Neisseria

Dr. Parag Chauhan

Introduction

  • Neisseria is a genus of Gram-negative, aerobic diplococci that are exclusively human pathogens.

  • Most species are commensals of the upper respiratory tract, but some are highly pathogenic.

  • The two most important pathogenic species are:

    • Neisseria gonorrhoeae – causes gonorrhoea

    • Neisseria meningitidis – causes bacterial meningitis and meningococcemia

  • Pathogenicity is due to pili, outer membrane proteins, IgA protease, and endotoxin (LOS).

  • N. meningitidis possesses a polysaccharide capsule, a major virulence factor.

  • Infections can range from localized mucosal disease to life-threatening systemic infections.

  • Antimicrobial resistance, especially in N. gonorrhoeae, is a growing global concern.

  • Early laboratory diagnosis, appropriate antibiotic therapy, vaccination (for meningococcal disease), and public health measures are essential for prevention and control.

 

General Character

Genus: Neisseria

Family

  • Neisseriaceae

Key Pathogenic Species

  • Neisseria gonorrhoeae – causes gonorrhoea

  • Neisseria meningitidis – causes bacterial meningitis and meningococcemia

Morphological Characteristics

Gram Staining

  • Gram-negative bacteria

  • Appear pink on Gram stain

  • Due to:

    • Thin peptidoglycan layer

    • Presence of an outer membrane

Shape and Arrangement

  • Shape: Diplococci (kidney- or coffee-bean shaped)

  • Arrangement:

    • Typically found in pairs (diplococci)

    • Occasionally seen in short chains

  • In clinical specimens, often found intracellularly within neutrophils (especially N. gonorrhoeae)

Oxygen Requirements

  • Strictly aerobic

  • Require enriched media and special growth conditions for optimal growth

  • Grow best at:

    • 35–37°C

    • 5–10% CO₂ atmosphere

 

Morphology

  • Gram reaction:

    • Gram-negative bacteria

    • Appear pink on Gram staining due to thin peptidoglycan layer and outer membrane

  • Shape:

    • Diplococci

    • Characteristic kidney-shaped / coffee-bean–shaped cocci

  • Arrangement:

    • Usually found in pairs (diplococci) with adjacent sides flattened

    • May be seen in short chains

    • Frequently observed intracellularly within polymorphonuclear leukocytes (PMNs), especially N. gonorrhoeae

  • Size:

    • Approximately 0.6–1.0 µm in diameter

  • Motility:

    • Non-motile

  • Spore formation:

    • Non-spore forming

  • Capsule:

    • Present in Neisseria meningitidis (important virulence factor)

    • Absent in Neisseria gonorrhoeae

  • Cell wall structure:

    • Thin peptidoglycan layer

    • Outer membrane containing lipooligosaccharide (LOS)

 

Cultural Characteristics

  • Growth nature:
    • Fastidious organisms
    • Require enriched media for growth
  • Culture media:
    • Chocolate agar – supports growth of all pathogenic Neisseria
    • Thayer–Martin medium (selective medium)
      • Contains antibiotics (Vancomycin, Colistin, Nystatin, Trimethoprim)
      • Inhibits contaminating flora and allows selective growth of Neisseria
  • Atmospheric requirements:
    • Aerobic
    • Require 5–10% CO₂ (capnophilic) for optimal growth
  • Temperature:
    • Optimal growth at 35–37°C
  • Colony characteristics:
    • Small, round, smooth, moist, translucent colonies
    • Colonies are non-pigmented and non-hemolytic
    • N. gonorrhoeae colonies are delicate and may autolyse rapidly
  • Growth characteristics of key species:
    • Neisseria gonorrhoeae:
      • More fragile, sensitive to drying and temperature changes
    • Neisseria meningitidis:
      • More robust, grows better on routine enriched media
  • Survival:
    • Poor survival outside the human host
    • Sensitive to heat, drying, and disinfectants

 

