Comparative genomics and full-length Tprk profiling of < i > Treponema pallidum < /i > subsp. < i > pallidum < /i > reinfection

by Amin Addetia, Lauren C. Tantalo, Michelle J. Lin, Hong Xie, Meei-Li Huang, Christina M. Marra, Alexander L. Greninger Developing a vaccine againstTreponema pallidum subspeciespallidum, the causative agent of syphilis, remains a public health priority. Syphilis vaccine design efforts have been complicated by lack of an in vitroT.pallidum culture system, prolific antigenic variation in outer membrane protein TprK, and lack of functional annotation for nearly half of the genes. Understanding the genetic basis ofT.pallidum reinfection can provide insights into variation among strains that escape cross-protective immunity. Here, we present comparative genomic sequencing and deep, full-lengthtprK profiling of twoT.pallidum isolates from blood from the same patient that were collected six years apart. Notably, this patient was diagnosed with syphilis four times, with two of these episodes meeting the definition of neurosyphilis, during this interval. Outside of the highly variabletprK gene, we identified 14 coding changes in 13 genes. Nine of these genes putatively localized to the periplasmic or outer membrane spaces, consistent with a potential role in serological immunoevasion. Using a newly developed full-lengthtprK deep sequencing protocol, we profiled the diversity of this gene that far outpaces the rest of the genome. Intriguingly, we found that the reinfecting isolate demonstrated less diversity across eachtprK variable region compared to the isolate from the first infec...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research