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

被引:0
|
作者
Iacobino, Angelo [1 ]
Teloni, Raffaela [1 ]
Mancone, Carmine [2 ]
Facchiano, Francesco [3 ]
Di Giamberardino, Alessandra [2 ]
Senatore, Cinzia [3 ]
Di Virgilio, Antonio [4 ]
Lanni, Alessio [1 ]
Giannoni, Federico [1 ]
Nisini, Roberto [1 ]
Mariotti, Sabrina [1 ]
机构
[1] Ist Super Sanita, Dipartimento Malattie Infett, Rome, Italy
[2] Sapienza Univ Roma, Dipartimento Med Mol, Rome, Italy
[3] Ist Super Sanita, Dipartimento Oncol & Med Mol, Rome, Italy
[4] Ist Super Sanita, Ctr Sperimentaz Benessere Anim, Rome, Italy
来源
FRONTIERS IN IMMUNOLOGY | 2024年 / 15卷
关键词
tuberculosis; latent infection; vitamin B12; monoclonal antibodies; MetE; Rv1133c; diagnosis; METHIONINE SYNTHASE METE; ANTIBODIES; EXPRESSION; MODEL;
D O I
10.3389/fimmu.2024.1464923
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 an 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 Escherichia coli. Taking advantage of our mAbs, we studied (i) the vitamin B12 dependence 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, which are assumed to be 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.
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页数:12
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