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Article ; Online: Relapsing Fever Caused by Borrelia lonestari after Tick Bite in Alabama, USA.

Vazquez Guillamet, Laia J / Marx, Grace E / Benjamin, William / Pappas, Peter / Lieberman, Nicole A P / Bachiashvili, Kimo / Leal, Sixto / Lieberman, Joshua A

Emerging infectious diseases

2023 Volume 29, Issue 2, Page(s) 441–444

Abstract: We report an immunocompromised patient in Alabama, USA, 75 years of age, with relapsing fevers and pancytopenia who had spirochetemia after a tick bite. We identified Borrelia lonestari by using PCR, sequencing, and phylogenetic analysis. Increasing ... ...

Abstract	We report an immunocompromised patient in Alabama, USA, 75 years of age, with relapsing fevers and pancytopenia who had spirochetemia after a tick bite. We identified Borrelia lonestari by using PCR, sequencing, and phylogenetic analysis. Increasing clinical availability of molecular diagnostics might identify B. lonestari as an emerging tickborne pathogen.
MeSH term(s)	Humans ; Relapsing Fever/diagnosis ; Alabama/epidemiology ; Tick Bites/complications ; Phylogeny ; Borrelia/genetics
Language	English
Publishing date	2023-01-24
Publishing country	United States
Document type	Letter
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2902.221281
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Article ; Online: Genomic Analysis of Early Monkeypox Virus Outbreak Strains, Washington, USA.

Roychoudhury, Pavitra / Sereewit, Jaydee / Xie, Hong / Nunley, Ethan / Bakhash, Shah M / Lieberman, Nicole A P / Greninger, Alexander L

Emerging infectious diseases

2023 Volume 29, Issue 3, Page(s) 644–646

Abstract: We conducted a genomic analysis of monkeypox virus sequences collected early in the 2022 outbreak, during July-August , in Washington, USA. Using 109 viral genomes, we found low overall genetic diversity, multiple introductions into the state, ongoing ... ...

Abstract	We conducted a genomic analysis of monkeypox virus sequences collected early in the 2022 outbreak, during July-August , in Washington, USA. Using 109 viral genomes, we found low overall genetic diversity, multiple introductions into the state, ongoing community transmission, and potential for co-infections by multiple strains.
MeSH term(s)	Humans ; Monkeypox virus/genetics ; Mpox (monkeypox)/epidemiology ; Washington ; Genomics ; Disease Outbreaks
Language	English
Publishing date	2023-02-02
Publishing country	United States
Document type	Letter
ZDB-ID	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2903.221446
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Article ; Online: Clinical Performance and Trends during the First Two Months of Monkeypox Virus PCR Testing at Two United States Reference Labs.

Lieberman, Nicole A P / Mathias, Patrick C / Bradley, Benjamin T / Greninger, Alexander L

Journal of clinical microbiology

2022 Volume 60, Issue 12, Page(s) e0137122

Abstract: Recently, a sustained human-to-human outbreak of monkeypox virus (MPXV), a member of ... ...

Abstract	Recently, a sustained human-to-human outbreak of monkeypox virus (MPXV), a member of the
MeSH term(s)	Male ; Humans ; United States/epidemiology ; Middle Aged ; Adult ; Monkeypox virus/genetics ; Mpox (monkeypox)/diagnosis ; Mpox (monkeypox)/epidemiology ; Mpox (monkeypox)/drug therapy ; Polymerase Chain Reaction/methods ; Disease Outbreaks ; Viral Load
Language	English
Publishing date	2022-11-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	390499-4
ISSN	1098-660X ; 0095-1137
ISSN (online)	1098-660X
ISSN	0095-1137
DOI	10.1128/jcm.01371-22
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Article ; Online: Whole Genome Sequence of a Treponema pallidum Strain From a Formalin-Fixed, Paraffin-Embedded Fine Needle Aspirate of a Cervical Lymph Node.