Biochemical Reactions

Biochemical Reactions of Genus Neisseria

  • Oxidase test:

    • Positive

    • Presence of cytochrome oxidase enzyme

    • Produces purple color within 10 seconds

  • Catalase test:

    • Positive

    • Breaks hydrogen peroxide into water and oxygen

  • Carbohydrate utilization (Sugar fermentation test):

    • Acid production without gas

    • Important for species identification

Species Glucose Maltose Sucrose Lactose
Neisseria gonorrhoeae + – – –
Neisseria meningitidis + + – –
Non-pathogenic Neisseria Variable Variable Variable Variable

  • Nitrate reduction:

    • Negative

  • Indole test:

    • Negative

  • Urease test:

    • Negative

  • Polysaccharide utilization:

    • N. meningitidis utilizes maltose, helping in differentiation

  • Autolysis:

    • Some strains (especially N. gonorrhoeae) show autolysis on prolonged incubation

 

Pathogenicity

Virulence Factors 

  • Pili (fimbriae):

    • Mediate attachment to mucosal epithelial cells

    • Show antigenic variation, helping in immune evasion

    • Essential for colonization

  • Outer membrane proteins (OMP):

    • Aid in adhesion and invasion

    • Prevent complement-mediated killing

  • Lipooligosaccharide (LOS):

    • Acts as endotoxin

    • Causes intense inflammatory response

    • Responsible for tissue damage and septic shock

  • IgA protease:

    • Cleaves secretory IgA

    • Facilitates survival on mucosal surfaces

Pathogenicity of Neisseria gonorrhoeae

  • Mode of transmission:

    • Sexual contact

    • Perinatal transmission (during childbirth)

  • Pathogenesis:

    • Adheres to mucosal epithelium of:

      • Urethra (male)

      • Cervix (female)

      • Rectum, pharynx, conjunctiva

    • Penetrates epithelial cells → induces acute suppurative inflammation

    • Survives intracellularly in neutrophils

  • Clinical manifestations:

    • Urethritis with purulent discharge

    • Cervicitis (often asymptomatic in females)

    • Pelvic inflammatory disease (PID)

    • Infertility and ectopic pregnancy

    • Neonatal conjunctivitis (ophthalmia neonatorum)

    • Disseminated gonococcal infection (arthritis, dermatitis, endocarditis)

Pathogenicity of Neisseria meningitidis

  • Mode of transmission:

    • Respiratory droplets

  • Capsule:

    • Major virulence factor

    • Anti-phagocytic

    • Helps survival in bloodstream

  • Pathogenesis:

    • Colonizes nasopharynx

    • Enters bloodstream → bacteremia

    • Crosses blood–brain barrier → meningitis

  • Clinical manifestations:

    • Acute bacterial meningitis

    • Meningococcemia

    • Petechial or purpuric rash

    • Septic shock

    • Waterhouse–Friderichsen syndrome (adrenal hemorrhage)

 

Laboratory Diagnosis

1. Specimen Collection

Neisseria gonorrhoeae

  • Urethral swab (male)

  • Endocervical swab (female)

  • Rectal and pharyngeal swabs

  • Conjunctival swab (neonates)

  • First-catch urine (for NAAT)

Neisseria meningitidis

  • Cerebrospinal fluid (CSF)

  • Blood (during septicemia)

  • Nasopharyngeal swab (carrier detection)

2. Direct Microscopy

  • Gram staining:

    • Gram-negative, kidney-shaped intracellular diplococci

    • Highly diagnostic in symptomatic males with gonorrhea

    • Lower sensitivity in females and asymptomatic cases

3. Culture

  • Media used:

    • Chocolate agar

    • Thayer–Martin selective medium

  • Incubation conditions:

    • 35–37°C

    • 5–10% CO₂ atmosphere

  • Colony morphology:

    • Small, smooth, moist, translucent colonies

    • N. gonorrhoeae colonies are delicate and may autolyse

4. Biochemical Identification

  • Oxidase test: Positive

  • Catalase test: Positive

  • Carbohydrate fermentation tests:

