Identification of Mycobacterium tuberculosis Peptides in Serum Extracellular Vesicles from Persons with Latent Tuberculosis Infection
Identification of biomarkers for latent infection and risk of progression to tuberculosis (TB) disease are needed to better identify individuals to target for preventive therapy, predict disease risk, and potentially predict preventive therapy efficacy. Our group developed multiple reaction monitori...
Gespeichert in:
| Veröffentlicht in: | Journal of clinical microbiology Jg. 58; H. 6 |
|---|---|
| Hauptverfasser: | , , , , , , , , |
| Format: | Journal Article |
| Sprache: | Englisch |
| Veröffentlicht: |
United States
26.05.2020
|
| Schlagworte: | |
| ISSN: | 1098-660X, 1098-660X |
| Online-Zugang: | Weitere Angaben |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Abstract | Identification of biomarkers for latent
infection and risk of progression to tuberculosis (TB) disease are needed to better identify individuals to target for preventive therapy, predict disease risk, and potentially predict preventive therapy efficacy. Our group developed multiple reaction monitoring mass spectrometry (MRM-MS) assays that detected
peptides in serum extracellular vesicles from TB patients. We subsequently optimized this MRM-MS assay to selectively identify 40
peptides from 19 proteins that most commonly copurify with serum vesicles of patients with TB. Here, we used this technology to evaluate if
peptides can also be detected in individuals with latent TB infection (LTBI). Serum extracellular vesicles from 74 individuals presumed to have latent
infection (LTBI) based on close contact with a household member with TB or a recent tuberculin skin test (TST) conversion were included in this study. Twenty-nine samples from individuals with no evidence of TB infection by TST and no known exposure to TB were used as controls to establish a threshold to account for nonspecific/background signal. We identified at least one of the 40
peptides in 70 (95%) individuals with LTBI. A single peptide from the glutamine synthetase (GlnA1) enzyme was identified in 61/74 (82%) individuals with LTBI, suggesting peptides from
proteins involved in nitrogen metabolism might be candidates for pathogen-specific biomarkers for detection of LTBI. The detection of
peptides in serum extracellular vesicles from persons with LTBI represents a potential advance in the diagnosis of LTBI. |
|---|---|
| AbstractList | Identification of biomarkers for latent
infection and risk of progression to tuberculosis (TB) disease are needed to better identify individuals to target for preventive therapy, predict disease risk, and potentially predict preventive therapy efficacy. Our group developed multiple reaction monitoring mass spectrometry (MRM-MS) assays that detected
peptides in serum extracellular vesicles from TB patients. We subsequently optimized this MRM-MS assay to selectively identify 40
peptides from 19 proteins that most commonly copurify with serum vesicles of patients with TB. Here, we used this technology to evaluate if
peptides can also be detected in individuals with latent TB infection (LTBI). Serum extracellular vesicles from 74 individuals presumed to have latent
infection (LTBI) based on close contact with a household member with TB or a recent tuberculin skin test (TST) conversion were included in this study. Twenty-nine samples from individuals with no evidence of TB infection by TST and no known exposure to TB were used as controls to establish a threshold to account for nonspecific/background signal. We identified at least one of the 40
peptides in 70 (95%) individuals with LTBI. A single peptide from the glutamine synthetase (GlnA1) enzyme was identified in 61/74 (82%) individuals with LTBI, suggesting peptides from
proteins involved in nitrogen metabolism might be candidates for pathogen-specific biomarkers for detection of LTBI. The detection of