Aldrete, Sol / Kroft, Steven H / Romeis, Emily / Lieberman, Nicole A P / Greninger, Alexander L / Giacani, Lorenzo / Kron, Michael A

Sexually transmitted diseases

2023 Volume 50, Issue 8, Page(s) 550–552

Abstract: Abstract: A patient with unilateral cervical lymphadenopathy suspicious for malignancy underwent a fine needle aspiration. Histology demonstrated mixed inflammatory infiltrates with abundant spirochetes. Sufficient spirochete DNA was extracted from ... ...

Abstract	Abstract: A patient with unilateral cervical lymphadenopathy suspicious for malignancy underwent a fine needle aspiration. Histology demonstrated mixed inflammatory infiltrates with abundant spirochetes. Sufficient spirochete DNA was extracted from paraffin-embedded tissue sections to obtain the near-complete genome sequence of a macrolide-resistant strain belonging to the SS14 omega strain of Treponema pallidum .
MeSH term(s)	Humans ; Treponema pallidum/genetics ; Biopsy, Fine-Needle ; Paraffin Embedding ; Lymph Nodes ; Formaldehyde
Chemical Substances	Formaldehyde (1HG84L3525)
Language	English
Publishing date	2023-05-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	435191-5
ISSN	1537-4521 ; 0148-5717
ISSN (online)	1537-4521
ISSN	0148-5717
DOI	10.1097/OLQ.0000000000001827
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Article: Treponema pallidum

Romeis, Emily / Lieberman, Nicole A P / Molini, Barbara / Tantalo, Lauren C / Chung, Benjamin / Phung, Quynh / Avendaño, Carlos / Vorobieva, Anastassia / Greninger, Alexander L / Giacani, Lorenzo

bioRxiv : the preprint server for biology

2023

Abstract: Background: The TprK protein of the syphilis agent, : Principal findings: A suicide vector was transformed into the wild-type (WT) SS14 : Conclusion: These data further support the critical role of TprK in : Author summary: Syphilis is still ... ...

Abstract	Background: The TprK protein of the syphilis agent, Principal findings: A suicide vector was transformed into the wild-type (WT) SS14 Conclusion: These data further support the critical role of TprK in Author summary: Syphilis is still endemic in low- and middle-income countries, and it has been resurgent in high-income nations, including the U.S., for years. In endemic areas, there is still significant morbidity and mortality associated with this disease, particularly when its causative agent, the spirochete
Language	English
Publishing date	2023-02-23
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.01.18.524629
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Article ; Online: Immunotherapy for brain tumors: understanding early successes and limitations.

Lieberman, Nicole A P / Vitanza, Nicholas A / Crane, Courtney A

Expert review of neurotherapeutics

2018 Volume 18, Issue 3, Page(s) 251–259

Abstract: Introduction: Adverse effects and toxicities related to standard treatments for brain tumors significantly reduce patients' quality of life. Although most immunotherapy approaches for solid tumors have not been successful, several early-phase clinical ... ...

Abstract	Introduction: Adverse effects and toxicities related to standard treatments for brain tumors significantly reduce patients' quality of life. Although most immunotherapy approaches for solid tumors have not been successful, several early-phase clinical trials are beginning to reveal a potential role for immunotherapy in the treatment of brain tumors. In particular, methods that activate the innate immune system and induce a polyclonal anti-cancer response have demonstrated that brain tumors are susceptible to immune-mediated tumor destruction. Compared with conventional therapies, modulation of the immune system may improve both survivorship and quality of life during and following treatment. Areas covered: An overview of mechanisms of immunotherapy in the context of current treatments for adult and pediatric brain tumors is provided. Results from recent clinical trials will be discussed, focusing on the favorable safety and efficacy profiles of immunotherapeutics. Expert commentary: Although it is too early to judge the long-term safety of immunotherapy for the treatment of patients with brain tumors, early results suggest that these drugs are well-tolerated and may improve survival and quality of life. Importantly, approaches that activate an anti-tumor immune response lay the framework for iterative development of immunotherapies that can reliably treat patients with brain tumors.
MeSH term(s)	Brain Neoplasms/immunology ; Brain Neoplasms/therapy ; Combined Modality Therapy ; Humans ; Immunity, Innate ; Immunotherapy/adverse effects ; Immunotherapy/methods ; Quality of Life
Language	English
Publishing date	2018-01-11
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2112534-X
ISSN	1744-8360 ; 1473-7175
ISSN (online)	1744-8360
ISSN	1473-7175
DOI	10.1080/14737175.2018.1425617
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Article: Treponema pallidum

bioRxiv : the preprint server for biology

2024

Abstract: Background: Histologic and serologic studies suggest the induction of local and systemic : Methods: PBMC collected from 67 participants were screened by IFNγ ELISPOT response to : Results: We detected CD4+ T cell responses to : Conclusions: ... ...

