A Step Towards Rapid Early Detection of Chagas Disease

American trypanosomiasis, or Chagas disease, is an NTD that affects between six and seven million people worldwide. The disease is primarily caused by a parasite (Trypanosoma cruzi) and was initially confined to rural areas of Latin America. However, population changes mean that most infected people now live in urban areas. And as Chagas can be transmitted between infected people (via blood transfusions and transplants and from mothers to unborn children), it is increasingly found on other continents. There is no vaccine for Chagas disease, and up to 30% of chronically infected people develop heart problems, with up to 10% developing digestive or neurological issues. In addition, the drugs currently approved for treating CD require long treatment durations and have several side effects, including drug toxicity.

CD can be diagnosed using parasitological tests in its early, acute phase and by detecting the α-T. cruzi IgG antibodies in the later chronic stage by. However, containing the spread of CD is challenging because the infection is asymptomatic in its early stages. As we have seen with COVID-19, the development of rapid, highly sensitive diagnostic tests is essential to control the spread of infectious diseases and to understand their epidemiology.

In work recently published in Vaccines, researchers used high-resolution X-ray diffraction on Diamond's I04 Microfocus Macromolecular Crystallography (MX) beamline to solve the structure of a surface membrane protein from T. cruzi (TcSMP). TcSMP is highly conserved among different Trypanosoma species, which makes it an ideal candidate for CD diagnosis. Their detailed analysis of the solved TcSMP crystal structure is only the second of its kind deposited in the publically accessible Protein Data Bank archive (PDB).

In this pilot study, the researchers demonstrated the ability of recombinant TcSMP to detect antibodies from CD infected subjects, confirming its potential as a diagnostic biomarker. 

Using the crystal structure and a structure-based computational method, they revealed a particularly immunogenic region of the protein. Further work is needed to develop an effective diagnostic test, but these results bring us a step closer.

This work was carried out by a team of researchers from institutions across Italy. Their access to Diamond was facilitated by iNEXT, an EU scheme providing a single point of entry for transnational user access to synchrotrons, nuclear magnetic resonance facilities and electron microscopes. Following its success, this scheme has now been superseded by iNEXT-Discovery, which brings together structural biology facilities for X-rays, NMR, cryo-EM and macromolecular biophysics. The partnership aims to make these facilities accessible to new user communities, to develop the methods further through joined research efforts, and to offer better integration between scientific fields and within the field of structural biology through scientific meetings, practical courses, and training workshops.

At Diamond, iNEXT Discovery provides access to:

• Fragment screening campaigns (beamline I04-1)
• MX (serial, nanocrystallography, and long wavelength) experiments (beamlines I24, VMXi, VMXm, I23)
• BioSAXS (mail-in only) (beamline B21)
• Cryo-EM (single particle and cryo-electron tomography, with FIB milling for sample preparation) (eBIC)
• Cryo soft x-ray tomography (cryo-SXT) experiments (beamline B24) 

Users receive expert assistance in the operation of specialised equipment, with local support available 24/7. Laboratories, room for sample preparation and office space are also available.

To find out more about the I04 beamline or discuss potential applications, please contact Principal Beamline Scientist Ralf Flaig: ralf.flaig@diamond.ac.uk