{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,13]],"date-time":"2025-12-13T06:52:48Z","timestamp":1765608768884,"version":"3.41.2"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2020,11,17]],"date-time":"2020-11-17T00:00:00Z","timestamp":1605571200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,16]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Tuberculosis (TB) is the most important infectious disease worldwide, based on the number of new cases and deaths reported by the World Health Organization. Several vaccine candidates against TB have been characterized at preclinical and clinical levels. The BCG\u0394BCG1419c vaccine candidate, which lacks the BCG1419c gene that encodes for a c-di-GMP phosphodiesterase, provides improved efficacy against chronic TB, reactivation from latent-like infection and against chronic TB in the presence of type 2 diabetes in murine models. We previously reported that compared with wild type BCG, BCG\u0394BCG1419c changed levels of several proteins. Here, using a label-free proteomic approach, we confirmed that a novel, second-generation version of BCG\u0394BCG1419c maintains changes in antigenic proteins already reported, and here we further found differences in secreted proteins, as well as that this new BCG\u0394BCG1419c version modifies its production of proteins involved in redox and nitrogen\/protein metabolism compared with wild type BCG. This work contributes to the proteomic characterization of a novel vaccine candidate that is more effective against TB than parental BCG in diverse murine models.<\/jats:p>","DOI":"10.1093\/femspd\/ftaa070","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T20:11:12Z","timestamp":1605298272000},"source":"Crossref","is-referenced-by-count":15,"title":["Proteomic characterization of a second-generation version of the BCG\u0394BCG1419c vaccine candidate by means of electrospray-ionization quadrupole time-of-flight mass spectrometry"],"prefix":"10.1093","volume":"79","author":[{"given":"Jes\u00fas Bernardino","family":"Vel\u00e1zquez-Fern\u00e1ndez","sequence":"first","affiliation":[{"name":"CONACYT-CIATEJ, Tecnolog\u00eda Ambiental, Av. Normalistas 800, Col. Colinas de la Normal, 44270 Guadalajara, Jalisco, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gustavo Henrique Martins","family":"Ferreira-Souza","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Research & Development Laboratory, SpectraMass Limited, Campinas, S\u00e3o Paulo, Brazil. Rua Monteiro Lobato, 255 - Cidade Universit\u00e1ria, Campinas - SP, 13083-862, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacobo","family":"Rodr\u00edguez-Campos","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n y Asistencia en Tecnolog\u00eda y dise\u00f1o del Estado de Jalisco (CIATEJ), A. C., Unidad de Servicios Anal\u00edticos y Metrol\u00f3gicos, Av. Normalistas 800, Col. Colinas de la Normal, 44270 Guadalajara, Jalisco, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel de Jes\u00fas","family":"Aceves-S\u00e1nchez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n y Asistencia en Tecnolog\u00eda y dise\u00f1o del Estado de Jalisco (CIATEJ), A.C., Biotecnolog\u00eda M\u00e9dica y Farmac\u00e9utica, Av. Normalistas 800, Col. Colinas de la Normal, 44270 Guadalajara, Jalisco, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Bravo-Madrigal","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n y Asistencia en Tecnolog\u00eda y dise\u00f1o del Estado de Jalisco (CIATEJ), A.C., Biotecnolog\u00eda M\u00e9dica y Farmac\u00e9utica, Av. Normalistas 800, Col. Colinas de la Normal, 44270 Guadalajara, Jalisco, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alba Adriana","family":"Vallejo-Cardona","sequence":"additional","affiliation":[{"name":"CONACYT-CIATEJ, Biotecnolog\u00eda M\u00e9dica y Farmac\u00e9utica, Av. Normalistas 800, Col. Colinas de la Normal, 44270 Guadalajara, Jalisco, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4125-1370","authenticated-orcid":false,"given":"Mario Alberto","family":"Flores-Valdez","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n y Asistencia en Tecnolog\u00eda y dise\u00f1o del Estado de Jalisco (CIATEJ), A.C., Biotecnolog\u00eda M\u00e9dica y Farmac\u00e9utica, Av. Normalistas 800, Col. Colinas de la Normal, 44270 Guadalajara, Jalisco, M\u00e9xico"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,11,17]]},"reference":[{"key":"2021011621443244400_bib1","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/S0076-6879(08)36018-2","article-title":"Scavenging of reactive nitrogen species by mycobacterial truncated hemoglobins","volume":"436","author":"Ascenzi","year":"2008","journal-title":"Method Enzymol"},{"key":"2021011621443244400_bib2","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1016\/j.tube.2009.07.003","article-title":"Identification of proteins from tuberculin purified protein derivative (PPD) by LC-MS\/MS","volume":"89","author":"Borsuk","year":"2009","journal-title":"Tuberculosis"},{"key":"2021011621443244400_bib3","doi-asserted-by":"crossref","first-page":"811","DOI":"10.4014\/jmb.1911.11043","article-title":"Transcriptional and mycolic acid profiling in Mycobacterium bovis BCG in vitro show an effect for c-di-GMP and overlap between dormancy and biofilms","volume":"30","author":"Cruz-Villegas","year":"2020","journal-title":"J Microbiol Biotechnol"},{"key":"2021011621443244400_bib4","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/iub.1353","article-title":"The cyclic di-GMP phosphodiesterase gene Rv1357c\/BCG1419c affects BCG Pellicle production and in vivo maintenance","volume":"67","author":"Flores-Valdez","year":"2015","journal-title":"IUBMB Life"},{"key":"2021011621443244400_bib5","first-page":"1281","article-title":"The BCG\u0394BCG1419c Vaccine Candidate Reduces Lung Pathology, IL-6, TNF-\u03b1, and IL-10 During Chronic TB Infection","volume":"9","author":"Flores-Valdez","year":"2018","journal-title":"Front Microbiol"},{"key":"2021011621443244400_bib6","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1002\/pmic.200800562","article-title":"The detection, correlation, and comparison of peptide precursor and product ions from data independent LC-MS with data dependent LC-MS\/MS","volume":"9","author":"Geromanos","year":"2009","journal-title":"Proteomics"},{"key":"2021011621443244400_bib7","doi-asserted-by":"crossref","DOI":"10.1128\/microbiolspec.MTBP-0001-2016","article-title":"Breaking transmission with vaccines: the case of tuberculosis","volume":"5","author":"Gonzalo-Asensio","year":"2017","journal-title":"Microbiol Spectr"},{"key":"2021011621443244400_bib8","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1111\/mmi.12127","article-title":"A novel F(420)-dependent anti-oxidant mechanism protects Mycobacterium tuberculosis against oxidative stress and bactericidal agents","volume":"87","author":"Gurumurthy","year":"2013","journal-title":"Mol Microbiol"},{"key":"2021011621443244400_bib1_760_265720","article-title":"Potential impact of tuberculosis vaccines in China, South Africa, and India","volume":"12","author":"Harris","year":"2020","journal-title":"Sci Transl Med"},{"key":"2021011621443244400_bib9","doi-asserted-by":"crossref","first-page":"e1002152","DOI":"10.1371\/journal.pmed.1002152","article-title":"The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling","volume":"13","author":"Houben","year":"2016","journal-title":"PLoS Med"},{"key":"2021011621443244400_bib10","doi-asserted-by":"crossref","first-page":"E5834","DOI":"10.1073\/pnas.1510932112","article-title":"E1 of alpha-ketoglutarate dehydrogenase defends Mycobacterium tuberculosis against glutamate anaplerosis and nitroxidative stress","volume":"112","author":"Maksymiuk","year":"2015","journal-title":"Proc Natl Acad Sci USA"},{"key":"2021011621443244400_bib11","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1093\/trstmh\/trw006","article-title":"Drug-resistant TB: deadly, costly and in need of a vaccine","volume":"110","author":"Manjelievskaia","year":"2016","journal-title":"Trans R Soc Trop Med Hyg"},{"key":"2021011621443244400_bib12","doi-asserted-by":"crossref","first-page":"22922","DOI":"10.1038\/srep22922","article-title":"Efficient and simple generation of multiple unmarked gene deletions in Mycobacterium smegmatis","volume":"6","author":"Mao","year":"2016","journal-title":"Sci Rep"},{"key":"2021011621443244400_bib13","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1002\/pmic.200900836","article-title":"Descriptive proteomic analysis shows protein variability between closely related clinical isolates of Mycobacterium tuberculosis","volume":"10","author":"Mehaffy","year":"2010","journal-title":"Proteomics"},{"key":"2021011621443244400_bib14","doi-asserted-by":"crossref","first-page":"16791","DOI":"10.1038\/s41598-019-53069-6","article-title":"Mycobacterium tuberculosis CysA2 is a dual sulfurtransferase with activity against thiosulfate and 3-mercaptopyruvate and interacts with mammalian cells","volume":"9","author":"Meza","year":"2019","journal-title":"Sci Rep"},{"key":"2021011621443244400_bib15","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1586\/14760584.2015.1089175","article-title":"Current efforts and future prospects in the development of live mycobacteria as vaccines","volume":"14","author":"Ng","year":"2015","journal-title":"Expert Rev Vaccines"},{"key":"2021011621443244400_bib16","doi-asserted-by":"crossref","first-page":"121","DOI":"10.3389\/fimmu.2018.00121","article-title":"Next-generation vaccines based on bacille calmette-guerin","volume":"9","author":"Nieuwenhuizen","year":"2018","journal-title":"Front Immunol"},{"key":"2021011621443244400_bib17","doi-asserted-by":"crossref","first-page":"4763","DOI":"10.1016\/j.vaccine.2016.08.035","article-title":"The BCG\u0394BCG1419c