Treponema

Dr. Parag Chauhan

Introduction

  • Treponema species are thin, spiral-shaped bacteria belonging to the family Spirochaetaceae.

  • Among them, Treponema pallidum is the most medically important species and is the causative agent of syphilis.

  • Syphilis is a chronic, systemic sexually transmitted infection with multiple clinical stages and diverse manifestations.

  • Other pathogenic treponemes such as T. pertenue and T. carateum cause non-venereal diseases like yaws and pinta.

  • Treponema species are highly fastidious organisms and cannot be cultured on routine laboratory media.

  • Their unique morphology, motility, and immune evasion mechanisms contribute to persistent infection.

  • Laboratory diagnosis relies mainly on direct microscopy and serological tests.

  • Treponemal infections remain a significant global public health problem, especially in developing countries.

General Character

Genus: Treponema

Taxonomic Classification

  • Genus: Treponema

  • Family: Spirochaetaceae

Medically Important Species

  • Treponema pallidum – Causes syphilis

  • Treponema pertenue – Causes yaws

  • Treponema carateum – Causes pinta

These species are collectively referred to as pathogenic treponemes and are responsible for chronic human infections.

Morphological Characteristics

Gram Staining

  • Treponema species are Gram-negative

  • Due to their extremely thin structure and delicate peptidoglycan layer, they are not easily visualized by routine Gram staining

  • Special techniques such as dark-field microscopy or silver impregnation stains are required

Shape and Arrangement

  • Shape: Spiral-shaped bacteria (spirochetes)

  • Arrangement:

    • Usually present as single organisms

    • Occasionally may appear in small clusters under microscopy

  • Exhibit characteristic corkscrew motility, which aids tissue penetration

Oxygen Requirement

  • Treponema species are anaerobic or microaerophilic

  • They thrive in low-oxygen environments, such as:

    • Subcutaneous tissues

    • Mucous membranes

    • Lymphatic and vascular systems

 

Morphology

Treponema species are delicate, slender, spiral-shaped bacteria belonging to the spirochetes. Their unique morphology plays a crucial role in their motility and pathogenicity.

Size

  • Length: 6–15 µm

  • Diameter: ~0.1–0.2 µm

  • Extremely thin compared to other bacteria

Shape

  • Spiral-shaped (spirochete)

  • Possess tight, regular, and uniform coils

  • Ends are pointed and tapering

Arrangement

  • Usually found as single, free-living organisms

  • Rarely seen in chains or clusters

Cell Structure

  • Gram-negative in nature, but poorly stained with routine Gram stain

  • Cell envelope consists of:

    • Outer membrane with few exposed proteins

    • Thin peptidoglycan layer

    • Cytoplasmic membrane

This unique structure contributes to low antigenicity and immune evasion.

Motility

  • Highly motile with corkscrew or screw-like movement

  • Motility is due to periplasmic flagella (axial filaments) located between the cell wall and outer membrane

  • Enables penetration through viscous media and tissues

Staining Characteristics

  • Not visualized by:

    • Gram stain

    • Ziehl–Neelsen stain

  • Best demonstrated by:

    • Dark-field microscopy

    • Phase-contrast microscopy

    • Silver impregnation methods (Warthin–Starry stain)

    • Direct fluorescent antibody (DFA) tests

Special Morphological Features

  • Fragile organism, easily destroyed by:

    • Heat

    • Drying

    • Disinfectants

  • Does not form spores

  • No capsule

 

Cultural Characteristics

Growth on Artificial Media

  • Treponema pallidum cannot be cultured on routine or artificial laboratory media

  • No growth on:

    • Blood agar

    • Chocolate agar

    • MacConkey agar

  • This is due to:

    • Lack of essential metabolic pathways

    • Dependence on host cells for nutrients

Growth in Experimental Animals

  • Can be maintained only in living tissue

  • Commonly propagated in:

    • Rabbit testes (standard experimental model)

  • Used mainly for:

    • Research purposes

    • Antigen preparation

    • Pathogenesis studies

Oxygen Requirement

  • Anaerobic to microaerophilic

  • Requires low oxygen tension for survival

  • Does not survive well in aerobic laboratory conditions

Temperature and Environmental Sensitivity

  • Optimal survival near 37°C

  • Highly sensitive to:

