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Case Reports
. 2024 Jul 1;51(7):486-492.
doi: 10.1097/OLQ.0000000000001971. Epub 2024 Jun 3.

A Novel Treponema pallidum Subspecies pallidum Strain Associated With a Painful Oral Lesion Is a Member of a Potentially Emerging Nichols-Related Subgroup

Maria Rosa Velasquez  1 , Bridget D De Lay  2 , Diane G Edmondson  2 , Gary P Wormser  1 , Steven J Norris  2 , Kaitlin Cafferky  3 , Eric Munzer  4 , Ciril-Christian Rizk  5 , Marina Keller  1
Affiliations
Case Reports

A Novel Treponema pallidum Subspecies pallidum Strain Associated With a Painful Oral Lesion Is a Member of a Potentially Emerging Nichols-Related Subgroup

Maria Rosa Velasquez et al. Sex Transm Dis. .

Abstract

Background: Early syphilitic lesions are typically painless; however, several recent case studies have included patients with tender lesions and no evidence of concurrent infections. Here we present the manifestations and serological and molecular findings of a patient from New York State with a painful tongue lesion.

Methods: The diagnosis of syphilis was based on a combination of physical examination, serologic, pathologic, and immunohistochemical findings. DNA obtained from a formalin-fixed, paraffin-embedded biopsy was used to characterize the infecting pathogen using polymerase chain reaction, multilocus sequence typing, and whole-genome sequencing methods.

Results: Polymerase chain reaction and multilocus sequence typing of the biopsy specimen confirmed infection with T. pallidum subspecies pallidum ( T. pallidum ) of the Nichols cluster. Whole-genome sequencing analysis of this strain (herein called NYMC01) showed that it contained 17 unique single nucleotide variations and 4 more complex genetic differences; this novel genotype matched only 2 specimens, both from a patient in Seattle, Washington. The presence of this rare genotype in 2 geographically distinct locations suggests the potential emergence and spread of a new subgroup of the Nichols cluster.

Conclusions: To our knowledge, this is the first genomic sequence obtained from a T. pallidum strain linked to a painful lesion, and the third description of whole-genome sequencing of T. pallidum from formalin-fixed, paraffin-embedded tissue. Analysis of additional specimens may reveal that the NYMC01-related genotype represents an emerging T. pallidum subgroup and may also aid in determining whether the painful clinical presentation of primary syphilis is related to specific T. pallidum genotypes.

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Conflict of interest statement

Conflict of Interest and Sources of Funding: The authors declare no conflicts of interest. This research was supported in part by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under award numbers R01 AI141958 (D.G.E., S.J.N.) and R21 AI171714 (D.G.E.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Figures

Figure 1.
Figure 1.. Photography of tongue and lesion before and after seven days of treatment with oral doxycycline.
(A) Before treatment. The area of the biopsy is apparent in the middle of the tongue. (B) After treatment, showing resolution of the lesion.
Figure 2.
Figure 2.. Photomicrograph of the tongue biopsy.
(A) A dense lymphocyte, histiocyte, and reactive plasma cell infiltration was present (Hematoxylin-Eosin). (B) A high prevalence of spirochetes (red) was detected by immunostaining using anti-T. pallidum antiserum with a Giemsa counterstain (blue).
Figure 3.
Figure 3.. Frequencies of genetic differences between the NYMC01 strain and the Nichols (A) and SS14 (B) strains.
(A) A total of 88 genetic differences were observed between genomes of NYMC01 and the Nichols strain. (B) The distribution of 267 differences between NYMC01 and SS14 strains is shown. (C and D) Relatively few differences were found between the NYMC01 genome and the sequences P-22–20198_RA and R-22–10139_RA, derived from pharyngeal and rectal swab specimens of a Seattle patient (18). (E) Only 4 differences were observed between the P-22–20198_RA and R-22–10139_RA. tprK sequence differences related to antigenic variation as well as indeterminant regions (N’s) were excluded from these analyses.
Figure 4.
Figure 4.. Phylogenetic analysis of NYMC01 and T. pallidum strains.
A Genome BLAST Distance Phylogeny (GBDP) tree was created using the Type Strain Genome Server (16, 17). The NYMC01 strain (marked with a red dot) clustered closely with P-22–20198_RA and R-22–10139_RA.
See this image and copyright information in PMC

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