strain, which produces more pellicle in vitro, improves control of chronic tuberculosis in vivo","volume":"34","author":"Pedroza-Rold\u00e1n","year":"2016","journal-title":"Vaccine"},{"key":"2021011621443244400_bib18","doi-asserted-by":"crossref","first-page":"102761","DOI":"10.1016\/j.ebiom.2020.102761","article-title":"Live attenuated TB vaccines representing the three modern Mycobacterium tuberculosis lineages reveal that the Euro-American genetic background confers optimal vaccine potential","volume":"55","author":"Perez","year":"2020","journal-title":"EBioMedicine"},{"key":"2021011621443244400_bib19","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1186\/1559-0275-10-8","article-title":"Proteomic analysis of purified protein derivative of Mycobacterium tuberculosis","volume":"10","author":"Prasad","year":"2013","journal-title":"Clin Proteom"},{"key":"2021011621443244400_bib20","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2019.00532","article-title":"BCG Vaccination Prevents Reactivation of Latent Lymphatic Murine Tuberculosis Independently of CD4+ T Cells","volume":"10","author":"Sathkumara","year":"2019","journal-title":"Front Immunol"},{"key":"2021011621443244400_bib22","doi-asserted-by":"crossref","first-page":"2069","DOI":"10.1016\/j.vaccine.2018.03.014","article-title":"Immune response elicited by two rBCG strains devoid of genes involved in c-di-GMP metabolism affect protection versus challenge with M. tuberculosis strains of different virulence","volume":"36","author":"Segura-Cerda","year":"2018","journal-title":"Vaccine"},{"key":"2021011621443244400_bib21","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1038\/s41541-020-0169-6","article-title":"BCG and BCG\u0394BCG1419c protect type 2 diabetic mice against tuberculosis via different participation of T and B lymphocytes, dendritic cells and pro-inflammatory cytokines","volume":"5","author":"Segura-Cerda","year":"2020","journal-title":"NPJ Vaccines"},{"key":"2021011621443244400_bib23","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1074\/mcp.M500230-MCP200","article-title":"Absolute quantification of proteins by LCMSE - A virtue of parallel MS acquisition","volume":"5","author":"Silva","year":"2006","journal-title":"Mol Cell Prot"},{"key":"2021011621443244400_bib24","doi-asserted-by":"crossref","DOI":"10.1186\/s12866-017-0925-6","article-title":"A shift in the virulence potential of Corynebacterium pseudotuberculosis biovar ovis after passage in a murine host demonstrated through comparative proteomics","volume":"17","author":"Silva","year":"2017","journal-title":"BMC Microbiol"},{"key":"2021011621443244400_bib25","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1007\/978-1-4939-6730-8_4","article-title":"LC-MS(E), multiplex MS\/MS, ion mobility, and label-free quantitation in clinical proteomics","volume":"1546","author":"Souza","year":"2017","journal-title":"Methods Mol Biol"},{"key":"2021011621443244400_bib26","doi-asserted-by":"crossref","first-page":"9440","DOI":"10.1073\/pnas.1530509100","article-title":"Statistical significance for genomewide studies","volume":"100","author":"Storey","year":"2003","journal-title":"Proc Natl Acad Sci"},{"key":"2021011621443244400_bib27","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/nmeth996","article-title":"Recombineering in Mycobacterium tuberculosis","volume":"4","author":"van\u00a0Kessel","year":"2007","journal-title":"Nat Methods"},{"article-title":"Global Tuberculosis Report 2018","year":"2018","author":"WHO","key":"2021011621443244400_bib28"},{"key":"2021011621443244400_bib29","doi-asserted-by":"crossref","first-page":"6023","DOI":"10.1021\/ac0346196","article-title":"Enzyme-friendly, mass spectrometry-compatible surfactant for in-solution enzymatic digestion of proteins","volume":"75","author":"Yu","year":"2003","journal-title":"Anal Chem"}],"container-title":["Pathogens and Disease"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/femspd\/advance-article-pdf\/doi\/10.1093\/femspd\/ftaa070\/34364066\/ftaa070.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/femspd\/article-pdf\/79\/1\/ftaa070\/35905074\/ftaa070.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/femspd\/article-pdf\/79\/1\/ftaa070\/35905074\/ftaa070.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,11,28]],"date-time":"2022-11-28T01:18:31Z","timestamp":1669598311000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/femspd\/article\/doi\/10.1093\/femspd\/ftaa070\/5986614"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,17]]},"references-count":30,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2021,1,16]]}},"URL":"https:\/\/doi.org\/10.1093\/femspd\/ftaa070","relation":{},"ISSN":["2049-632X"],"issn-type":[{"type":"electronic","value":"2049-632X"}],"subject":[],"published-other":{"date-parts":[[2021,2]]},"published":{"date-parts":[[2020,11,17]]},"article-number":"ftaa070"}}