(P391) Genomic analysis of global Treponema pallidum subs. pallidum strains shows significant allelic differences between Nichols and SS14 lineages

Wednesday, July 26, 2023

16:00 – 18:00 CST

Primary Presenter(s)

Farhang Aghakhanian Fereydani, PhD

Post-Doc Research Associate
Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA, United States

Co-author(s)

PP

Petra Pospíšilová

Masaryk University, Brno, Czech Republic, United States
CH

Chris M. Hennelly

Institute for Global Health and Infectious Diseases, Chapel Hill, North Carolina, USA
Chapel Hill, North Carolina, United States
Kelly L. Hawley, PhD (she/her/hers)

Senior Research Scientist | Assistant Professor
Connecticut Childern's | UConn Health
Farmington, Connecticut, United States
TD

Timothy Davenport

UConn Health, Farmington, Connecticut, USA, United States
Arlene C. Seña, MD, MPH

Professor of Medicine
Department of Medicine, Division of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Chapel Hill, North Carolina, United States
WC

Wentao Chen

Dermatology Hospital, Southern Medical University, Guangzhou, China, Guangdong, China (People's Republic)
YJ

Yinbo Jiang

Dermatology Hospital, Southern Medical University, Guangzhou, China, United States
BY

Bin Yang

Dermatology Hospital, Southern Medical University, Guangzhou, 510091, P. R. China, United States
LY

Ligang Yang

Department of STD Clinic, Dermatology Hospital of Southern Medical University, United States
RC

Rongyi Chen

Dermatology Hospital, Southern Medical University, Guangzhou, China, United States
HZ

Heping Zheng

Dermatology Hospital, Southern Medical University, Guangzhou, China, United States
MM

Mitch M. Matoga, MD, MSc (he/him/his)

Director of STI Research and Clinical Services
University of North Carolina Project Malawi, Lilongwe, Malawi
Lilongwe, Lilongwe, Malawi
IH

Irving Hoffman, MPH

Professor of Medicine
Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Chapel Hill, North Carolina, United States
EL

Eduardo Lopez

CIDEIM, Cali, Colombia, United States
Lady Giovanna Ramírez

Research Assistant
CIDEIM, Cali, Colombia
Cali, Valle del Cauca, Colombia
MC

Melissa J Caimano

Centro Internacional de Entrenamiento e Investigaciones Médicas (CIDEIM), Cali, Colombia; Department of Pediatrics, University of Connecticut School of Medicine, Farmington CT, USA; Department of Medicine, University of Connecticut School of Medicine, Farmington CT, USA, United States
JS

Juan Salazar

UConn Health, Farmington, Connecticut, USA; Connecticut Children’s, Hartford, Connecticut, USA, United States
M. Anthony Moody, MD

Professor of Pediatrics and Immunology
Duke Human Vaccine Institute, Duke Univerity, Durham, North Carolina, USA
Durham, North Carolina, United States
JR

Justin D. Radolf

UConn Health, Farmington, Connecticut, USA; Connecticut Children’s, Hartford, Connecticut, USA; CIDEIM, Cali, Colombia, United States
JJ

Jonathan J. Juliano

Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA, United States
D�

David Šmajs

Masaryk University, Brno, Czech Republic, United States
JP

Jonathan B. Parr, MD, MPH

Assistant Professor of Medicine
Institute for Global Health and Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
Chapel Hill, North Carolina, United States

Background: Deciphering the genetic diversity of Treponema pallidum subsp. pallidum (TPA) is crucial to understanding TPA biology. The growing number of TPA whole genomic sequences (WGS) provides opportunities to study TPA at a global population level. We aimed to evaluate TPA population structure by sequencing clinical samples from syphilis patients from sites across four continents and comparing them with publicly available TPA sequences.

Methods: We sequenced 158 clinical isolates from subjects with early syphilis from Malawi, Colombia, China and the US. Genomic data was analyzed alongside 1255 publicly available TPA genomes to study population structure. We used principal component analysis (PCA) to explore genetic diversity within the global TPA population and identified significantly differentiated SNVs using Fisher’s exact test.

Results: Analysis of 1413 total genomes using PCA confirmed that most genetic variation (51.4%) is explained by membership in the SS14 versus Nichols clades. In our recombination-masked analysis, 103 SNVs were fixed in Nichols or SS14 lineages, and another 169 SNVs significantly differentiated between the two lineages (Bonferroni-corrected Fisher’s exact p < 4.451x10^-6). 26% of significantly differentiated non-synonymous SNVs were in TPA outer membrane proteins (OMPs), especially an accumulation of non-synonymous SNVs in genes belong to the FadL family (TP0865 and TP0858) and TolC homologue TP0966. We also observed significantly differentiated SNVs in TP0462 (including 21 non-synonymous SNVs), a putative lipoprotein gene, and differences in allele frequency patterns associated with TPA lineage and geographical location. We found a high frequency TroR c.314A >G (p.Glu105Gly) mutation in SS14-lineage strains collected from Africa. TroR is a member of the Tro operon, and the mutation could represent an adaptation to low zinc, iron, and/or manganese among participants in Africa. Other SNVs with potential relevance to TPA genetic population structure and biology were identified.

Conclusion:

WGS from geographically diverse sites allowed us to explore TPA genetic diversity and population structure. Investigation of the impact of SNVs driving TPA differentiation on protein structures will provide further insight into their role in TPA biology and evolution and syphilis pathogenesis and can inform the design of a globally effective syphilis vaccine.