta

Professor Sanjib Bhakta

Antimicrobial resistance (AMR) is an alarming global crisis which inevitably arose alongside the ground-breaking discovery of antibiotics and its subsequent use to save billions of human and animal lives. The ongoing COVID-19 pandemic has caused a redirection of resources worldwide to fight the coronavirus. Naturally, this has meant resources such as Global Challenges Research Fund (GCRF) to fight antibiotic resistance have been disrupted.

COVID-19 has affected AMR rates and research dramatically in the last 18 months. There have been changes in availability of staff to research, treat and screen for AMR pathogens (disease-causing germs) leading to under-reporting of AMR cases. There has also been an increase of broad-spectrum antibiotic prescription, at least in some parts of the world due to possible bacterial co-infection and clinical presentation of cases, which has led to increased selection pressure on pathogens. As well as this, the introduction of disinfectant overuse could be driving mutation and increasing AMR rates. Despite reduced exposure due to COVID-19 measures, other factors have meant that AMR rates have increased. In order to stop this rise, better stewardship for antibiotic use need to be implemented.

Tackling the rise of antimicrobial resistance is central to our multidisciplinary research at the Institute of Structural and Molecular Biology (ISMB) Mycobacteria Research Laboratory and for our national and international collaborative partners. We investigate metabolism in order to address antimicrobial drug resistance in tuberculosis (TB); tackling this challenge by discovering novel antibiotic-leads and repurposing over-the-counter painkillers to cure TB and other non-tubercular mycobacterial (NTM) infections.

We have paid special attention to the study of the cell-walls of World Health Organisation (WHO)-priority bacteria in an ongoing ASEM-DUO fellowship exchange programme between the Indian Institute of Technology – India and Birkbeck, University of London, as cell-walls are an important site for attack by antibiotics such as penicillin. This inter-institutional collaboration between the UK and India continues to build a strong international research programme to tackle AMR and accelerate the development of new and effective treatment options.

Parallel to our lab-based research endeavours, we have integrated interdisciplinary approaches to tackle antimicrobial drug resistance in superbugs in partnership with ‘Joi Hok’, a community TB awareness programme in West Bengal, India. In this award-winning Microbiology Society Outreach Prize project, we have raised awareness of TB and antibiotic resistance with school children, their families, and local communities, through traditional storytelling, folk art, painting, and music.

To mark World Antimicrobial Awareness Week 2021 at Birkbeck, we have organised a student-led public-awareness presentation, an international students’ experience event and a research webinar series where we will be brainstorming the significance of interdisciplinary initiatives and strategies to tackle AMR.

If the current trend continues, there will be more than 10 million preventable deaths every year by 2050. Therefore, we must take every possible measure against antibiotic resistance in infectious diseases, now rather than later, before this major global health challenge goes beyond our capacity to control.

Further information