    • Heat

    • Drying

    • Soap and disinfectants

  • Rapidly loses viability outside the host

Metabolic Characteristics

  • Limited metabolic activity

  • Utilizes host-derived nutrients

  • Does not produce many detectable biochemical reactions

 

Biochemical Reactions

General Biochemical Characteristics

  • Biochemically inert organism

  • Shows minimal enzymatic and metabolic activity

  • Lacks many metabolic pathways necessary for independent survival

  • Highly dependent on host cells for nutrients and energy

Carbohydrate Utilization

  • Does not ferment carbohydrates in standard laboratory tests

  • Energy is obtained mainly from host-derived glucose and amino acids

  • No detectable acid or gas production in routine media

Enzyme Activity

  • Catalase: Negative

  • Oxidase: Negative

  • Urease: Negative

  • Indole: Negative

Routine enzymatic tests are not useful for laboratory identification.

Protein and Amino Acid Metabolism

  • Limited ability to synthesize amino acids

  • Relies on host tissue for:

    • Amino acids

    • Fatty acids

    • Nucleotides

Lipid Metabolism

  • Cannot synthesize fatty acids efficiently

  • Utilizes host lipids for membrane formation

  • Outer membrane has few exposed proteins, contributing to low antigenicity

 

Pathogenicity

Virulence Factors of Treponema Species

1. Surface Proteins (Antigenic Variation)

  • Treponema pallidum possesses variable outer surface proteins

  • Continuous antigenic variation helps the organism:

    • Evade host immune response

    • Establish chronic and persistent infection

  • Low antigen density on the outer membrane delays immune recognition

2. Hyaluronidase

  • Enzyme produced by Treponema pallidum

  • Breaks down hyaluronic acid in connective tissue

  • Facilitates:

    • Tissue invasion

    • Rapid local spread

    • Hematogenous dissemination

Clinical Infections Caused by Treponema Species

1. Treponema pallidum – Syphilis

Syphilis is a chronic systemic disease with multiple clinical stages:

Primary Syphilis

  • Appearance of a painless, indurated chancre at the site of inoculation

  • Regional lymphadenopathy

  • Highly infectious stage

Secondary Syphilis

  • Due to systemic dissemination of organisms

  • Features include:

    • Generalized skin rash (palms and soles)

    • Mucous membrane lesions

    • Condylomata lata

    • Fever, malaise, and lymphadenopathy

Latent Syphilis

  • Asymptomatic phase

  • Serological tests remain positive

  • Divided into:

    • Early latent

    • Late latent

  • Disease may reactivate

Tertiary Syphilis

  • Occurs years after untreated infection

  • Severe complications include:

    • Gummatous lesions

    • Cardiovascular syphilis (aortitis, aneurysm)

    • Neurosyphilis (tabes dorsalis, general paresis)

2. Treponema pertenue – Yaws

  • Non-venereal treponemal infection

  • Transmitted by direct skin contact

  • Common in tropical and subtropical regions

  • Causes:

    • Chronic skin lesions

    • Bone and joint deformities in late stages

3. Treponema carateum – Pinta

  • Non-venereal treponemal disease

  • Primarily affects the skin

  • Characterized by:

    • Papular skin lesions

    • Progressive depigmentation

  • No systemic involvement

 

Laboratory Diagnosis

1. Specimen Collection

  • Exudate from chancre or mucous patches (primary/secondary syphilis)

  • Blood (serum) for serological tests

  • Cerebrospinal fluid (CSF) in suspected neurosyphilis

  • Placental tissue / cord blood in congenital syphilis

2. Direct Demonstration of the Organism

a. Dark-Field Microscopy

  • Specimen: Fresh exudate from chancre

  • Shows:

    • Thin, spiral-shaped, actively motile spirochetes

  • Most useful in early syphilis

  • Not useful for oral lesions (commensal spirochetes)

b. Direct Fluorescent Antibody Test (DFA-TP)

  • Uses fluorescein-labeled antibodies

  • Highly specific

  • Can differentiate pathogenic T. pallidum from non-pathogenic spirochetes

c. Silver Impregnation Staining

  • Warthin–Starry stain

  • Demonstrates spirochetes in tissue sections

  • Used mainly in histopathology

3. Serological Tests

Serology is the mainstay of diagnosis.