    • N. gonorrhoeae → Glucose only

    • N. meningitidis → Glucose + Maltose

5. Rapid and Molecular Methods

  • NAAT (Nucleic Acid Amplification Tests):

    • Gold standard for diagnosis of gonorrhea

    • High sensitivity and specificity

    • Useful for urine and non-invasive samples

  • PCR:

    • Rapid identification of meningococcal infection

6. Antigen Detection

  • Latex agglutination test:

    • Detects capsular antigen in CSF

    • Useful in partially treated meningitis cases

7. Serological Tests

  • Limited diagnostic role

  • Mainly used for epidemiological studies

8. Antibiotic Susceptibility Testing

  • Essential due to rising resistance in N. gonorrhoeae

  • Methods:

    • Disk diffusion

    • MIC determination

 

Antibiotic Resistance

1. Neisseria gonorrhoeae – Antibiotic Resistance

Drugs with Documented Resistance

  • Penicillin

    • Due to β-lactamase (penicillinase) production

  • Tetracyclines

  • Fluoroquinolones (e.g., ciprofloxacin)

  • Macrolides (azithromycin – increasing resistance)

  • Reduced susceptibility to third-generation cephalosporins

Mechanisms of Resistance

  • β-lactamase production

    • Plasmid-mediated (penicillin resistance)

  • Altered penicillin-binding proteins (PBPs)

  • Efflux pump overexpression

    • Decreases intracellular antibiotic concentration

  • Porin mutations

    • Reduced drug entry

  • Target site modification

    • Especially for fluoroquinolones and macrolides

Current Recommended Therapy

  • Ceftriaxone (drug of choice)

  • Often used in dual therapy to delay resistance

  • Continuous surveillance is essential

2. Neisseria meningitidis – Antibiotic Resistance

  • Generally less resistant than N. gonorrhoeae

  • Reduced susceptibility reported for:

    • Penicillin

    • Ampicillin

  • Resistance mechanisms:

    • Altered PBPs

  • Most strains remain sensitive to:

    • Ceftriaxone

    • Chloramphenicol (alternative in some settings)

3. Public Health Importance

  • Rapid emergence of multidrug-resistant gonococci

  • Limited treatment options available

  • Emphasis on:

    • Antibiotic stewardship

    • Surveillance programs

    • Early diagnosis and complete treatment

    • Safe sexual practices

 

Prevention

1. Vaccination

Neisseria meningitidis

  • Highly effective vaccines available

  • Types of vaccines:

    • Polysaccharide vaccines

    • Conjugate vaccines (preferred)

    • Recombinant protein vaccines (for serogroup B)

  • Targeted against common serogroups: A, C, Y, W, B

  • Recommended for:

    • Children and adolescents

    • Travelers to endemic areas

    • Military personnel

    • Immunocompromised individuals

Neisseria gonorrhoeae

  • No licensed vaccine available

  • Antigenic variation and lack of protective immunity hinder vaccine development

2. Chemoprophylaxis

Meningococcal Disease

  • Given to close contacts of confirmed cases

  • Drugs used:

    • Rifampicin

    • Ciprofloxacin

    • Ceftriaxone

  • Prevents secondary cases by eradicating nasopharyngeal carriage

3. Safe Sexual Practices (Gonorrhea Prevention)

  • Consistent and correct condom use

  • Limiting number of sexual partners

  • Regular screening of high-risk individuals

  • Early diagnosis and complete treatment of patients and partners

4. Infection Control Measures

  • Early case detection and isolation

  • Prompt antibiotic treatment

  • Contact tracing

  • Reporting to public health authorities

5. Health Education and Awareness

  • Public education on:

    • Sexually transmitted infections

    • Symptoms and complications

    • Importance of early treatment

  • School and community-based programs

6. Surveillance and Public Health Programs

  • Monitoring antimicrobial resistance patterns

  • Outbreak investigation and control

  • Strengthening laboratory diagnostic capacity

 

