High-throughput nanopore sequencing of Treponema pallidum tandem repeat genes arp and tp0470 reveals clade-specific patterns and recapitulates global whole genome phylogeny.

Autor:	Lieberman NAP; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, United States., Armstrong TD; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, United States., Chung B; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, United States., Pfalmer D; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, United States., Hennelly CM; Division of Infectious Diseases, Institute for Global Health and Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States., Haynes A; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States., Romeis E; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States., Wang QQ; Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; National Center for STD Control, China Centers for Disease Control and Prevention, Nanjing, China., Zhang RL; Department of Dermatology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China., Kou CX; Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.; National Center for STD Control, China Centers for Disease Control and Prevention, Nanjing, China., Ciccarese G; Section of Dermatology, Department of Health Sciences, San Martino University Hospital, Genoa, Italy., Conte ID; Sexual Health Center, Department of Prevention, ASL Città di Torino, Turin, Italy., Cusini M; Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy., Drago F; Section of Dermatology, Department of Health Sciences, San Martino University Hospital, Genoa, Italy., Nakayama SI; Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan., Lee K; Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan., Ohnishi M; Department of Bacteriology I, National Institute of Infectious Diseases, Tokyo, Japan., Konda KA; Unit of Health, Sexuality and Human Development, Laboratory of Sexual Health, Universidad Peruana Cayetano-Heredia, Lima, Peru.; Keck School of Medicine, University of Southern California, Los Angeles, CA, United States., Vargas SK; Unit of Health, Sexuality and Human Development, Laboratory of Sexual Health, Universidad Peruana Cayetano-Heredia, Lima, Peru.; School of Public Health and Administration 'Carlos Vidal Layseca', Universidad Peruana Cayetano Heredia, Lima, Peru., Eguiluz M; Unit of Health, Sexuality and Human Development, Laboratory of Sexual Health, Universidad Peruana Cayetano-Heredia, Lima, Peru., Caceres CF; Unit of Health, Sexuality and Human Development, Laboratory of Sexual Health, Universidad Peruana Cayetano-Heredia, Lima, Peru., Klausner JD; Keck School of Medicine, University of Southern California, Los Angeles, CA, United States., Mitja O; Fight Aids and Infectious Diseases Foundation, Hospital Germans Trias i Pujol, Barcelona, Spain.; Lihir Medical Centre, International SOS, Londolovit, Papua New Guinea., Rompalo A; Department of Infectious Diseases, Johns Hopkins Medical Institutions, Baltimore, MD, United States., Mulcahy F; Department of Genito Urinary Medicine and Infectious Diseases, St. James's Hospital, Dublin, Ireland., Hook EW 3rd; Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, United States.; Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, United States.; Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, United States., Hoffman IF; Division of Infectious Diseases, Institute for Global Health and Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.; UNC Project-Malawi, Lilongwe, Malawi., Matoga MM; Division of Infectious Diseases, Institute for Global Health and Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States.; UNC Project-Malawi, Lilongwe, Malawi., Zheng H; Dermatology Hospital of Southern Medical University, Guangzhou, China.; Institute for Global Health and Sexually Transmitted Infections, Guangzhou, China., Yang B; Dermatology Hospital of Southern Medical University, Guangzhou, China.; Institute for Global Health and Sexually Transmitted Infections, Guangzhou, China., Lopez-Medina E; Centro Internacional de Entrenamiento e Investigaciones Medicas (CIDEIM), Cali, Colombia.; Centro de Estudios en Infectología Pediátrica (CEIP), Cali, Colombia., Ramirez LG; Centro Internacional de Entrenamiento e Investigaciones Medicas (CIDEIM), Cali, Colombia.; Universidad ICESI, Cali, Colombia., Radolf JD; Department of Medicine, UConn Health, Farmington, CT, United States.; Department of Pediatrics, UConn Health, Farmington, CT, United States.; Department of Molecular Biology and Biophysics, UConn Health, Farmington, CT, United States.; Department of Immunology, UConn Health, Farmington, CT, United States.; Department of Genetics and Genome Sciences, UConn Health, Farmington, CT, United States., Hawley KL; Department of Medicine, UConn Health, Farmington, CT, United States.; Department of Pediatrics, UConn Health, Farmington, CT, United States.; Department of Immunology, UConn Health, Farmington, CT, United States.; Division of Infectious Diseases and Immunology, Connecticut Children's Medical Center, Hartford, CT, United States., Salazar JC; Department of Pediatrics, UConn Health, Farmington, CT, United States.; Department of Immunology, UConn Health, Farmington, CT, United States.; Division of Infectious Diseases and Immunology, Connecticut Children's Medical Center, Hartford, CT, United States., Lukehart SA; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States.; Department of Global Health, University of Washington School of Medicine, Seattle, WA, United States., Seña AC; Division of Infectious Diseases, Institute for Global Health and Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States., Parr JB; Division of Infectious Diseases, Institute for Global Health and Infectious Diseases, The University of North Carolina at Chapel Hill, Chapel Hill, NC, United States., Giacani L; Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, WA, United States.; Department of Global Health, University of Washington School of Medicine, Seattle, WA, United States., Greninger AL; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA, United States.; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in microbiology [Front Microbiol] 2022 Sep 20; Vol. 13, pp. 1007056. Date of Electronic Publication: 2022 Sep 20 (Print Publication: 2022).
DOI:	10.3389/fmicb.2022.1007056
Abstrakt:	Sequencing of most Treponema pallidum genomes excludes repeat regions in tp0470 and the tp0433 gene, encoding the acidic repeat protein ( arp ). As a first step to understanding the evolution and function of these genes and the proteins they encode, we developed a protocol to nanopore sequence tp0470 and arp genes from 212 clinical samples collected from ten countries on six continents. Both tp0470 and arp repeat structures recapitulate the whole genome phylogeny, with subclade-specific patterns emerging. The number of tp0470 repeats is on average appears to be higher in Nichols-like clade strains than in SS14-like clade strains. Consistent with previous studies, we found that 14-repeat arp sequences predominate across both major clades, but the combination and order of repeat type varies among subclades, with many arp sequence variants limited to a single subclade. Although strains that were closely related by whole genome sequencing frequently had the same arp repeat length, this was not always the case. Structural modeling of TP0470 suggested that the eight residue repeats form an extended α-helix, predicted to be periplasmic. Modeling of the ARP revealed a C-terminal sporulation-related repeat (SPOR) domain, predicted to bind denuded peptidoglycan, with repeat regions possibly incorporated into a highly charged β-sheet. Outside of the repeats, all TP0470 and ARP amino acid sequences were identical. Together, our data, along with functional considerations, suggests that both TP0470 and ARP proteins may be involved in T. pallidum cell envelope remodeling and homeostasis, with their highly plastic repeat regions playing as-yet-undetermined roles. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Lieberman, Armstrong, Chung, Pfalmer, Hennelly, Haynes, Romeis, Wang, Zhang, Kou, Ciccarese, Conte, Cusini, Drago, Nakayama, Lee, Ohnishi, Konda, Vargas, Eguiluz, Caceres, Klausner, Mitja, Rompalo, Mulcahy, Hook, Hoffman, Matoga, Zheng, Yang, Lopez-Medina, Ramirez, Radolf, Hawley, Salazar, Lukehart, Seña, Parr, Giacani and Greninger.)
Databáze:	MEDLINE
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