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
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.
Treponema pallidum spirochetes in a sample using a modified Steiner silver stain
Image: “Treponema pallidum 01” by Dr. Edwin P. Ewing, Jr. License: Public Domain
A tissue sample showing numerous thin, spiral-shaped Treponema carateum.
Image: “2900” by CDC. License: Public Domain
Clinically relevant species
- T. pallidum subspecies:
- T. pallidum subspecies pallidum (syphilis)
- T. pallidum subspecies endemicum (bejel)
- T. pallidum subspecies pertenue (yaws)
- T. carateum (pinta)
Pathogenesis
Pathogenesis of Treponema infections
The pathogen adheres to the skin or mucosal membranes, leading to the production of hyaluronidase which allows for tissue invasion. The pathogen coats itself in the host’s 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.
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:
| Stage | Primary syphilis | Secondary syphilis | Tertiary syphilis | Congenital syphilis |
|---|---|---|---|---|
| Transmission | Sexual contact | Skin contact with disseminated rash | Patients are not contagious at this stage | Placental, during the first trimester |
| Symptoms | Localized disease:
| Systemic disease:
| Systemic disease:
|
|
| Diagnosis |
| |||
| Management |
| |||
| Prevention |
| 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
Primary, painless chancre of syphilis (Treponema pallidum pallidum infection)
Image: “Chancres on the penile shaft due to a primary syphilitic infection caused by Treponema pallidum 6803 lores” by M. Rein. License: Public Domain
Non-venereal diseases
The less-common species of Treponema and their diseases are summarized below:
| Disease | Yaws | Bejel (endemic syphilis) | Pinta |
|---|---|---|---|
| Associated species | T. pallidum pertenue | T. pallidum endemicum | T. carateum |
| Transmission |
|
|
|
| Predominant locations | Tropical regions:
| Desert regions:
| Tropical regions: Central and South America |
| Primary demographic | Children | Children | Adults |
| Clinical manifestations | Primary phase: painless, yellow papilloma lesion on lower extremities Secondary phase:
| Primary phase: small, primary papule on the oral mucosa Secondary phase:
| Primary phase:
Tertiary phase:
|
| Diagnosis | Since these treponemal species are morphologically indistinguishable, the diagnosis is based on:
| ||
| Management |
| ||
VDRL: Venereal Disease Research Laboratories test
FTA-ABS: fluorescent treponemal antibody absorption test
Cutaneous manifestation of yaws
Image: “Yaws treatment” by PLOS. License: CC BY 2.5
(A) A patient with lesions on the face due to Treponema pallidum pertenue
(B) Resolution of the lesions after treatment with penicillin
Cutaneous manifestation of yaws
Image: “Yaws 01” by Dr. Peter Perine. License: Public Domain
Juxta-articular skin lesions and nodules on the elbow resulting from a Treponema pallidum pertenue infection
Mucocutaneous lesions of bejel (endemic syphilis)
Image: “Endemic treponemal diseases” by Marks M, Solomon AW, Mabey DC. License: CC BY 4.0
A: An oral lesion of primary bejel resulting from Treponema pallidum endemicum infection
B: Chronic skin lesion of secondary bejel
Gummatous lesions in late-stage bejel (Treponema pallidum endemicum infection)
Image: “Infiltration of skin due to endemic syphilis” by Alireza Abdolrasouli, Adam Croucher, Yahya Hemmati, and David Mabey. License: Public Domain
Cutaneous lesions of pinta (Treponema carateum infection)
Image: “Endemic treponemal diseases” by Marks M, Solomon AW, Mabey DC. License: CC BY 4.0
(A) Erythematous plaque of early pinta
(B) Skin discoloration of late pinta
Comparison of Spirochetes
Spirochetes are gram negative, spiral shaped, and motile. The following table briefly compares some clinically relevant spirochetes:
| Organism | Treponema pallidum pallidum | Other T. pallidum subspecies | Treponema carateum | Borrelia burgdorfi | Borrelia recurrentis | Leptospira interrogans |
|---|---|---|---|---|---|---|
| Micro |
|
|
|
|
|
|
| Virulence |
|
|
|
| Antigenic variation |
|
| Reservoir | Humans | Humans | Humans |
| Humans |
|
| Transmission | Sexual contact | P2P contact | P2P contact | Ixodes tick | Louse | Direct contact with animal tissue or fluids |
| Clinical | Syphilis |
| Pinta | Lyme disease | Relapsing fever |
|
| Diagnosis |
|
|
|
| Blood-smear analysis |
|
| Management |
|
|
|
|
|
|
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
Visual comparison of spirochetes on electron micrograph: thick spirals of Treponema
Image: “Treponema pallidum” by Dr. David Cox. License: Public Domain
Visual comparison of spirochetes on electron micrograph: Borrelia, which are larger than Treponema
Image: “Lyme disease parasite Borrelia burgdorferi” by Claudia Molins. License: Public Domain
Visual comparison of spirochetes on electron micrograph: hooked ends of Leptospira
Image: “A filtration-based technique for simultaneous SEM and TEM sample preparation for the rapid detection of pathogens” by Beniac DR, Siemens CG, Wright CJ, Booth TF. License: CC BY 3.0, edited by Lecturio.
References
- 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
- Chandrasekar, P.H. (2017). Syphilis. In Bronze, M.S. (Ed.), Medscape. Retrieved January 5, 2020, from https://emedicine.medscape.com/article/229461-overview
- Gladwin, M., & Trattler, B. (2008). Clinical microbiology made ridiculously simple (4th edition). Miami: MedMaster.
- 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/
