Novel strategies for diagnosis and treatment of fungal infections

In vivo Immuno-Positron Emission Tomography/Magnetic Resonance Imaging of the fungal lung disease invasive pulmonary aspergillosis using the Aspergillus-specific monoclonal antibody JF5.

Studies led by Dr Steve Michell have identified a unique four-point test using easily measurable clinical variables which can be used to accurately predict the risk of death in patients with Clostridium difficile infection.

Microbes and Disease

Our research focus

The Microbes and Disease group focuses on understanding microbial systems, from the molecular and cellular level through to the population and community level, and defining the complex interactions between microbes and their hosts. Our research primarily focuses on bacterial and fungal pathogens of humans and animals, utilizing a range of methods including functional and comparative genomics, single-cell microfluidics, cellular and molecular biology, structural biology, population biology, mathematical modelling and molecular imaging. Working alongside industrial and clinical partners, the integration of these approaches enables us to address major global challenges associated with infectious diseases and the growing threat of antimicrobial resistance.

Research specialisms include:

  • emergence, evolution and epidemiology of infectious diseases;
  • evolution of virulence traits and antimicrobial resistance;
  • microbial physiology and its association with antimicrobial tolerance and virulence;
  • microbial signal transduction and stress adaptation;
  • microbial epitopes as candidates for vaccines and immunodiagnostics; and
  • molecular determinants of virulence and their role in shaping host-microbe interactions.

We have strong links with colleagues in the Fungal Biology and Plant Biology & Plant-Microbe Interactions research groups.

Recent research highlights

Extreme genome diversity in the most common eukaryotic pathogen of the human gut

An international team including Mark van der Giezen has sequenced the genome of the most common parasite found in the human intestines. Blastocystis has been linked to irritable bowel disease but can have a prevalence of up to 100% in certain populations, casting doubt on its overall virulence. Comparative analysis indicated an enormous genomic diversity of this parasite, similar to genomic differences normally associated with different species. This work clearly indicates the need for better diagnostics to understand the link between isolates and disease.

Gentekaki E et al. (2017) PLoS Biology 15(9): e2003769.

Tackling antimicrobial resistance head-on

Research led by Robert Beardmore and Ivana Gudelj is providing unique insight into the challenges associated with antimicrobial resistance. Recent studies have shed light on the molecular evolution of resistance and the associated trade-offs (Reding-Roman et al., 2017) and the efficacy of different antibiotic dosing regimens (Beardmore et al., 2017). Together, such studies aim to assess whether we can exploit knowledge of molecular evolution to slow the progression of antimicrobial resistance.

Reding-Roman C et al. (2017). Nat Ecol Evol. 1(3):50. | Read more here.

Beardmore RE et al. (2017). Mol Biol Evol. 34(4):802-817. | Read more here.

Breakthrough in understanding membrane pore insertion

Utilising electron cryo-microscopy, Rick Titball and collaborators at Birkbeck College and the MRC Laboratory of Molecular Biology have provided the first atomic resolution view of the pore structure of an aerolysin family pore-forming toxin, giving new insight into their mechanism of activation and membrane insertion.

Bokori-Brown M et al. (2016). Nat Commun. 7:11293.

Unravelling microbial strategies to subvert host responses to infection

Studies undertaken by Alan Brown in conjunction with collaborators at DSTL and University of Edinburgh have provided new insight into the pathogenesis of Burkholderia pseudomallei, the causative agent of melioidosis. The research team has identified secreted S1P lyase enzymes as critical virulence determinants, characterizing their kinetics and crystal structure (McLean et al., 2017) and their role in virulence (Custódio et al., 2016).

Custódio R et al. (2016). Mol Microbiol. 102(6):1004-1019.

McLean CJ et al. (2017). J Lipid Res. 58(1):137-150.

Novel strategies for diagnosis and treatment of fungal infections.

Christopher Thornton, working with a network of European collaborators, has 
developed a novel immunodiagnostic that allows the noninvasive diagnosis of 
invasive pulmonary aspergillosis, a life-threatening lung disease caused by Aspergillus fumigatus. This technology has enormous potential to transform the diagnosis and treatment of life-threatening fungal infections.

Rolle AM et al. (2016). Proc Natl Acad Sci USA. 113(8):E1026-33