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We performed a genetic screen in <jats:italic>F. novicida<\/jats:italic> to decipher the molecular basis for regulated OMV\/T formation, and identified both hypo\u2010 and hyper\u2010vesiculating mutants. Mutations in <jats:italic>fumA<\/jats:italic> and <jats:italic>tktA<\/jats:italic>, involved in central carbon metabolism, and in FTN_0908 and FTN_1037, of unknown function, resulted in severe defects in OMV\/T production. Cysteine deprivation was identified as the signal that triggers OMV\/T formation in <jats:italic>F. novicida<\/jats:italic> during growth in rich medium. We also found that fully virulent <jats:italic>F. tularensis<\/jats:italic> produces OMV\/T in a similarly regulated manner. Further analysis revealed that OMV\/T production is responsive to deprivation of essential amino acids in addition to cysteine, and that the hypo\u2010vesiculating mutants are defective in responding to this signal. Thus, amino acid starvation, such as encountered by <jats:italic>Francisella<\/jats:italic> during host cell invasion, regulates the production of membrane\u2010derived structures.<\/jats:p>","DOI":"10.1111\/mmi.13897","type":"journal-article","created":{"date-parts":[[2017,12,14]],"date-time":"2017-12-14T13:56:42Z","timestamp":1513259802000},"page":"523-541","source":"Crossref","is-referenced-by-count":47,"title":["Amino acid deprivation and central carbon metabolism regulate the production of outer membrane vesicles and tubes by <i>Francisella<\/i>"],"prefix":"10.1111","volume":"107","author":[{"given":"Vinaya","family":"Sampath","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Center for Infectious Diseases Stony Brook University Stony Brook NY 11794 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William D.","family":"McCaig","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Center for Infectious Diseases Stony Brook University Stony Brook NY 11794 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9798-9040","authenticated-orcid":false,"given":"David G.","family":"Thanassi","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Center for Infectious Diseases Stony Brook University Stony Brook NY 11794 USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,3]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2010.05.008"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/iai.59.9.3291-3296.1991"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0206079"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-2920.2010.02229.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.02488-14"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000382"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr418"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0050473"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01250-06"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.13.2.232-235.1965"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.0030084"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0601838103"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.6.3204-3217.2004"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01485-08"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.02.005"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.06731.x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.2144\/000112604"},{"key":"e_1_2_7_19_1","article-title":"Contrasting lifestyles within the host cell","volume":"4","author":"Russo Case E.","year":"2016","journal-title":"Microbiology Spectrum"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-2952(02)01172-3"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2007.05928.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.15.4.631-646.2002"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.10.008"},{"key":"e_1_2_7_24_1","unstructured":"Federal Select Agent Program. 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