Abstract	Background: Histologic and serologic studies suggest the induction of local and systemic Methods: PBMC collected from 67 participants were screened by IFNγ ELISPOT response to Results: We detected CD4+ T cell responses to Conclusions: Tp
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2024.02.27.581790
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Article ; Online: Prevalence and Predictors of Oral Treponema pallidum Detection by qPCR in Early Syphilis.

Dionne, Jodie A / Giacani, Lorenzo / Tamhane, Ashutosh / Workowski, Kimberly / Lieberman, Nicole A P / Greninger, Alexander L / Perlowski, Charlotte / Newman, Lori / Hook, Edward W

The Journal of infectious diseases

2023

Abstract: Background: Treponema pallidum (T. pallidum) prevalence and burden at oral and lesion sites in adults with early syphilis were assessed by qPCR. Factors associated with oral shedding were also examined.: Methods: Pre-treatment oral and lesion swabs ... ...

Abstract	Background: Treponema pallidum (T. pallidum) prevalence and burden at oral and lesion sites in adults with early syphilis were assessed by qPCR. Factors associated with oral shedding were also examined. Methods: Pre-treatment oral and lesion swabs were collected from adults with early syphilis in a US multicenter syphilis treatment trial. Oral swabs were collected in the presence and absence of oral lesions. Following DNA extraction, qPCR and whole genome sequencing (WGS) were performed to assess burden and strain variability. Results: All 32 participants were male, mean age was 35, and 90.6% were living with HIV. T. pallidum oral PCR positivity varied by stage: 16.7% primary, 44.4% secondary, and 62.5% in early latent syphilis. Median oral T. pallidum burden was highest in secondary syphilis at 63.2 copies/µL. Lesion PCR positivity was similar in primary (40.0%) and secondary syphilis (38.5%). Age 18-29 years was significantly associated with oral shedding (vs age 40+) in adjusted models. WGS identified two distinct strains. Conclusion: T. pallidum DNA was directly detected at oral and lesion sites in a high proportion of men with early syphilis. Younger age was associated with oral shedding. Ease of oral specimen collection and increased PCR availability suggest opportunities to improve syphilis diagnostic testing.
Language	English
Publishing date	2023-12-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad582
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Article ; Online: Genomic Epidemiology of Treponema pallidum and Circulation of Strains With Diminished tprK Antigen Variation Capability in Seattle, 2021-2022.

Lieberman, Nicole A P / Avendaño, Carlos C / Bakhash, Shah A K Mohamed / Nunley, Ethan / Xie, Hong / Giacani, Lorenzo / Berzkalns, Anna / Soge, Olusegun O / Reid, Tara B / Golden, Matthew R / Greninger, Alexander L

The Journal of infectious diseases

2023 Volume 229, Issue 3, Page(s) 866–875

Abstract: Background: The incidence of syphilis continues to increase in the United States, yet little is known about Treponema pallidum genomic epidemiology within American metropolitan areas.: Methods: We performed whole-genome sequencing and tprK deep ... ...