peptides in serum extracellular vesicles from persons with LTBI represents a potential advance in the diagnosis of LTBI. Identification of biomarkers for latent Mycobacterium tuberculosis infection and risk of progression to tuberculosis (TB) disease are needed to better identify individuals to target for preventive therapy, predict disease risk, and potentially predict preventive therapy efficacy. Our group developed multiple reaction monitoring mass spectrometry (MRM-MS) assays that detected M. tuberculosis peptides in serum extracellular vesicles from TB patients. We subsequently optimized this MRM-MS assay to selectively identify 40 M. tuberculosis peptides from 19 proteins that most commonly copurify with serum vesicles of patients with TB. Here, we used this technology to evaluate if M. tuberculosis peptides can also be detected in individuals with latent TB infection (LTBI). Serum extracellular vesicles from 74 individuals presumed to have latent M. tuberculosis infection (LTBI) based on close contact with a household member with TB or a recent tuberculin skin test (TST) conversion were included in this study. Twenty-nine samples from individuals with no evidence of TB infection by TST and no known exposure to TB were used as controls to establish a threshold to account for nonspecific/background signal. We identified at least one of the 40 M. tuberculosis peptides in 70 (95%) individuals with LTBI. A single peptide from the glutamine synthetase (GlnA1) enzyme was identified in 61/74 (82%) individuals with LTBI, suggesting peptides from M. tuberculosis proteins involved in nitrogen metabolism might be candidates for pathogen-specific biomarkers for detection of LTBI. The detection of M. tuberculosis peptides in serum extracellular vesicles from persons with LTBI represents a potential advance in the diagnosis of LTBI.Identification of biomarkers for latent Mycobacterium tuberculosis infection and risk of progression to tuberculosis (TB) disease are needed to better identify individuals to target for preventive therapy, predict disease risk, and potentially predict preventive therapy efficacy. Our group developed multiple reaction monitoring mass spectrometry (MRM-MS) assays that detected M. tuberculosis peptides in serum extracellular vesicles from TB patients. We subsequently optimized this MRM-MS assay to selectively identify 40 M. tuberculosis peptides from 19 proteins that most commonly copurify with serum vesicles of patients with TB. Here, we used this technology to evaluate if M. tuberculosis peptides can also be detected in individuals with latent TB infection (LTBI). Serum extracellular vesicles from 74 individuals presumed to have latent M. tuberculosis infection (LTBI) based on close contact with a household member with TB or a recent tuberculin skin test (TST) conversion were included in this study. Twenty-nine samples from individuals with no evidence of TB infection by TST and no known exposure to TB were used as controls to establish a threshold to account for nonspecific/background signal. We identified at least one of the 40 M. tuberculosis peptides in 70 (95%) individuals with LTBI. A single peptide from the glutamine synthetase (GlnA1) enzyme was identified in 61/74 (82%) individuals with LTBI, suggesting peptides from M. tuberculosis proteins involved in nitrogen metabolism might be candidates for pathogen-specific biomarkers for detection of LTBI. The detection of M. tuberculosis peptides in serum extracellular vesicles from persons with LTBI represents a potential advance in the diagnosis of LTBI. |
| Author | Mehaffy, Carolina Graham, Barbara Jarlsberg, Leah G Nahid, Payam Sterling, Timothy R Dobos, Karen M Kruh-Garcia, Nicole A Willyerd, Charis E Borisov, Andrey |
