Classification
Gram-negative
bacteria
Bacteria
Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases.
Bacteriology: Overview:
Most
bacteria
Bacteria
Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases.
Bacteriology: Overview 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
Bacteria
Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases.
Bacteriology: Overview do, however, retain the safranin counterstain and thus appear as pinkish-red on the stain, making them gram negative. These
bacteria
Bacteria
Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases.
Bacteriology: Overview 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
Bacteria
Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases.
Bacteriology: Overview can be more narrowly identified by growing them on specific media (triple sugar iron (TSI) agar) where their
enzymes
Enzymes
Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body's constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules.
Basics of 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 Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis)
- T. pallidum subspecies endemicum ( bejel Bejel Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and Pinta)
- T. pallidum subspecies pertenue ( yaws Yaws Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and Pinta)
- T. carateum ( pinta Pinta Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and Pinta)
Pathogenesis
Pathogenesis of Treponema infections
The pathogen adheres to the
skin
Skin
The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue.
Structure and Function of 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 Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis)
- Vertical ( syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis)
- Contact with infected lesions ( yaws Yaws Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and Pinta, bejel Bejel Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and Pinta, and pinta Pinta Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and Pinta)
Virulence
- Hyaluronidase
- Allows tissue invasion
- Facilitates dissemination
- Corkscrew motility
- Able to move in thick substances (e.g., connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. 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 Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis | Secondary syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis | Tertiary syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis | Congenital syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis |
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| Transmission | Sexual contact | Skin contact with disseminated rash | Patients are not contagious at this stage | Placental, during the first trimester |
| Symptoms | Localized disease:
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Systemic disease:
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Systemic disease:
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Mothers are tested and treated during pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-HCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care. | ||
CN: cranial nerve
VDRL: Venereal Disease Research Laboratories test
RPR: rapid plasma reagin test
FTA-ABS: fluorescent treponemal antibody absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption test
MHA-TP: microhemagglutination test
PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR): polymerase chain reaction Polymerase chain reaction Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR)
CSF: cerebrospinal fluid
Primary, painless chancre of syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. 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 Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis) | Pinta |
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| Associated species | T. pallidum pertenue | T. pallidum endemicum | T. carateum |
| Transmission |
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| Predominant locations | Tropical regions:
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Desert regions:
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Tropical regions: Central and South America |
| Primary demographic | Children | Children | Adults |
| Clinical manifestations | Primary phase: painless, yellow papilloma lesion on lower extremities Secondary phase:
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Primary phase: small, primary papule on the oral mucosa Secondary phase:
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Primary phase:
Tertiary phase:
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| Diagnosis | Since these treponemal species are morphologically indistinguishable, the diagnosis is based on:
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VDRL: Venereal Disease Research Laboratories test
FTA-ABS: fluorescent treponemal antibody absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption test
Cutaneous manifestation of yaws Yaws Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and Pinta
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 Yaws Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and Pinta
Image: “Yaws 01” by Dr. Peter Perine. License: Public Domain
Juxta-articular skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesions and nodules on the elbow resulting from a Treponema pallidum pertenue infection
Mucocutaneous lesions of bejel Bejel Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and Pinta (endemic syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis)
Image: “Endemic treponemal diseases” by Marks M, Solomon AW, Mabey DC. License: CC BY 4.0
A: An oral lesion of primary bejel Bejel Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and Pinta resulting from Treponema pallidum endemicum infection
B: Chronic skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin lesion of secondary bejel Bejel Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and Pinta
Gummatous lesions in late-stage bejel Bejel Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and Pinta (Treponema pallidum endemicum infection)
Image: “Infiltration of skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Structure and Function of the Skin due to endemic syphilis Syphilis Syphilis is a bacterial infection caused by the spirochete Treponema pallidum pallidum (T. p. pallidum), which is usually spread through sexual contact. Syphilis has 4 clinical stages: primary, secondary, latent, and tertiary. Syphilis” by Alireza Abdolrasouli, Adam Croucher, Yahya Hemmati, and David Mabey. License: Public Domain
Cutaneous lesions of pinta Pinta Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and 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 Pinta Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and Pinta
(B) Skin discoloration of late pinta Pinta Yaws, bejel, and pinta are endemic, nonvenereal treponematoses. The causative organisms are Treponema pallidum pertenue (yaws), T. pallidum endemicum (bejel), and T. carateum (pinta). These treponematoses are generally transmitted by direct skin-to-skin contact with infected skin lesions. Yaws, Bejel, and 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 Borrelia Borrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia burgdorfi | Borrelia Borrelia Borrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia recurrentis | Leptospira Leptospira Leptospira is a spiral or question mark-shaped, gram-negative spirochete with hook-shaped ends. The disease, leptospirosis, is a zoonosis, infecting animals. Rodents are the most important reservoir. Bacteria shed in the urine of rodents and other animals can be transmitted to humans via contaminated water. Leptospira/Leptospirosis interrogans |
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| Reservoir | Humans | Humans | Humans |
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| Transmission | Sexual contact | P2P contact | P2P contact | Ixodes tick | Louse | Direct contact with animal tissue or fluids |
| Clinical | Syphilis |
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Pinta | Lyme disease Lyme disease Lyme disease is a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Lyme Disease | Relapsing fever Relapsing fever Relapsing fever is a vector-borne disease caused by multiple species of the spirochete Borrelia. There are 2 major forms of relapsing fever: tick-borne relapsing fever (caused by multiple species, such as B. hermsii, B. miyamotoi, and B. turicatae) and louse-borne relapsing fever (caused by B. recurrentis). Patients go through recurrent stages of fever, crisis phase, and afebrile periods. Relapsing Fever |
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Osp: outer surface protein
LPS: lipopolysaccharide
P2P: person-to-person
Microaero: microaerophilic
VDRL: Venereal Disease Research Laboratory test
FTA-ABS: fluorescent treponemal antibody absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption
ELISA: enzyme-linked immunosorbent assay
PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR): polymerase chain reaction Polymerase chain reaction Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR)
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 Borrelia Borrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia, which are larger than Treponema
Image: “ Lyme disease Lyme disease Lyme disease is a tick-borne infection caused by the gram-negative spirochete Borrelia burgdorferi. Lyme disease is transmitted by the black-legged Ixodes tick (known as a deer tick), which is only found in specific geographic regions. Patient presentation can vary depending on the stage of the disease and may include a characteristic erythema migrans rash. Lyme Disease parasite Borrelia Borrelia Borrelia are gram-negative microaerophilic spirochetes. Owing to their small size, they are not easily seen on Gram stain but can be visualized using dark-field microscopy, Giemsa, or Wright stain. Spirochetes are motile and move in a characteristic spinning fashion due to axial filaments in the periplasmic space. Borrelia burgdorferi” by Claudia Molins. License: Public Domain
Visual comparison of spirochetes on electron micrograph: hooked ends of Leptospira Leptospira Leptospira is a spiral or question mark-shaped, gram-negative spirochete with hook-shaped ends. The disease, leptospirosis, is a zoonosis, infecting animals. Rodents are the most important reservoir. Bacteria shed in the urine of rodents and other animals can be transmitted to humans via contaminated water. Leptospira/Leptospirosis
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/
