Institute of Infection

 

AMR occurs naturally over time, usually through genetic changes. Antimicrobial resistant organisms are found in people, animals, food, plants and the environment (water, soil and air). They can spread from person to person or between people and animals. However, the main drivers of antimicrobial resistance is the misuse and overuse of antimicrobials. This can be caused by poor access to quality, affordable medicines, vaccines and diagnostics, amongst other factors, but is also a consequence of clinicians often not having sufficient information to prescribe the most appropriate course of treatment. For example, it is currently difficult for clinicians to know at the point of diagnosis whether an infection is bacterial or viral: knowing even this level of detail would inform whether antibiotics are appropriate for treatment (for a bacterial infection) or not (for a viral infection) In fact, any technology that can provide information on the pathogen and its level of resistance, information on the host immune system, or the dosing required for individual patients, will be vital in preventing misuse and overuse. This is why diagnostics are such a critical component of our fight against AMR. This requires advances in innovation and increased investment into them.  –   

In our third blog of our AMR series, the Institute of Infection speaks to Dr Gerald Larrouy-Maumus (Department of Life Science) and Dr Jesus Rodriguez Manzano (Department of Infectious Disease) about diagnostics. Dr Larrouy-Maumus’s laboratory is focused on infectious diseases, especially human tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), which is one of mankind’s most successful intracellular pathogens. He aims to determine how Mtb is able to survive within the host cell using the state-of-the-art mass spectrometry instruments available in his laboratory. Dr Jesus Rodriguez Manzano’s group are developing and implementing innovative methods for molecular diagnosis of infectious diseases and AMR. He is working towards transforming the field of medicine by facilitating diagnosis across different environments, to improve clinical outcomes, reduce unnecessary antimicrobial prescribing and help address the challenges of antimicrobial resistance.  

In addition to the work below, we encourage you to check out other diagnostics research programmes at Imperial (including the NIHR Global Health Research Group on Digital Diagnostics for African Health Systems, the DIAMONDS project, and the B2B2B AMRDx network) as well as the centres and networks that have diagnostics for AMR element: the Centre for Antimicrobial Optimisation, the Centre for Bacterial Resistance Biology (CBRB), the NIHR Health Protection Research Unit (NIHR HPRU) in Healthcare Associated Infections and Antimicrobial Resistance, and the Imperial College Academic Health Science Centre. 

Tell me about yourself and your research  

GLM: I joined Imperial’s Department of Life Science in 2014 as Lecturer, being promoted to Reader in 2023. Since then, I have enjoyed every day of my career there. Being at Imperial surrounded by talented and enthusiastic colleagues, support staff and students is a real privilege and intellectually stimulating. This allow me to be outside my comfort zone daily and be able to contribute to the tackling of  big challenge such as AMR while training the next generation of scientists.  

Over the last years, at the Centre for Bacterial Resistance Biology, my laboratory has developed cutting edge expertise in biochemistry, lipidomics and metabolomics of bacterial pathogens. The major aim of my laboratory is to understand how mycobacterial metabolic flexibility impacts drug resistance and immune persistence. We study mainly the pathogen Mycobacterium tuberculosis, which remains one of the top killers worldwide with over 1.5 million death per year. By being able to understand how the pathogen can adapt and cope to host environmental cues and by interfering with this process, we hope to provide new route to develop new and shorter treatments.  

My lab is also pioneering bacterial antibiotics susceptibility testing on intact bacteria using lipids for identification and read-out of AMR using routine MALDI-ToF, the workhorse of clinical microbiology labs worldwide. That work led, in 2022, to the commercialisation of a kit named MBT Lipid Xtract™ Kit (RUO, Bruker) that allows the rapid detection, within 30 mins of bacteria resistance to last-resort antibiotics, a process that used to take 2 to 3 days. 

JRM: I am a molecular biologist by training. Currently, I hold a Senior Lecturer position at Imperial within the Department of Infectious Disease and am part of the NIHR HPRU in Healthcare Associated Infections and Antimicrobial Resistance. In addition, I serve as the Deputy Director for the Centre for Antimicrobial Optimisation (CAMO) and I am a co-founder and Chief Scientific Officer at ProtonDx. 

I am passionate about merging science and technology to create new diagnostic capabilities and technologies for infectious diseases and AMR.  My aim is to improve patient management and clinical outcomes and to reduce unnecessary antimicrobial prescribing.  

My current research focuses on three key areas: 

  

1. Development and translation of sample-to-result molecular-based diagnostic devices for point-of-care applications, facilitating the establishment of decentralized healthcare systems. 
2. Utilization of machine learning approaches in conjunction with PCR-based amplification chemistries to enable accurate high-level multiplexing in both conventional real-time instruments and state-of-the-art digital PCR platforms. This enhances the throughput of diagnostic laboratories without the need for hardware modification. 
3. Development and validation of a novel framework for biomarker discovery to optimize the translation of host-response signatures from high-throughput platforms (e.g., RNAseq) to PCR-based and point-of-care technologies. 

What are the key challenges in your research area?   

