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In fleas competent to transmit<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>, low-GC-content genes<jats:italic>y3555<\/jats:italic>,<jats:italic>y3551,<\/jats:italic>and<jats:italic>y3550<\/jats:italic>are highly transcribed, suggesting that these genes have a highly prioritized role in flea infection. Here, we demonstrate that<jats:italic>y3555<\/jats:italic>,<jats:italic>y3551,<\/jats:italic>and<jats:italic>y3550<\/jats:italic>are transcribed as part of a single polycistronic mRNA comprising the<jats:italic>y3555, y3554, y3553<\/jats:italic>,<jats:italic>y355x, y3551<\/jats:italic>, and<jats:italic>y3550<\/jats:italic>genes. Additionally,<jats:italic>y355x-y3551-y3550<\/jats:italic>compose another operon, while<jats:italic>y3550<\/jats:italic>can be also transcribed as a monocistronic mRNA. The expression of these genes is induced by hyperosmotic salinity stress, which serves as an explicit environmental stimulus that initiates transcriptional activity from the predicted<jats:italic>y3550<\/jats:italic>promoter. Y3555 has homology to pyridoxal 5\u2032-phosphate (PLP)-dependent aromatic aminotransferases, while Y3550 and Y3551 are homologous to the Rid protein superfamily (YjgF\/YER057c\/UK114) members that forestall damage caused by reactive intermediates formed during PLP-dependent enzymatic activity. We demonstrate that<jats:italic>y3551<\/jats:italic>specifically encodes an archetypal RidA protein with 2-aminoacrylate deaminase activity but Y3550 lacks Rid deaminase function. Heterologous expression of<jats:italic>y3555<\/jats:italic>generates a critical aspartate requirement in a<jats:named-content content-type=\"genus-species\">Salmonella enterica<\/jats:named-content><jats:italic>aspC<\/jats:italic>mutant, while its<jats:italic>in vitro<\/jats:italic>expression, and specifically its heterologous coexpression with<jats:italic>y3550,<\/jats:italic>enhances the growth rate of an<jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\u0394<jats:italic>aspC<\/jats:italic>\u0394<jats:italic>tyrB<\/jats:italic>mutant in a defined minimal amino acid-supplemented medium. Our data suggest that the<jats:italic>y3555, y3551<\/jats:italic>, and<jats:italic>y3550<\/jats:italic>genes operate cooperatively to optimize aromatic amino acid metabolism and are induced under conditions of hyperosmotic salinity stress.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>Distinct gene repertoires are expressed during<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>infection of its flea and mammalian hosts. The functions of many of these genes remain predicted or unknown, necessitating their characterization, as this may provide a better understanding of<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>specialized biological adaptations to the discrete environments of its two hosts. This study provides functional context to adjacently clustered horizontally acquired genes predominantly expressed in the flea host by deciphering their fundamental processes with regard to (i) transcriptional organization, (ii) transcription activation signals, and (iii) biochemical function. Our data support a role for these genes in osmoadaptation and aromatic amino acid metabolism, highlighting these as preferential processes by which<jats:named-content content-type=\"genus-species\">Y. pestis<\/jats:named-content>gene expression is modulated during flea infection.<\/jats:p>","DOI":"10.1128\/jb.00733-19","type":"journal-article","created":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T11:12:21Z","timestamp":1584702741000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Putative Horizontally Acquired Genes, Highly Transcribed during<i>Yersinia pestis<\/i>Flea Infection, Are Induced by Hyperosmotic Stress and Function in Aromatic Amino Acid Metabolism"],"prefix":"10.1128","volume":"202","author":[{"given":"Luary C.","family":"Mart\u00ednez-Chavarr\u00eda","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janelle","family":"Sagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Irons","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela K.","family":"Hinz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athena","family":"Lemon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Telmo","family":"Gra\u00e7a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana M.","family":"Downs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viveka","family":"Vadyvaloo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","published-online":{"date-parts":[[2020,5,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"17837","DOI":"10.1073\/pnas.0408026101","article-title":"Microevolution and history of the plague bacillus, Yersinia pestis","volume":"101","author":"Achtman","year":"2004","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B2","doi-asserted-by":"publisher","first-page":"14043","DOI":"10.1073\/pnas.96.24.14043","article-title":"Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis","volume":"96","author":"Achtman","year":"1999","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1038\/ng.705","article-title":"Yersinia pestis genome sequencing identifies patterns of global phylogenetic diversity","volume":"42","author":"Morelli","year":"2010","journal-title":"Nat Genet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1051\/vetres:2008039","article-title":"Adaptive strategies of Yersinia pestis to persist during inter-epizootic and epizootic periods","volume":"40","author":"Eisen","year":"2009","journal-title":"Vet Res"},{"key":"B5","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/978-3-540-75418-3_11","article-title":"Yersinia pestis biofilm in the flea vector and its role in the transmission of plague","volume":"322","author":"Hinnebusch","year":"2008","journal-title":"Curr Top Microbiol Immunol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1126\/science.273.5273.367","article-title":"Role of the Yersinia pestis hemin storage (hms) locus in the transmission of plague by fleas","volume":"273","author":"Hinnebusch","year":"1996","journal-title":"Science"},{"key":"B7","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1146\/annurev-micro-090816-093521","article-title":"\u201cFleaing\u201d the plague: adaptations of Yersinia pestis to its insect vector that lead to transmission","volume":"71","author":"Hinnebusch","year":"2017","journal-title":"Annu Rev Microbiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.mib.2012.02.003","article-title":"Yersinia\u2013flea interactions and the evolution of the arthropod-borne transmission route of plague","volume":"15","author":"Chouikha","year":"2012","journal-title":"Curr Opin Microbiol"},{"key":"B9","unstructured":"9. 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