| Author_xml | – sequence: 1 givenname: Carolina surname: Mehaffy fullname: Mehaffy, Carolina organization: Proteomic and Metabolomics Facility, Colorado State University, Fort Collins, Colorado, USA – sequence: 2 givenname: Nicole A surname: Kruh-Garcia fullname: Kruh-Garcia, Nicole A organization: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA – sequence: 3 givenname: Barbara surname: Graham fullname: Graham, Barbara organization: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA – sequence: 4 givenname: Leah G surname: Jarlsberg fullname: Jarlsberg, Leah G organization: Division of Pulmonary and Critical Care Medicine, University of California San Francisco, Zuckerberg San Francisco General, San Francisco, California, USA – sequence: 5 givenname: Charis E surname: Willyerd fullname: Willyerd, Charis E organization: Clinical Data Science Associates, LLC, Fort Collins, Colorado, USA – sequence: 6 givenname: Andrey surname: Borisov fullname: Borisov, Andrey organization: Division of Tuberculosis Elimination, Centers for Disease Control and Prevention, Atlanta, Georgia, USA – sequence: 7 givenname: Timothy R surname: Sterling fullname: Sterling, Timothy R organization: Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA – sequence: 8 givenname: Payam surname: Nahid fullname: Nahid, Payam organization: Division of Pulmonary and Critical Care Medicine, University of California San Francisco, Zuckerberg San Francisco General, San Francisco, California, USA – sequence: 9 givenname: Karen M orcidid: 0000-0001-7115-8524 surname: Dobos fullname: Dobos, Karen M email: Karen.Dobos@colostate.edu organization: Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado, USA Karen.Dobos@colostate.edu |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/32245831$$D View this record in MEDLINE/PubMed |
| BookMark | eNpNkE9LAzEQxYNU7B-9eZYcvWxNstlu9iilaqVFwSreliQ7wcjupiZZtB_A7-0WK3iaN7wf7w0zRoPWtYDQOSVTSpm4up-vp4SkRZowcoRGlBQimc3I6-CfHqJxCO-EUM6z7AQNU8Z4JlI6Qt_LCtpojdUyWtdiZ_B6p52SOoK3XYNjp8DrrnbBBvwI22grCNi2-Al8by--opca6rqrpccvEKyue9941_S0D64N-NPGN7ySsS_Cm_9xy9aA3teeomMj6wBnhzlBzzeLzfwuWT3cLufXq0SngsdEGZWzGVBVSKMpF8AV5ECqXHPOC6Z61W-GUlNlKs2UBmmqKs9BayPAMDZBl7-5W-8-OgixbGzYXy9bcF0oWSpmrGCC5D16cUA71UBVbr1tpN-Vf69jP_ccdxI |
| CitedBy_id | crossref_primary_10_1016_j_dcit_2024_100020 crossref_primary_10_1099_jmm_0_001865 crossref_primary_10_1080_14737159_2022_2016395 crossref_primary_10_1111_jcmm_17836 crossref_primary_10_3390_ijms25052885 crossref_primary_10_3390_cells11010115 crossref_primary_10_3389_fimmu_2023_1254347 crossref_primary_10_1080_21505594_2023_2180934 crossref_primary_10_1093_discim_kyae011 crossref_primary_10_3389_fmicb_2021_589165 crossref_primary_10_1183_23120541_00113_2022 crossref_primary_10_1002_agt2_70018 crossref_primary_10_1080_17476348_2022_2093189 crossref_primary_10_3389_fimmu_2024_1339467 crossref_primary_10_3390_microorganisms12122405 crossref_primary_10_1371_journal_ppat_1009124 crossref_primary_10_3390_jcm10010145 crossref_primary_10_3389_fvets_2020_625067 crossref_primary_10_3389_fimmu_2021_628973 crossref_primary_10_3390_ijms26031155 crossref_primary_10_1016_j_bbrc_2022_06_021 crossref_primary_10_3390_microorganisms13071524 crossref_primary_10_3389_fcimb_2022_912831 crossref_primary_10_1183_16000617_0377_2020 crossref_primary_10_1038_s41598_023_38740_3 crossref_primary_10_1016_j_ab_2025_115829 crossref_primary_10_30699_ijmm_17_5_505 crossref_primary_10_3390_tropicalmed8020089 crossref_primary_10_1155_2021_6650670 |
| ContentType | Journal Article |
| Copyright | Copyright © 2020 Mehaffy et al. |
| Copyright_xml | – notice: Copyright © 2020 Mehaffy et al. |
| DBID | NPM 7X8 |
| DOI | 10.1128/JCM.00393-20 |
| DatabaseName | PubMed MEDLINE - Academic |
| DatabaseTitle | PubMed MEDLINE - Academic |
| DatabaseTitleList | PubMed MEDLINE - Academic |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | no_fulltext_linktorsrc |
| Discipline | Medicine Biology |