MCQs

1. Neisseria are best described as:

A. Gram-positive cocci
B. Gram-negative bacilli
C. Gram-negative diplococci
D. Gram-positive diplococci
✅ Answer: C

2. Characteristic shape of Neisseria is:

A. Lanceolate
B. Kidney bean-shaped
C. Spherical clusters
D. Filamentous
✅ Answer: B

3. Family of Neisseria is:

A. Enterobacteriaceae
B. Micrococcaceae
C. Neisseriaceae
D. Streptococcaceae
✅ Answer: C

4. Which Neisseria species causes gonorrhoea?

A. N. lactamica
B. N. sicca
C. N. meningitidis
D. N. gonorrhoeae
✅ Answer: D

5. Which Neisseria species causes meningococcemia?

A. N. gonorrhoeae
B. N. meningitidis
C. N. flavescens
D. N. subflava
✅ Answer: B

6. Gram stain of Neisseria shows:

A. Gram-positive cocci in chains
B. Gram-negative bacilli
C. Gram-negative intracellular diplococci
D. Acid-fast bacilli
✅ Answer: C

7. Neisseria are:

A. Anaerobic
B. Facultative anaerobic
C. Strictly aerobic
D. Microaerophilic
✅ Answer: C

8. Optimal temperature for Neisseria growth is:

A. 25°C
B. 30°C
C. 35–37°C
D. 42°C
✅ Answer: C

9. Neisseria requires which atmosphere for optimal growth?

A. Anaerobic
B. High oxygen
C. 5–10% CO₂
D. Nitrogen-rich
✅ Answer: C

10. Selective medium for Neisseria is:

A. MacConkey agar
B. Blood agar
C. Thayer–Martin agar
D. Lowenstein–Jensen
✅ Answer: C

11. Chocolate agar supports growth of:

A. Only N. gonorrhoeae
B. Only N. meningitidis
C. All pathogenic Neisseria
D. Only commensal Neisseria
✅ Answer: C

12. Oxidase test in Neisseria is:

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

13. Catalase test in Neisseria is:

A. Negative
B. Positive
C. Variable
D. Not applicable
✅ Answer: B

14. N. gonorrhoeae ferments:

A. Glucose only
B. Maltose only
C. Glucose and maltose
D. No sugars
✅ Answer: A

15. N. meningitidis ferments:

A. Glucose only
B. Maltose only
C. Glucose and maltose
D. Lactose
✅ Answer: C

16. Capsule is present in:

A. N. gonorrhoeae
B. N. meningitidis
C. Both
D. Neither
✅ Answer: B

17. Major virulence factor of N. meningitidis is:

A. Pili
B. IgA protease
C. Capsule
D. LOS
✅ Answer: C

18. Endotoxin of Neisseria is:

A. Lipopolysaccharide
B. Lipoteichoic acid
C. Lipooligosaccharide
D. Exotoxin
✅ Answer: C

19. IgA protease helps Neisseria in:

A. Capsule formation
B. Immune evasion
C. Sporulation
D. Motility
✅ Answer: B

20. Gonorrhoea is transmitted mainly by:

A. Food
B. Water
C. Sexual contact
D. Insects
✅ Answer: C

21. Meningococcal infection spreads by:

A. Sexual contact
B. Respiratory droplets
C. Fecal–oral route
D. Blood transfusion
✅ Answer: B

22. Neonatal conjunctivitis is caused by:

A. N. meningitidis
B. N. gonorrhoeae
C. Chlamydia only
D. Streptococcus
✅ Answer: B

23. Waterhouse–Friderichsen syndrome is seen in:

A. Gonorrhoea
B. Typhoid
C. Meningococcemia
D. Tuberculosis
✅ Answer: C

24. Best specimen for diagnosing gonorrhoea in males:

A. Blood
B. CSF
C. Urethral swab
D. Stool
✅ Answer: C

25. Best specimen for meningitis diagnosis:

A. Urine