GLM: Undoubtedly, the key challenges are to attract funding and translate the research from the bench to the bed. Investment to tackle TB and more broadly AMR must be drastically inspired by the ones that were allocated to COVID-19 if we want to win the race against the hidden pandemic that is AMR globally.  

JRM: The integration of novel diagnostic approaches into healthcare systems and at the point-of-care is a critical challenge, as it requires overcoming logistical, infrastructural, and regulatory hurdles to ensure widespread adoption. The input from clinical colleagues and other practitioners who will use my diagnostic tools, including healthcare professionals and veterinarians, is essential in overcoming these challenges. I am fortunate to work in an environment that encourages and values the input of a diverse range of professions and disciplines. 

 

Where do you see your research going in 5 years’ time?   

GLM: In the near future, we aim to maximise our impact by providing new diagnostics solutions to the current clinical unmet needs in the field of AMR and providing innovative route to tackle tuberculosis. To this aim, we have recently identified critical metabolic pathways that can definitively be targeted to reduce the burden of persistent TB, which could lead to shorten drug regimen.  

JRM: Overall, my overarching goal is to translate these research developments into tangible improvements in patient management and clinical outcomes in the NHS and in other healthcare settings. I see my work playing a crucial role in revolutionising diagnostic capabilities of infectious diseases and AMR, ultimately contributing to more efficient and personalized healthcare practices. 

 

What do you perceive as the “origins” of antimicrobial resistance?   

GLM: We have to keep in mind that AMR is a natural process and that microorganisms were developing resistance prior to the discovery of penicillin by Sir Alexander Fleming back in 1928 at St Mary’s campus. The misuse and overuse of antimicrobials over the last 80 years have led to an uncontrolled raised of superbugs globally. That is why, alongside new and innovative approaches to target those superbugs, affordable, easy to use and deployed globally diagnostics approached can be a game changer to rapidly provide the appropriate drug regimen and stop “shooting in the dark”.   

JRM: The origin of AMR is intrinsically tied to the use of antimicrobials, rooted in the fundamental principle of natural selection. Nevertheless, the implementation of rigorous antimicrobial stewardship programs, promotion of responsible antibiotic use, and enhancement of diagnostic and surveillance systems to monitor AMR have the potential to mitigate this global issue. 

 

Where do you think Imperial’s strengths lie in this field?   

GLM: Imperial has considerable talent and interdisciplinary research to lead the race against AMR. With world-expert academics focused on molecular mechanisms of AMR at the CBRBto clinicians via cross-disciplinary Institutes, Imperial has the key to being a major player in tackling AMR.    

JRM: Imperial provides an ideal environment for interdisciplinary and translational research, fostering innovation and entrepreneurship. Based on my personal experience, we undoubtedly rank among the top research institutions in this area. The interaction with clinical staff through co-location and joint projects is invaluable. 

What solutions would you like to see in the future?   

GLM: In the future, public engagement along with constant support from funders and policy makers can play a crucial role to generate innovative solutions, train the next generation of scientist and provide a proportionate use of antimicrobials.  

JRM: Within the scope of diagnostics for AMR, I envision affordable and accessible technologies for both genotypic and phenotypic testing methods that can be deployed in resource-limited settings, promoting widespread adoption. Additionally, I would like to see the establishment of global surveillance networks that systematically collect and analyse data to inform diagnostic development, and flexible regulatory pathways capable of accommodating out-of-the-box and disruptive diagnostic solutions. 

How important is an interdisciplinary approach to AMR research?   

GLM: Interdisciplinary research is not only important but the cornerstone of tacking AMR globally. We absolutely need everyone involved to address one of this century’s challenges. 

JRM: It is crucial because AMR is a complex and multifaceted issue that extends beyond the realms of microbiology and medicine. Looking specifically at the diagnostic angle, AMR research involves collaboration between molecular biologists, clinicians, microbiologists, engineers, data scientists, and healthcare policymakers. 

Are you optimistic that we can successfully overcome the challenges posed by AMR? 

GLM: Even though academic research is at the forefront of AMR research, we still have a long way to go before successfully overcoming the challenges posed by AMR. We must pull all in the same direction as we did brilliantly for COVID-19. The silent pandemic posed by AMR can be considered worse that COVID-19 in terms of death and global economy. If nothing is done urgently, even someone with a simple cold due to a bacterial infection can die. We, academics, along with funders, the public, and industry, seriously need to roll up our sleeves and get down to the problem now before it is too late. 

JRM: I believe that by collaborating globally, sustaining research efforts, and implementing public health measures, we can overcome most of the challenges presented by AMR. However, AMR is not an issue that science and technology alone can address. Increased public understanding of AMR is crucial as well. This is to ensure the appropriate use of antimicrobials and the adoption of other important infection prevention behaviours. 

In March 2023, as part of our ‘Meet 7 Researchers working to end TB’ Imperial story we spoke to Ivana Pennisi from Dr Rodriguez-Manzano and Professor Georgiou’s interdisciplinary research groups in the Department of Electrical and Electronic Engineering. She described the new TB diagnostic devices that she’s helping to create.  

Click here to read her extract