A. Non-Treponemal Tests (Screening Tests)

Test Principle Use
VDRL Detects reagin antibodies Screening
RPR Cardiolipin antigen test Screening

Advantages:

  • Inexpensive

  • Useful for monitoring treatment response

Limitations:

  • False positives

  • Less specific

B. Treponemal Tests (Confirmatory Tests)

Test Principle
TPHA Hemagglutination
FTA-ABS Fluorescent antibody test
ELISA Detects treponemal antibodies

Features:

  • Highly specific

  • Remain positive for life

  • Used for confirmation

4. CSF Examination (Neurosyphilis)

  • Elevated protein

  • Increased lymphocytes

  • Positive CSF-VDRL (highly specific)

5. Molecular Methods

  • PCR for detection of T. pallidum DNA

  • Useful in:

    • Early infection

    • Congenital syphilis

  • Limited availability

6. Diagnostic Algorithm 

  1. Screen with VDRL / RPR

  2. Confirm with TPHA / FTA-ABS

  3. Assess disease stage clinically

  4. Monitor therapy with VDRL titers

 

Antibiotic Resistance

Susceptibility Pattern

  • Penicillin G remains the drug of choice for all stages of syphilis

  • No confirmed clinical resistance to penicillin has been documented

  • Treatment failure with penicillin is extremely rare and usually due to:

    • Inadequate dosing

    • Poor patient compliance

    • Reinfection

Resistance to Other Antibiotics

1. Macrolide Resistance

  • Increasing resistance reported to:

    • Azithromycin

    • Erythromycin

  • Resistance due to mutations in 23S rRNA gene

  • Leads to:

    • Treatment failure

    • Reduced usefulness of macrolides as alternative therapy

2. Tetracyclines

  • Doxycycline remains effective

  • Used in:

    • Penicillin-allergic patients

  • No widespread resistance reported, but requires strict compliance

3. Cephalosporins

  • Ceftriaxone shows good activity

  • Used in:

    • Neurosyphilis

    • Penicillin allergy (with caution)

Mechanisms Limiting Resistance Development

  • Lack of plasmids

  • Limited horizontal gene transfer

  • Reduced metabolic activity

  • Obligate dependence on host environment

Laboratory Detection of Resistance

  • Routine antimicrobial susceptibility testing is not feasible

  • Resistance detected by:

    • Molecular methods (PCR) identifying resistance-associated mutations

  • Surveillance studies guide treatment policies

 

Prevention

1. Primary Prevention (Preventing Infection)

Safe Sexual Practices

  • Consistent and correct use of condoms

  • Avoidance of:

    • Multiple sexual partners

    • Unprotected sexual intercourse

  • Sexual health education and awareness programs

Health Education

  • Public education regarding:

    • Modes of transmission

    • Early symptoms of syphilis

  • Promotion of responsible sexual behavior

  • Targeted education for high-risk populations

2. Secondary Prevention (Early Detection and Treatment)

Screening Programs

  • Routine serological screening for:

    • Pregnant women (antenatal screening)

    • Sexually active individuals at high risk

  • Early diagnosis prevents complications and transmission

Prompt Treatment

  • Early treatment with Penicillin G

  • Treatment of:

    • Infected individuals

    • Sexual partners (contact tracing)

3. Prevention of Congenital Syphilis

  • Mandatory antenatal screening during pregnancy

  • Immediate treatment of seropositive pregnant women

  • Follow-up testing of neonates born to infected mothers

4. Public Health Measures

  • Partner notification and treatment

  • Surveillance and reporting of cases

  • Accessible sexually transmitted infection (STI) clinics

  • Integration of syphilis control with HIV prevention programs

5. Infection Control Measures

  • Screening of blood donors

  • Use of sterile needles and syringes

  • Universal precautions in healthcare settings

6. Vaccination

  • No vaccine is currently available for syphilis

  • Prevention relies entirely on:

    • Behavioral modification

    • Screening

    • Early treatment

 

MCQs

1. Treponema pallidum belongs to which family?

A. Enterobacteriaceae
B. Spirochaetaceae
C. Mycobacteriaceae
D. Neisseriaceae
✅ Answer: B

2. The causative agent of syphilis is:

A. Treponema pertenue
B. Treponema carateum
C. Treponema pallidum
D. Borrelia burgdorferi
✅ Answer: C

3. Treponema species are best described as:

A. Gram-positive cocci
B. Gram-negative rods
C. Spiral-shaped spirochetes
D. Curved bacilli
✅ Answer: C

4. Routine Gram staining of Treponema pallidum is difficult because:

A. Thick capsule
B. Lack of cell wall
C. Extremely thin structure
D. Acid-fast nature
✅ Answer: C

5. Best method to visualize T. pallidum in early syphilis:

A. Gram stain
B. Ziehl–Neelsen stain
C. Dark-field microscopy
D. India ink
✅ Answer: C

6. Motility in Treponema pallidum is due to:

A. Polar flagella
B. Pili
C. Axial filaments
D. Cilia
✅ Answer: C

7. Oxygen requirement of Treponema species:

A. Obligate aerobe
B. Facultative anaerobe
C. Obligate anaerobe / microaerophilic
D. Capnophilic
✅ Answer: C

8. Treponema pallidum can be cultured on:

A. Blood agar
B. Chocolate agar
C. Lowenstein–Jensen medium
D. Cannot be cultured artificially
✅ Answer: D

9. Experimental animal used for propagation of T. pallidum:

A. Mouse
B. Guinea pig
C. Rabbit testes
D. Monkey
✅ Answer: C

10. Treponema pallidum is biochemically:

A. Highly active
B. Moderately active
C. Inert
D. Acid fermenter
✅ Answer: C

11. Catalase test for Treponema pallidum is:

A. Positive
B. Weakly positive
C. Variable
D. Negative
✅ Answer: D

12. Enzyme that facilitates tissue invasion in syphilis:

A. Coagulase
B. Hyaluronidase
C. Lecithinase
D. DNase
✅ Answer: B

13. Humans are the _____ host for T. pallidum:

A. Intermediate
B. Accidental
C. Only natural
D. Reservoir and vector
✅ Answer: C

14. Primary syphilitic lesion is called:

A. Gumma
B. Ulcer
C. Chancre
D. Papule
✅ Answer: C

15. Chancre of syphilis is typically:

A. Painful
B. Pus-forming
C. Painless and indurated
D. Necrotic
✅ Answer: C

16. Rash involving palms and soles is seen in:

A. Primary syphilis
B. Secondary syphilis
C. Latent syphilis
D. Tertiary syphilis
✅ Answer: B

17. Condylomata lata occur in:

A. Primary syphilis
B. Secondary syphilis
C. Latent syphilis
D. Congenital syphilis
✅ Answer: B

18. Latent syphilis is characterized by:

A. Severe symptoms
B. Asymptomatic phase
C. CNS involvement
D. Skin gummas
✅ Answer: B

19. Gumma formation occurs in:

A. Primary syphilis
B. Secondary syphilis
C. Latent syphilis
D. Tertiary syphilis
✅ Answer: D

20. Obliterative endarteritis is characteristic of:

A. Tuberculosis
B. Syphilis
C. Leprosy
D. Gonorrhea
✅ Answer: B

21. Non-venereal treponemal disease causing yaws:

A. T. pallidum
B. T. carateum
C. T. pertenue
D. T. denticola
✅ Answer: C

22. Pinta is caused by:

A. T. pallidum
B. T. pertenue
C. T. carateum
D. Borrelia
✅ Answer: C

23. Screening test for syphilis:

A. TPHA
B. FTA-ABS
C. VDRL
D. ELISA only
✅ Answer: C

24. VDRL test detects:

A. Treponemal antibodies
B. Reagin antibodies
C. IgE antibodies
D. Complement proteins
✅ Answer: B