B. Blood
C. CSF
D. Sputum
✅ Answer: C

26. Gold standard test for gonorrhoea diagnosis is:

A. Gram stain
B. Culture
C. NAAT
D. Serology
✅ Answer: C

27. Latex agglutination test detects:

A. Antibodies
B. Capsular antigen
C. Toxins
D. DNA
✅ Answer: B

28. Which Neisseria shows maximum antibiotic resistance?

A. N. meningitidis
B. N. gonorrhoeae
C. N. lactamica
D. N. sicca
✅ Answer: B

29. Penicillin resistance in gonococci is due to:

A. Capsule
B. Efflux pumps
C. β-lactamase
D. Spore formation
✅ Answer: C

30. Current drug of choice for gonorrhoea is:

A. Penicillin
B. Ciprofloxacin
C. Ceftriaxone
D. Azithromycin
✅ Answer: C

31. Chemoprophylaxis for meningococcal contacts includes:

A. Ampicillin
B. Rifampicin
C. Penicillin V
D. Doxycycline
✅ Answer: B

32. Vaccine is available for:

A. N. gonorrhoeae
B. N. meningitidis
C. Both
D. Neither
✅ Answer: B

33. Serogroup B vaccine is:

A. Polysaccharide
B. Toxoid
C. Recombinant protein
D. Live vaccine
✅ Answer: C

34. Neisseria are non-motile because they lack:

A. Cilia
B. Flagella
C. Pili
D. Capsule
✅ Answer: B

35. Which test differentiates N. gonorrhoeae from N. meningitidis?

A. Oxidase test
B. Catalase test
C. Sugar fermentation
D. Gram stain
✅ Answer: C

36. Intracellular diplococci are commonly seen in:

A. Blood
B. CSF
C. Neutrophils
D. Epithelial cells
✅ Answer: C

37. LOS causes:

A. Immunity
B. Inflammation and shock
C. Capsule synthesis
D. Motility
✅ Answer: B

38. Complement deficiency predisposes to:

A. Gonorrhoea
B. Meningococcal infection
C. Syphilis
D. Tuberculosis
✅ Answer: B

39. Autolysis is commonly seen in:

A. N. meningitidis
B. N. gonorrhoeae
C. N. lactamica
D. N. flavescens
✅ Answer: B

40. Best prevention of gonorrhoea is:

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

41. Best prevention of meningococcal disease is:

A. Antibiotics
B. Vaccination
C. Isolation
D. Nutrition
✅ Answer: B

42. Which Neisseria is a commensal?

A. N. gonorrhoeae
B. N. meningitidis
C. N. lactamica
D. All
✅ Answer: C

43. Which is NOT a virulence factor?

A. Pili
B. Capsule
C. LOS
D. Spore
✅ Answer: D

44. Gonococci survive poorly outside host due to:

A. Capsule
B. Spore formation
C. Fragile nature
D. Motility
✅ Answer: C

45. Culture failure is common in:

A. Treated patients
B. Untreated patients
C. New infections
D. Neonates
✅ Answer: A

46. NAAT is preferred because it is:

A. Cheap
B. Rapid and sensitive
C. Culture-based
D. Manual
✅ Answer: B

47. Gonorrhoea in females is often:

A. Severe
B. Fatal
C. Asymptomatic
D. Self-limiting
✅ Answer: C

48. Thayer–Martin medium contains antibiotics to:

A. Enhance Neisseria growth
B. Kill Neisseria
C. Inhibit normal flora
D. Increase pigment
✅ Answer: C

49. Which antibiotic resistance is plasmid-mediated?

A. Cephalosporin
B. Penicillin
C. Rifampicin
D. Chloramphenicol
✅ Answer: B

50. Neisseria are exclusively:

A. Environmental organisms
B. Animal pathogens
C. Human pathogens
D. Plant pathogens
✅ Answer: C