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In support of a stepwise process regulating biofilm production in mycobacteria, it was shown\u00a0elsewhere that <jats:italic>lsr2<\/jats:italic> participates in intercellular aggregation, while <jats:italic>groEL1<\/jats:italic> was required for biofilm maturation in <jats:italic>M. smegmatis<\/jats:italic>. Here, by means of RNA-Seq, we monitored the early steps of biofilm production in <jats:italic>M. bovis<\/jats:italic> BCG, to distinguish intercellular aggregation from attachment to a surface. Genes encoding for the transcriptional regulators <jats:italic>dosR<\/jats:italic> and <jats:italic>BCG0114<\/jats:italic> (<jats:italic>Rv0081<\/jats:italic>) were significantly regulated and responded differently to intercellular aggregation and surface attachment. Moreover, a <jats:italic>M. tuberculosis<\/jats:italic> H37Rv deletion mutant in the <jats:italic>Rv3134c-dosS-dosR<\/jats:italic> regulon, formed less biofilm than wild type <jats:italic>M. tuberculosis<\/jats:italic>, a phenotype reverted upon reintroduction of this operon into the mutant. Combining RT-qPCR with microbiological assays (colony and surface pellicle morphologies, biofilm quantification, Ziehl\u2013Neelsen staining, growth curve and replication of planktonic cells), we found that <jats:italic>BCG0642c<\/jats:italic> affected biofilm production and replication of planktonic BCG, whereas <jats:italic>ethR<\/jats:italic> affected only phenotypes linked to planktonic cells despite its downregulation at the intercellular aggregation step. Our results provide evidence for a stage-dependent expression of genes that contribute to biofilm production in slow-growing mycobacteria.<\/jats:p>","DOI":"10.1038\/s41598-020-69152-2","type":"journal-article","created":{"date-parts":[[2020,7,28]],"date-time":"2020-07-28T10:04:50Z","timestamp":1595930690000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Transcriptional portrait of M. bovis BCG during biofilm production shows genes differentially expressed during intercellular aggregation and substrate attachment"],"prefix":"10.1038","volume":"10","author":[{"given":"Mario Alberto","family":"Flores-Valdez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel de Jes\u00fas","family":"Aceves-S\u00e1nchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliza J. R.","family":"Peterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitin","family":"Baliga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Bravo-Madrigal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel \u00c1ngel","family":"De la Cruz-Villegas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel A.","family":"Ares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Born","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Voskuil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayeli Areli","family":"P\u00e9rez-Padilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirna","family":"Burciaga-Flores","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanya Amanda","family":"Camacho-Villegas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Guadalupe","family":"Espinoza-Jorge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,7,28]]},"reference":[{"key":"69152_CR1","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1111\/mmi.13734","volume":"105","author":"Y Yang","year":"2017","unstructured":"Yang, Y. et al. 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