Abstract	Background: The incidence of syphilis continues to increase in the United States, yet little is known about Treponema pallidum genomic epidemiology within American metropolitan areas. Methods: We performed whole-genome sequencing and tprK deep sequencing of 28 T. pallidum-containing specimens, collected mostly from remnant Aptima swab specimens from 24 individuals from Seattle Sexual Health Clinic during 2021-2022. Results: All 12 individuals infected with Nichols-lineage strains were men who have sex with men, while a specific SS14 cluster (mean, 0.33 single-nucleotide variant) included 1 man who has sex with women and 5 women. All T. pallidum strains sequenced were azithromycin resistant via 23S ribosomal RNA A2058G mutation. Identical T. pallidum genomic sequences were found in pharyngeal and rectal swab specimens taken concurrently from the same individuals. The tprK sequences were less variable between patient-matched specimens and between epidemiologically linked clusters. We detected a 528-base pair deletion in the tprK donor site locus, eliminating 9 donor sites, in T. pallidum genomes of 3 individuals with secondary syphilis, associated with diminution of TprK diversity. Conclusions: We developed an end-to-end workflow for public health genomic surveillance of T. pallidum from remnant Aptima swab specimens. tprK sequencing may assist in linking cases beyond routine T. pallidum genome sequencing. T. pallidum strains with deletions in tprK donor sites currently circulate and are associated with diminished TprK antigenic diversity.
MeSH term(s)	Male ; Female ; Humans ; Treponema pallidum/genetics ; Homosexuality, Male ; Amino Acid Sequence ; Sexual and Gender Minorities ; Syphilis/epidemiology ; Antigenic Variation ; Genomics
Language	English
Publishing date	2023-09-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiad368
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Article ; Online: Treponema pallidum subsp. pallidum with an Artificially impaired TprK antigenic variation system is attenuated in the Rabbit model of syphilis.

Romeis, Emily / Lieberman, Nicole A P / Molini, Barbara / Tantalo, Lauren C / Chung, Benjamin / Phung, Quynh / Avendaño, Carlos / Vorobieva, Anastassia / Greninger, Alexander L / Giacani, Lorenzo

PLoS pathogens

2023 Volume 19, Issue 3, Page(s) e1011259

Abstract: Background: The TprK protein of the syphilis agent, Treponema pallidum subsp. pallidum (T. pallidum), undergoes antigenic variation in seven discrete variable (V) regions via non-reciprocal segmental gene conversion. These recombination events transfer ... ...

Abstract	Background: The TprK protein of the syphilis agent, Treponema pallidum subsp. pallidum (T. pallidum), undergoes antigenic variation in seven discrete variable (V) regions via non-reciprocal segmental gene conversion. These recombination events transfer information from a repertoire of 53 silent chromosomal donor cassettes (DCs) into the single tprK expression site to continually generate TprK variants. Several lines of research developed over the last two decades support the theory that this mechanism is central to T. pallidum's ability for immune avoidance and persistence in the host. Structural and modeling data, for example, identify TprK as an integral outer membrane porin with the V regions exposed on the pathogen's surface. Furthermore, infection-induced antibodies preferentially target the V regions rather than the predicted β-barrel scaffolding, and sequence variation abrogates the binding of antibodies elicited by antigenically different V regions. Here, we engineered a T. pallidum strain to impair its ability to vary TprK and assessed its virulence in the rabbit model of syphilis. Principal findings: A suicide vector was transformed into the wild-type (WT) SS14 T. pallidum isolate to eliminate 96% of its tprK DCs. The resulting SS14-DCKO strain exhibited an in vitro growth rate identical to the untransformed strain, supporting that the elimination of the DCs did not affect strain viability in absence of immune pressure. In rabbits injected intradermally with the SS14-DCKO strain, generation of new TprK sequences was impaired, and the animals developed attenuated lesions with a significantly reduced treponemal burden compared to control animals. During infection, clearance of V region variants originally in the inoculum mirrored the generation of antibodies to these variants, although no new variants were generated in the SS14-DCKO strain to overcome immune pressure. Naïve rabbits that received lymph node extracts from animals infected with the SS14-DCKO strain remained uninfected. Conclusion: These data further support the critical role of TprK in T. pallidum virulence and persistence during infection.
MeSH term(s)	Animals ; Rabbits ; Syphilis ; Treponema pallidum ; Treponema ; Antigenic Variation/genetics ; Antibodies
Chemical Substances	Antibodies
Language	English
Publishing date	2023-03-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2205412-1
ISSN	1553-7374 ; 1553-7374
ISSN (online)	1553-7374
ISSN	1553-7374
DOI	10.1371/journal.ppat.1011259
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