| EISSN | 1098-660X |
| ExternalDocumentID | 32245831 |
| Genre | Journal Article |
| GroupedDBID | --- .55 0R~ 18M 29K 2WC 39C 4.4 53G 5GY 5RE 5VS ABOCM ABPPZ ACGFO ADBBV AENEX AGVNZ ALMA_UNASSIGNED_HOLDINGS AOIJS BAWUL BTFSW CS3 D-I DIK DU5 E3Z EBS F5P FRP GX1 H13 HYE HZ~ KQ8 L7B NPM O9- OK1 P2P P6G RHF RHI RNS RPM RSF TR2 UCJ W8F WOQ X7M YIF ZCA ~KM 7X8 AAGFI |
| ID | FETCH-LOGICAL-c384t-bfb726e1b9afc148e4be7e0d7c44492b0d7e0df11fd5b35bceafdd77eccf8ef22 |
| IEDL.DBID | 7X8 |
| ISICitedReferencesCount | 32 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000582368300018&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 1098-660X |
| IngestDate | Thu Sep 04 16:33:58 EDT 2025 Wed Feb 19 02:30:11 EST 2025 |
| IsDoiOpenAccess | false |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 6 |
| Keywords | LTBI biomarker MRM-MS tuberculosis |
| Language | English |
| License | Copyright © 2020 Mehaffy et al. |
| LinkModel | DirectLink |
| MergedId | FETCHMERGED-LOGICAL-c384t-bfb726e1b9afc148e4be7e0d7c44492b0d7e0df11fd5b35bceafdd77eccf8ef22 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ORCID | 0000-0001-7115-8524 |
| OpenAccessLink | https://doi.org/10.1128/jcm.00393-20 |
| PMID | 32245831 |
| PQID | 2386292807 |
| PQPubID | 23479 |
| ParticipantIDs | proquest_miscellaneous_2386292807 pubmed_primary_32245831 |
| PublicationCentury | 2000 |
| PublicationDate | 20200526 |
| PublicationDateYYYYMMDD | 2020-05-26 |
| PublicationDate_xml | – month: 5 year: 2020 text: 20200526 day: 26 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States |
| PublicationTitle | Journal of clinical microbiology |
| PublicationTitleAlternate | J Clin Microbiol |
| PublicationYear | 2020 |
| SSID | ssj0014455 |
| Score | 2.495745 |
| Snippet | Identification of biomarkers for latent
infection and risk of progression to tuberculosis (TB) disease are needed to better identify individuals to target for... Identification of biomarkers for latent Mycobacterium tuberculosis infection and risk of progression to tuberculosis (TB) disease are needed to better identify... |
| SourceID | proquest pubmed |
| SourceType | Aggregation Database Index Database |
| Title | Identification of Mycobacterium tuberculosis Peptides in Serum Extracellular Vesicles from Persons with Latent Tuberculosis Infection |
| URI | https://www.ncbi.nlm.nih.gov/pubmed/32245831 https://www.proquest.com/docview/2386292807 |
| Volume | 58 |
| WOSCitedRecordID | wos000582368300018&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwpV1LS-RAEG5c3RUvurq-H7TgtTXJdF4nEVFUnGEOszK3oR_VMKCJTjKiP8D_bVUnw-xFWPASEkJCulNd_VXVV1WMneRKxsqpTMRhooWEXAncRoyICR3YIDXKR0wf7tNeLxsO837rcKtaWuVMJ3pFbUtDPvIz3FqSKKfaLefPL4K6RlF0tW2h8YMtdRDKkFSnw3kUQUrf9TSkmplJEgxnxPcoO7u77J76vFQRBV-DS7_JXK999_N-s9UWXvKLRh7W2QIUG-xX03DyfYMtd9tQ-h_20aToutZnx0vHu-8GV7ev3jx94vVUw8RMH8tqXPE-kV8sVHxccFQvePvqrZ4ocvsTj5U_QOX5dZzSVXjfw_iKk5OX3yOaLWo--Pd1ty0FrNhkf6-vBpc3ou3JIEwnk7XQTqdRAqHOlTNoSoHUkEJgUyOlzCONZ3jlwtDZWHdibUA5a9MUJcVl4KJoiy0WZQE7jGuLprmMs8BIkE5DhtCM0E4c2FiC6uyy49lUj1DmaUSqgHJajeaTvcu2m_81em6Kc4xQQVEoONz7j6f32UpE5nNARL8DtuRwxcMh-2le63E1OfLChMdev_sJRTrYgg |
| linkProvider | ProQuest |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Identification+of+Mycobacterium+tuberculosis+Peptides+in+Serum+Extracellular+Vesicles+from+Persons+with+Latent+Tuberculosis+Infection&rft.jtitle=Journal+of+clinical+microbiology&rft.au=Mehaffy%2C+Carolina&rft.au=Kruh-Garcia%2C+Nicole+A&rft.au=Graham%2C+Barbara&rft.au=Jarlsberg%2C+Leah+G&rft.date=2020-05-26&rft.eissn=1098-660X&rft.volume=58&rft.issue=6&rft_id=info:doi/10.1128%2FJCM.00393-20&rft_id=info%3Apmid%2F32245831&rft_id=info%3Apmid%2F32245831&rft.externalDocID=32245831 |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1098-660X&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1098-660X&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1098-660X&client=summon |