Treponema

Treponema is a gram-negative, microaerophilic spirochete. Owing to its very thin structure, it is not easily seen on Gram stain, but can be visualized using dark-field microscopy. This spirochete contains endoflagella, which allow for a characteristic corkscrew movement. The bacteria are able to avoid immune recognition and phagocytosis by forming a protective coating with fibronectin. Humans are the only reservoir and transmission is through human-to-human contact. The most common species involved in human disease is Treponema pallidum subspecies pallidum, which is the causative agent of syphilis. Other clinically relevant species include T. pallidum pertenue, T. pallidum endemicum, and T. carateum. These are the causative organisms for yaws, bejel, and pinta, respectively.

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Classification

Gram-negative bacteria:
Most bacteria can be classified according to a lab procedure called Gram staining.
Bacteria with cell walls that have a thin layer of peptidoglycan do not retain the crystal violet stain utilized in Gram staining. These bacteria do, however, retain the safranin counterstain and thus appear as pinkish-red on the stain, making them gram negative. These bacteria can be further classified according to morphology (diplococci, curved rods, bacilli, and coccobacilli) and their ability to grow in the presence of oxygen (aerobic versus anaerobic). The bacteria can be more narrowly identified by growing them on specific media (triple sugar iron (TSI) agar) where their enzymes can be identified (urease, oxidase) and their ability to ferment lactose can be tested.
* Stains poorly on Gram stain
** Pleomorphic rod/coccobacillus
*** Require special transport media

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General Characteristics of Treponema

Basic features of Treponema species

  • Spirochete (spiral shaped)
  • Gram negative
  • Microaerophilic
  • Endoflagellated
    • 3 flagella originate from each end.
    • Located in the periplasmic space
  • Classic motility:
    • Rotates rapidly about its longitudinal axis
    • Bends, flexes, and snaps
  • Visualization:
    • Dark-field microscopy
    • Too slender to be visualized using Gram or Giemsa stain
  • Cannot be grown in culture
  • The pathogenic species are morphologically and antigenically indistinguishable.

Clinically relevant species

  • T. pallidum subspecies:
    • T. pallidum subspecies pallidum (syphilis)
    • T. pallidum subspecies endemicum (bejel)
    • T. pallidum subspecies pertenue (yaws)
  • T. carateum (pinta)

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Pathogenesis

Pathogenesis of Treponema infections
The pathogen adheres to the skin or mucosal membranes and leads to the production of hyaluronidase, which allows for tissue invasion. The pathogen coats itself in the host fibronectin, which prevents its phagocytosis and recognition by the immune system. Consequently, the pathogen disseminates through the bloodstream. A host immune response ultimately occurs, which causes disease manifestations.

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Reservoirs and transmission

  • Humans are the only reservoir.
  • Transmission is human-to-human:
    • Sexual contact (syphilis)
    • Vertical (syphilis)
    • Contact with infected lesions (yaws, bejel, and pinta)

Virulence

  • Hyaluronidase
    • Allows tissue invasion
    • Facilitates dissemination
  • Corkscrew motility
    • Able to move in thick substances (e.g., connective tissue)
    • Assists with dissemination
  • Fibronectin
    • Protective coating
    • Comes from the host
    • Prevents phagocytosis and immune recognition

Diseases Caused by Treponema

Syphilis

The most common treponemal disease caused by T. pallidum pallidum:

Table: Syphilis
StagePrimary syphilisSecondary syphilisTertiary syphilisCongenital syphilis
TransmissionSexual contactSkin contact with disseminated rashPatients are not contagious at this stagePlacental, during the first trimester
SymptomsLocalized disease:
  • Painless chancre
  • Painless buboes after chancre resolution
Systemic disease:
  • Maculopapular rash (including palms and soles)
  • Condylomata lata
  • Lymphadenopathy
  • Flu-like symptoms
Systemic disease:
  • Gummas
  • Destructive bone lesions
  • Aortitis
  • Neurogenic arthropathy
Neurosyphilis:
  • Tabes dorsalis
  • Argyll Robertson pupil
  • Meningitis or meningoencephalitis
  • Stroke
  • Saddle nose
  • Hutchinson’s teeth
  • Saber shins
  • CN VIII deafness
  • Rhagades
  • Mulberry molars
  • Nasal discharge
  • Short maxilla
Diagnosis
  • RPR
  • VDRL
  • FTA-ABS
  • Dark-field microscopy
  • MHA-TP
  • PCR of CSF (neurosyphilis)
Management
  • Penicillin G
  • Ceftriaxone
  • Doxycycline
Prevention
  • Safe sex practices
  • Penicillin prophylaxis (if known exposure)
Mothers are tested and treated during pregnancy.

