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Identification of Rv1133c (MetE) as a marker of Mycobacterium tuberculosis replication and as a highly immunogenic antigen with potential immunodiagnostic power
The immunization of mice with the sterile culture medium supernatants of (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 Rv...
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Published in: | Frontiers in immunology 2024-10, Vol.15, p.1464923 |
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creator | Iacobino, Angelo Teloni, Raffaela Mancone, Carmine Facchiano, Francesco Di Giamberardino, Alessandra Senatore, Cinzia Di Virgilio, Antonio Lanni, Alessio Giannoni, Federico Nisini, Roberto Mariotti, Sabrina |
description | The immunization of mice with the sterile culture medium supernatants of
(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),
, or
. 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
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. |
doi_str_mv | 10.3389/fimmu.2024.1464923 |
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(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),
, or
. 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
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.</description><identifier>ISSN: 1664-3224</identifier><identifier>EISSN: 1664-3224</identifier><identifier>DOI: 10.3389/fimmu.2024.1464923</identifier><identifier>PMID: 39430745</identifier><language>eng</language><publisher>Switzerland: Frontiers Media S.A</publisher><subject>Animals ; Antibodies, Bacterial - immunology ; Antibodies, Monoclonal - immunology ; Antigens, Bacterial - immunology ; Bacterial Proteins - genetics ; Bacterial Proteins - immunology ; Biomarkers ; Humans ; Immunologic Tests - methods ; latent infection ; MetE ; Mice ; Mice, Inbred BALB C ; monoclonal antibodies ; Mycobacterium tuberculosis - immunology ; Rv1133c ; tuberculosis ; Tuberculosis - diagnosis ; Tuberculosis - immunology ; Tuberculosis - microbiology ; vitamin B12</subject><ispartof>Frontiers in immunology, 2024-10, Vol.15, p.1464923</ispartof><rights>Copyright © 2024 Iacobino, Teloni, Mancone, Facchiano, Di Giamberardino, Senatore, Di Virgilio, Lanni, Giannoni, Nisini and Mariotti.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c294t-d12bed46742035e822bf36af28578af5d4bcbf7b78595da54c148afb8aa173db3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39430745$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Iacobino, Angelo</creatorcontrib><creatorcontrib>Teloni, Raffaela</creatorcontrib><creatorcontrib>Mancone, Carmine</creatorcontrib><creatorcontrib>Facchiano, Francesco</creatorcontrib><creatorcontrib>Di Giamberardino, Alessandra</creatorcontrib><creatorcontrib>Senatore, Cinzia</creatorcontrib><creatorcontrib>Di Virgilio, Antonio</creatorcontrib><creatorcontrib>Lanni, Alessio</creatorcontrib><creatorcontrib>Giannoni, Federico</creatorcontrib><creatorcontrib>Nisini, Roberto</creatorcontrib><creatorcontrib>Mariotti, Sabrina</creatorcontrib><title>Identification of Rv1133c (MetE) as a marker of Mycobacterium tuberculosis replication and as a highly immunogenic antigen with potential immunodiagnostic power</title><title>Frontiers in immunology</title><addtitle>Front Immunol</addtitle><description>The immunization of mice with the sterile culture medium supernatants of
(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),
, or
. 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
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.</description><subject>Animals</subject><subject>Antibodies, Bacterial - immunology</subject><subject>Antibodies, Monoclonal - immunology</subject><subject>Antigens, Bacterial - immunology</subject><subject>Bacterial Proteins - genetics</subject><subject>Bacterial Proteins - immunology</subject><subject>Biomarkers</subject><subject>Humans</subject><subject>Immunologic Tests - methods</subject><subject>latent infection</subject><subject>MetE</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>monoclonal antibodies</subject><subject>Mycobacterium tuberculosis - immunology</subject><subject>Rv1133c</subject><subject>tuberculosis</subject><subject>Tuberculosis - diagnosis</subject><subject>Tuberculosis - immunology</subject><subject>Tuberculosis - microbiology</subject><subject>vitamin