Engineered Mycobacterium tuberculosis antigen assembly into core-shell nanobeads for diagnosis of tuberculosis

Sheffee NS 1 , Rubio-Reyes P 2 , Mirabal M 3 , Calero R 4 , Carrillo-Calvet H 5 , Chen S 6 Show all authors , Chin KL 7 , Shakimi NAS 1 , Anis FZ 1 , Suraiya S 8 , Sarmiento ME 9 , Norazmi MN 10 , Acosta A 11 , Rehm BHA 12

Affiliations 

  • 1 School of Health Sciences, Universiti Sains Malaysia (USM), Kubang Kerian, Kelantan, Malaysia
  • 2 Institute of Fundamental Sciences, Massey University, Private Bag 11222, Palmerston North, New Zealand
  • 3 Centre for Complexity Sciences, National Autonomous University of Mexico (UNAM), Mexico; Institute of Nuclear Sciences, National Autonomous University of Mexico (UNAM), Mexico
  • 4 Centre for Complexity Sciences, National Autonomous University of Mexico (UNAM), Mexico
  • 5 Centre for Complexity Sciences, National Autonomous University of Mexico (UNAM), Mexico; Faculty of Sciences, National Autonomous University of Mexico (UNAM), Mexico
  • 6 Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD, 4111, Menzies Health Institute Queensland, Griffith University (Gold Coast Campus), Australia
  • 7 Department of Biomedical Sciences and Therapeutic, Faculty of Medicine and Health Sciences (FPSK), Universiti Malaysia Sabah (UMS), Sabah, Malaysia
  • 8 Medical Microbiology Department, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia
  • 9 School of Health Sciences, Universiti Sains Malaysia (USM), Kubang Kerian, Kelantan, Malaysia. Electronic address: [email protected]
  • 10 School of Health Sciences, Universiti Sains Malaysia (USM), Kubang Kerian, Kelantan, Malaysia. Electronic address: [email protected]
  • 11 School of Health Sciences, Universiti Sains Malaysia (USM), Kubang Kerian, Kelantan, Malaysia. Electronic address: [email protected]
  • 12 Centre for Cell Factories and Biopolymers, Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD, 4111, Menzies Health Institute Queensland, Griffith University (Gold Coast Campus), Australia. Electronic address: [email protected]
Nanomedicine, 2021 06;34:102374.
PMID: 33675981 DOI: 10.1016/j.nano.2021.102374

Abstract

Despite recent advances in diagnosis, tuberculosis (TB) remains one of the ten leading causes of death worldwide. Here, we engineered Mycobacterium tuberculosis (Mtb) proteins (ESAT6, CFP10, and MTB7.7) to self-assemble into core-shell nanobeads for enhanced TB diagnosis. Respective purified Mtb antigen-coated polyester beads were characterized and their functionality in TB diagnosis was tested in whole blood cytokine release assays. Sensitivity and specificity were studied in 11 pulmonary TB patients (PTB) and 26 healthy individuals composed of 14 Tuberculin Skin Test negative (TSTn) and 12 TST positive (TSTp). The production of 6 cytokines was determined (IFNγ, IP10, IL2, TNFα, CCL3, and CCL11). To differentiate PTB from healthy individuals (TSTp + TSTn), the best individual cytokines were IL2 and CCL11 (>80% sensitivity and specificity) and the best combination was IP10 + IL2 (>90% sensitivity and specificity). We describe an innovative approach using full-length antigens attached to biopolyester nanobeads enabling sensitive and specific detection of human TB.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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