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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Microbial Immunology
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1464923

Identification of Rv1133c (MetE) as a marker of Mycobacterium tuberculosis replication and as a highly immunogenic antigen with potential immunodiagnostic power

Provisionally accepted
Angelo Iacobino Angelo Iacobino 1Raffaela Teloni Raffaela Teloni 1Carmine Mancone Carmine Mancone 2Francesco Facchiano Francesco Facchiano 3Alessandra D. Giamberardino Alessandra D. Giamberardino 2Cinzia Senatore Cinzia Senatore 3Antonio Di Antonio Di 4Alessio Lanni Alessio Lanni 1Federico Giannoni Federico Giannoni 1Roberto Nisini Roberto Nisini 1*Sabrina Mariotti Sabrina Mariotti 1
  • 1 Dipartimento di Malattie Infettive, National Institute of Health (ISS), Rome, Italy
  • 2 Sapienza University of Rome, Rome, Lazio, Italy
  • 3 Dipartimento Oncologia e Medicina Molecolare, National Institute of Health (ISS), Rome, Lazio, Italy
  • 4 Centro per la Sperimentazione ed il Benessere Animale, National Institute of Health (ISS), Rome, Italy

The final, formatted version of the article will be published soon.

    The immunization of mice with the sterile culture medium supernatants of Mycobacterium tuberculosis (Mtb) H37Rv permitted the production of several monoclonal antibodies (mAbs) specific for secreted and/or released antigens. Two mAbs bound and immunoprecipitated an 80 kDa protein that was identified by mass spectrometry as Rv1133c, the methionine synthase MetE. The protein MetE is ubiquitous among prokaryota and shows a significant sequence homology in many bacteria. We produced both the full-length recombinant MetE and its N-terminal fragment, whose sequence is more conserved among mycobacteria, to select mAbs recognizing a Mtb specific region of MetE. Finally, we produced and selected eight mAbs that specifically detect the MetE protein in the supernatant and cell lysate of Mtb and BCG, but not other bacteria such as non-tuberculous mycobacteria (NTM), Streptococcus pneumoniae, Staphylococcus aureus, Acinetobacter baumanii or E. coli. Taking advantage of our mAbs, we studied i) the vitamin B12 dependance for the synthesis of MetE in Mtb and NTM and ii) the kinetics of MetE production and secretion in supernatants during the in vitro reproduced replicative, dormant and resuscitation cycle of Mtb. Our data demonstrate that dormant Mtb, that are assumed prevalent in latent infections, as well as NTM do not produce and secrete MetE. Results indicate an unexpected specificity for Mtb of our anti-MetE mAbs and encourage the use of rMetE and our mAbs as tools for the immunodiagnosis of TB and its stages.

    Keywords: Tuberculosis, latent infection, Vitamin B12, monoclonal antibodies, metE, Rv1133c, diagnosis

    Received: 15 Jul 2024; Accepted: 11 Sep 2024.

    Copyright: © 2024 Iacobino, Teloni, Mancone, Facchiano, Giamberardino, Senatore, Di, Lanni, Giannoni, Nisini and Mariotti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Roberto Nisini, Dipartimento di Malattie Infettive, National Institute of Health (ISS), Rome, 00161, Italy

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