CN: cranial nerve

VDRL: Venereal Disease Research Laboratories test

RPR: rapid plasma reagin test

FTA-ABS: fluorescent treponemal antibody absorption test

MHA-TP: microhemagglutination test

PCR: polymerase chain reaction

CSF: cerebrospinal fluid

Non-venereal diseases

The less-common species of Treponema and their diseases are summarized below:

Table: Less-common species of Treponema and their diseases
DiseaseYawsBejel (endemic syphilis)Pinta
Associated speciesT. pallidum pertenueT. pallidum endemicumT. carateum
Transmission
  • Human-to-human
  • Direct contact with skin lesions
  • Human-to-human
  • Direct contact with mucosal lesions
  • Utensils
  • Human-to-human
  • Direct contact with skin lesions
Predominant locationsTropical regions:
  • Africa
  • South America
  • India
  • Indonesia
  • Pacific Islands
Desert regions:
  • Middle East
  • Central and South Africa
Tropical regions: Central and South America
Primary demographicChildrenChildrenAdults
Clinical manifestationsPrimary phase: painless, yellow papilloma lesion on lower extremities
Secondary phase:
  • Solitary or disseminated papilloma-like skin lesions
  • Palms and soles may be involved.
  • Osteoperiostitis
Tertiary phase:
  • Gummas
  • Destructive bone lesions and skin ulcerations, particularly those of the face
Primary phase: small, primary papule on the oral mucosa
Secondary phase:
  • Plaques on mucous membranes, skin, muscle, and bone
  • Lesions become condylomatous before eventually healing.
  • Periostitis
Tertiary phase:
  • Gummas
  • Destructive bone lesions and skin ulcerations, particularly those of the face
Primary phase:
  • Initial small, red, pruritic papules
  • Commonly on lower extremities
Secondary phase: diffuse, flat skin lesions (pintids)
Tertiary phase:
  • Skin discoloration
  • Depigmentation
  • Atrophy
DiagnosisSince these treponemal species are morphologically indistinguishable, the diagnosis is based on:
  • Clinical manifestations
  • Geographic region
  • Demographics
Supporting evidence:
  • VDRL
  • FTA-ABS
Management
  • Penicillin G
  • Azithromycin

VDRL: Venereal Disease Research Laboratories test

FTA-ABS: fluorescent treponemal antibody absorption test

Comparison of Spirochetes

Spirochetes are gram negative, spiral shaped, and motile. The following table briefly compares some clinically relevant spirochetes:

Table: Comparison of clinically relevant spirochetes
OrganismTreponema pallidum pallidumOther T. pallidum subspeciesTreponema carateumBorrelia burgdorfiBorrelia recurrentisLeptospira interrogans
Micro
  • Microaero
  • Not seen using Gram or Giemsa stain
  • Microaero
  • Not seen using Gram or Giemsa stain
  • Microaero
  • Not seen using Gram or Giemsa stain
  • Microaero
  • Seen using Giemsa and Wright stain
  • Microaero
  • Seen using Giemsa and Wright stain
  • Aerobic
  • Hooked ends
Virulence
  • Hyaluronidase
  • Fibronectin coating
  • Hyaluronidase
  • Fibronectin coating
  • Hyaluronidase
  • Fibronectin coating
  • Antigenic variation
  • Osp regulation
Antigenic variation
  • LPS
  • Hemolysins
  • Complement regulators and enzymes
ReservoirHumansHumansHumans
  • Rodents
  • Deer
Humans
  • Wild animals
  • Livestock
  • Domesticated animals
TransmissionSexual contactP2P contactP2P contactIxodes tickLouseDirect contact with animal tissue or fluids
ClinicalSyphilis
  • Yaws
  • Bejel
PintaLyme diseaseRelapsing fever
  • Leptospirosis
  • Weil’s disease
Diagnosis
  • VDRL
  • FTA-ABS
  • Direct visualization
  • Clinical
  • VDRL
  • FTA-ABS
  • Clinical
  • VDRL
  • FTA-ABS
  • Clinical
  • ELISA
  • Western blot
Blood-smear analysis
  • Blood culture
  • Urine culture
  • ELISA
  • PCR
Management
  • Penicillin G
  • Ceftriaxone
  • Doxycycline
  • Penicillin G
  • Azithromycin
  • Penicillin G
  • Azithromycin
  • Doxycycline
  • Amoxicillin
  • Ceftriaxone
  • Penicillin G
  • Doxycycline
  • Penicillin G
  • Doxycycline

Osp: outer surface protein

LPS: lipopolysaccharide

P2P: person-to-person

Microaero: microaerophilic

VDRL: Venereal Disease Research Laboratory test

FTA-ABS: fluorescent treponemal antibody absorption

ELISA: enzyme-linked immunosorbent assay

PCR: polymerase chain reaction

References

  1. Fine, S.M., and Fine, L.S. (2019). Treponematosis (endemic syphilis, yaws, and pinta). In Brusch, J.L. (Ed.), Medscape. Retrieved January 5, 2021, from https://emedicine.medscape.com/article/230403-overview
  2. Chandrasekar, P.H. (2017). Syphilis. In Bronze, M.S. (Ed.), Medscape. Retrieved January 5, 2020, from https://emedicine.medscape.com/article/229461-overview
  3. Gladwin, M., & Trattler, B. (2008). Clinical microbiology made ridiculously simple (4th edition). Miami: MedMaster.
  4. Radolf, J.D. (1996). Treponema. In: Baron S., (Ed.), Medical Microbiology. (4th edition). Galveston (TX): University of Texas Medical Branch at Galveston. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7716/

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