25. Confirmatory test for syphilis:

A. RPR
B. VDRL
C. TPHA
D. ESR
✅ Answer: C

26. Treponemal tests usually remain positive:

A. Only in early disease
B. Until treatment
C. For life
D. For 6 months
✅ Answer: C

27. Best test to monitor treatment response:

A. TPHA
B. FTA-ABS
C. VDRL titer
D. ELISA
✅ Answer: C

28. CSF-VDRL is used to diagnose:

A. Congenital syphilis
B. Primary syphilis
C. Neurosyphilis
D. Latent syphilis
✅ Answer: C

29. Drug of choice for syphilis:

A. Azithromycin
B. Ciprofloxacin
C. Penicillin G
D. Doxycycline
✅ Answer: C

30. Resistance to penicillin in T. pallidum is:

A. Common
B. Increasing
C. Rare but present
D. Not documented
✅ Answer: D

31. Macrolide resistance in T. pallidum is due to mutation in:

A. gyrA gene
B. 16S rRNA
C. 23S rRNA
D. rpoB
✅ Answer: C

32. Alternative drug in penicillin allergy:

A. Metronidazole
B. Doxycycline
C. Amikacin
D. Vancomycin
✅ Answer: B

33. Congenital syphilis occurs due to:

A. Breastfeeding
B. Sexual contact
C. Transplacental transmission
D. Blood transfusion
✅ Answer: C

34. Hutchinson teeth are seen in:

A. Primary syphilis
B. Secondary syphilis
C. Congenital syphilis
D. Latent syphilis
✅ Answer: C

35. Treponema pallidum lacks:

A. Cell wall
B. Capsule
C. Axial filaments
D. Outer membrane
✅ Answer: B

36. Antigenic variation in T. pallidum helps in:

A. Rapid multiplication
B. Immune evasion
C. Antibiotic resistance
D. Sporulation
✅ Answer: B

37. Best prevention of syphilis:

A. Vaccination
B. Antibiotic prophylaxis
C. Safe sexual practices
D. Isolation
✅ Answer: C

38. Vaccine for syphilis is:

A. Available
B. Under trial
C. Partially effective
D. Not available
✅ Answer: D

39. Antenatal screening prevents:

A. Secondary syphilis
B. Neurosyphilis
C. Congenital syphilis
D. Tertiary syphilis
✅ Answer: C

40. Treponema pallidum outer membrane has:

A. Many exposed proteins
B. Lipopolysaccharide
C. Few exposed antigens
D. Thick capsule
✅ Answer: C

41. Dark-field microscopy is NOT useful in:

A. Genital chancre
B. Oral lesions
C. Secondary syphilis
D. Early syphilis
✅ Answer: B

42. Which test may give false-positive results?

A. TPHA
B. FTA-ABS
C. VDRL
D. PCR
✅ Answer: C

43. Mode of transmission of yaws:

A. Sexual
B. Vector-borne
C. Direct skin contact
D. Airborne
✅ Answer: C

44. Pinta mainly affects:

A. CNS
B. Cardiovascular system
C. Skin
D. Bone marrow
✅ Answer: C

45. Treponema pallidum survives poorly outside host due to:

A. Capsule
B. Spores
C. Fragile nature
D. Acid resistance
✅ Answer: C

46. Shape of Treponema pallidum is:

A. Curved comma
B. Straight rod
C. Tight spiral
D. Oval cocci
✅ Answer: C

47. Treponema pallidum energy source is mainly:

A. Fatty acids
B. Host-derived glucose
C. Amino acid fermentation
D. Nitrate reduction
✅ Answer: B

48. Non-treponemal tests detect antibodies against:

A. Flagella
B. Cardiolipin
C. DNA
D. Protein antigens
✅ Answer: B

49. Which stage is most infectious?

A. Latent
B. Tertiary
C. Primary & Secondary
D. Congenital
✅ Answer: C

50. Best public health measure to control syphilis:

A. Mass vaccination
B. Early diagnosis and treatment
C. Vector control
D. Isolation only
✅ Answer: B