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In this study, the RNA transcript profiles of the <jats:italic>T<\/jats:italic>. <jats:italic>pallidum<\/jats:italic> Nichols during <jats:italic>in vitro<\/jats:italic> culture and rabbit infection were compared to examine whether gene expression patterns differed in these two environments. To this end, RNA preparations were converted to cDNA and subjected to RNA-seq using high throughput Illumina sequencing; reverse transcriptase quantitative PCR was also performed on selected genes for validation of results. The transcript profiles in the <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> environments were remarkably similar, exhibiting a high degree of concordance overall. However, transcript levels of 94 genes (9%) out of the 1,063 predicted genes in the <jats:italic>T<\/jats:italic>. <jats:italic>pallidum<\/jats:italic> genome were significantly different during rabbit infection versus <jats:italic>in vitro<\/jats:italic> culture, varying by up to 8-fold in the two environments. Genes that exhibited significantly higher transcript levels during rabbit infection included those encoding multiple ribosomal proteins, several prominent membrane proteins, glycolysis-associated enzymes, replication initiator DnaA, rubredoxin, thioredoxin, two putative regulatory proteins, and proteins associated with solute transport. <jats:italic>In vitro<\/jats:italic> cultured <jats:italic>T<\/jats:italic>. <jats:italic>pallidum<\/jats:italic> had higher transcript levels of DNA repair proteins, cofactor synthesis enzymes, and several hypothetical proteins. The overall concordance of the transcript profiles may indicate that these environments are highly similar in terms of their effects on <jats:italic>T<\/jats:italic>. <jats:italic>pallidum<\/jats:italic> physiology and growth, and may also reflect a relatively low level of transcriptional regulation in this reduced genome organism.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009949","type":"journal-article","created":{"date-parts":[[2021,9,27]],"date-time":"2021-09-27T19:56:32Z","timestamp":1632772592000},"page":"e1009949","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":33,"title":["Comparison of transcriptional profiles of Treponema pallidum during experimental infection of rabbits and in vitro culture: Highly similar, yet different"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1354-1407","authenticated-orcid":true,"given":"Bridget D.","family":"De Lay","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6608-6551","authenticated-orcid":true,"given":"Todd A.","family":"Cameron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2249-7073","authenticated-orcid":true,"given":"Nicholas R.","family":"De Lay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Norris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3702-9715","authenticated-orcid":true,"given":"Diane G.","family":"Edmondson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,9,27]]},"reference":[{"key":"ppat.1009949.ref001","volume-title":"Pathogenic Treponema: molecular and cellular biology","author":"JD Radolf","year":"2006"},{"issue":"12","key":"ppat.1009949.ref002","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/nrmicro.2016.141","article-title":"Treponema pallidum, the syphilis spirochete: making a living as a stealth pathogen","volume":"14","author":"JD Radolf","year":"2016","journal-title":"Nat Rev Microbiol"},{"issue":"1","key":"ppat.1009949.ref003","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1128\/CMR.19.1.29-49.2006","article-title":"Biological basis for syphilis","volume":"19","author":"RE LaFond","year":"2006","journal-title":"Clin Microbiol Rev"},{"issue":"33","key":"ppat.1009949.ref004","article-title":"The pan-genome of Treponema pallidum reveals differences in genome plasticity between subspecies related to venereal and non-venereal syphilis","volume":"21","author":"AK Jaiswal","year":"2020","journal-title":"BMC Genomics"},{"issue":"12","key":"ppat.1009949.ref005","doi-asserted-by":"crossref","first-page":"e0143304","DOI":"10.1371\/journal.pone.0143304","article-title":"Global estimates of the prevalence and incidence of four curable sexually transmitted infections in 2012 based on systematic review and global reporting.","volume":"10","author":"L Newman","year":"2015","journal-title":"PLoS One."},{"issue":"6","key":"ppat.1009949.ref006","doi-asserted-by":"crossref","first-page":"e1002330","DOI":"10.1371\/journal.pmed.1002330","article-title":"Assessing process, content, and politics in developing the global health sector strategy on sexually transmitted infections 2016\u20132021: Implementation opportunities for policymakers.","volume":"14","author":"A Seale","year":"2017","journal-title":"PLoS Med."},{"issue":"7","key":"ppat.1009949.ref007","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0159309","article-title":"Syphilis trends among men who have sex with men in the United States and western Europe: a systematic review of trend studies published between 2004 and 2015.","volume":"11","author":"WE Abara","year":"2016","journal-title":"PLoS ONE."},{"issue":"8","key":"ppat.1009949.ref008","doi-asserted-by":"crossref","first-page":"e0183409","DOI":"10.1371\/journal.pone.0183409","article-title":"The current status of syphilis prevention and control in Jiangsu province, China: a cross-sectional study.","volume":"12","author":"YF Chen","year":"2017","journal-title":"PLoS One."},{"issue":"2","key":"ppat.1009949.ref009","doi-asserted-by":"crossref","first-page":"177","DOI":"10.2217\/fmb.12.148","article-title":"Old foes, new challenges: syphilis, cholera and TB.","volume":"8","author":"LV Stamm","year":"2013","journal-title":"Future Microbiol."},{"key":"ppat.1009949.ref010","unstructured":"Prevention CfDCa. 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