B12</subject><issn>1664-3224</issn><issn>1664-3224</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNpNUU1v1DAQjRCIVqV_gAPysRx2iT124hxRVWClVkgIztb4I7suSbzYTqv9N_xUnO62whePZt578-xXVe9pvQaQ3afej-O8ZjXja8ob3jF4VZ3TpuErYIy__q8-qy5Tuq_L4R0AiLfVGXQc6paL8-rvxrop-94bzD5MJPTkxwOlAIZc3bl885FgIkhGjL9dXKZ3BxM0muyin0eSZ-2imYeQfCLR7YdnHZzskbnz291wIIvbKWzd5E2ZZV8q8ujzjuxDXgzgcIJYj9sppFxw-_Do4rvqTY9Dcpen-6L69eXm5_W31e33r5vrz7crwzqeV5Yy7SxvWs5qEE4ypntosGdStBJ7Ybk2um91K0UnLApuKC99LRFpC1bDRbU56tqA92offXnyQQX06qkR4lZhLK4Gp8ofQt-gc8AoF20tBeNGWuAGRNMwLFpXR619DH9ml7IafTJuGHByYU4KKJUS2kIuUHaEmhhSiq5_WU1rtQStnoJWS9DqFHQhfTjpz3p09oXyHCv8A3ARpvc</recordid><startdate>20241004</startdate><enddate>20241004</enddate><creator>Iacobino, Angelo</creator><creator>Teloni, Raffaela</creator><creator>Mancone, Carmine</creator><creator>Facchiano, Francesco</creator><creator>Di Giamberardino, Alessandra</creator><creator>Senatore, Cinzia</creator><creator>Di Virgilio, Antonio</creator><creator>Lanni, Alessio</creator><creator>Giannoni, Federico</creator><creator>Nisini, Roberto</creator><creator>Mariotti, Sabrina</creator><general>Frontiers Media S.A</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>DOA</scope></search><sort><creationdate>20241004</creationdate><title>Identification of Rv1133c (MetE) as a marker of Mycobacterium tuberculosis replication and as a highly immunogenic antigen with potential immunodiagnostic power</title><author>Iacobino, Angelo ; Teloni, Raffaela ; Mancone, Carmine ; Facchiano, Francesco ; Di Giamberardino, Alessandra ; Senatore, Cinzia ; Di Virgilio, Antonio ; Lanni, Alessio ; Giannoni, Federico ; Nisini, Roberto ; Mariotti, Sabrina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c294t-d12bed46742035e822bf36af28578af5d4bcbf7b78595da54c148afb8aa173db3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animals</topic><topic>Antibodies, Bacterial - immunology</topic><topic>Antibodies, Monoclonal - immunology</topic><topic>Antigens, Bacterial - immunology</topic><topic>Bacterial Proteins - genetics</topic><topic>Bacterial Proteins - immunology</topic><topic>Biomarkers</topic><topic>Humans</topic><topic>Immunologic Tests - methods</topic><topic>latent infection</topic><topic>MetE</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>monoclonal antibodies</topic><topic>Mycobacterium tuberculosis - immunology</topic><topic>Rv1133c</topic><topic>tuberculosis</topic><topic>Tuberculosis - diagnosis</topic><topic>Tuberculosis - immunology</topic><topic>Tuberculosis - microbiology</topic><topic>vitamin B12</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Iacobino, Angelo</creatorcontrib><creatorcontrib>Teloni, Raffaela</creatorcontrib><creatorcontrib>Mancone, Carmine</creatorcontrib><creatorcontrib>Facchiano, Francesco</creatorcontrib><creatorcontrib>Di Giamberardino, Alessandra</creatorcontrib><creatorcontrib>Senatore, Cinzia</creatorcontrib><creatorcontrib>Di Virgilio, Antonio</creatorcontrib><creatorcontrib>Lanni, Alessio</creatorcontrib><creatorcontrib>Giannoni, Federico</creatorcontrib><creatorcontrib>Nisini, Roberto</creatorcontrib><creatorcontrib>Mariotti, Sabrina</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Frontiers in immunology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Iacobino, Angelo</au><au>Teloni, Raffaela</au><au>Mancone, Carmine</au><au>Facchiano, Francesco</au><au>Di Giamberardino, Alessandra</au><au>Senatore, Cinzia</au><au>Di Virgilio, Antonio</au><au>Lanni, Alessio</au><au>Giannoni, Federico</au><au>Nisini, Roberto</au><au>Mariotti, Sabrina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Identification of Rv1133c (MetE) as a marker of Mycobacterium tuberculosis replication and as a highly immunogenic antigen with potential immunodiagnostic power</atitle><jtitle>Frontiers in immunology</jtitle><addtitle>Front Immunol</addtitle><date>2024-10-04</date><risdate>2024</risdate><volume>15</volume><spage>1464923</spage><pages>1464923-</pages><issn>1664-3224</issn><eissn>1664-3224</eissn><abstract>The immunization of mice with the sterile culture medium supernatants of
(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),
, or
. 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
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.</abstract><cop>Switzerland</cop><pub>Frontiers Media S.A</pub><pmid>39430745</pmid><doi>10.3389/fimmu.2024.1464923</doi><oa>free_for_read</oa></addata></record> |
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subjects | Animals Antibodies, Bacterial - immunology Antibodies, Monoclonal - immunology Antigens, Bacterial - immunology Bacterial Proteins - genetics Bacterial Proteins - immunology Biomarkers Humans Immunologic Tests - methods latent infection MetE Mice Mice, Inbred BALB C monoclonal antibodies Mycobacterium tuberculosis - immunology Rv1133c tuberculosis Tuberculosis - diagnosis Tuberculosis - immunology Tuberculosis - microbiology vitamin B12 |
title | Identification of Rv1133c (MetE) as a marker of Mycobacterium tuberculosis replication and as a highly immunogenic antigen with potential immunodiagnostic power |
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