title: Transcription of TP0126, Treponema pallidum putative OmpW homolog, is regulated by the length of a homopolymeric guanosine repeat.
abstract: An effective mechanism for introduction of phenotypic diversity within a bacterial population exploits changes in the length of repetitive DNA elements located within gene promoters. This phenomenon, known as phase variation, causes rapid activation or silencing of gene expression and fosters bacterial adaptation to new or changing environments. Phase variation often occurs in surface-exposed proteins, and in Treponema pallidum subsp. pallidum, the syphilis agent, it was reported to affect transcription of three putative outer membrane protein (OMP)-encoding genes. When the T. pallidum subsp. pallidum Nichols strain genome was initially annotated, the TP0126 open reading frame was predicted to include a poly(G) tract and did not appear to have a predicted signal sequence that might suggest the possibility of its being an OMP. Here we show that the initial annotation was incorrect, that this poly(G) is instead located within the TP0126 promoter, and that it varies in length in vivo during experimental syphilis. Additionally, we show that TP0126 transcription is affected by changes in the poly(G) length consistent with regulation by phase variation. In silico analysis of the TP0126 open reading frame based on the experimentally identified transcriptional start site shortens this hypothetical protein by 69 amino acids, reveals a predicted cleavable signal peptide, and suggests structural homology with the OmpW family of porins. Circular dichroism of recombinant TP0126 supports structural homology to OmpW. Together with the evidence that TP0126 is fully conserved among T. pallidum subspecies and strains, these data suggest an important role for TP0126 in T. pallidum biology and syphilis pathogenesis.
authors: Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA Department of Global Health, University of Washington, Seattle, Washington, USA giacal@u.washington.edu.
authors: Lorenzo
authors: L
authors: Giacani
authors: Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
authors: Stephanie L
authors: SL
authors: Brandt
authors: Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA Graduate School, Southern Medical University, Guangzhou, People's Republic of China, and Division of STD, Guangdong Provincial Center for STI & Skin Diseases Control and Prevention, Guangzhou, People's Republic of China.
authors: Wujian
authors: W
authors: Ke
authors: Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
authors: Tara B
authors: TB
authors: Reid
authors: Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
authors: Barbara J
authors: BJ
authors: Molini
authors: Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
authors: Stefanie
authors: S
authors: Iverson-Cabral
authors: Department of Dermatology, IRCCS Azienda Universitaria Ospedaliera San Martino-IST, Genoa, Italy.
authors: Giulia
authors: G
authors: Ciccarese
authors: Department of Dermatology, IRCCS Azienda Universitaria Ospedaliera San Martino-IST, Genoa, Italy.
authors: Francesco
authors: F
authors: Drago
authors: Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA Department of Global Health, University of Washington, Seattle, Washington, USA.
authors: Sheila A
authors: SA
authors: Lukehart
authors: Department of Medicine, Division of Allergy and Infectious Diseases, University of Washington, Seattle, Washington, USA.
authors: Arturo
authors: A
authors: Centurion-Lara
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology*; D006151:Guanosine / Q000737:chemistry*; D006801:Humans; D056724:Immunity, Humoral; D008958:Models, Molecular; D011487:Protein Conformation; D011817:Rabbits; D011994:Recombinant Proteins / Q000378:metabolism; D013587:Syphilis / Q000382:microbiology; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D014210:Treponema pallidum / Q000378:metabolism*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D011994:Recombinant Proteins; D006151:Guanosine