NEISSERIA

J621/LIFS 675
Medical Microbiology

NEISSERIA

A. INTRODUCTION

The family includes several genera (Neisseria, Branhamella, Moraxella).
Small Gram negative, non-motile diplococci. Kidney bean shaped; N. gonorrhoeae (gonococci) and N. meningitidis (meningococci) are pathogenic for humans.
Pathogenic Neisseria are typically found intracellularly within polymorphonuclear leukocytes.
Gonococci and meningococci are related closely, with 70% DNA homology. However, there are some distinguishing characteristics.

**Comparison of Gonococcal and Meningococcal Characteristics**
Gonococci	Meningococci
No polysaccharide capsule	Polysaccharide capsule present
Usually contain plasmids	Usually do NOT contain plasmids
Genital infection etiology	URI and meningitis etiology

B. PHYSIOLOGY

FASTIDIOUS. Growth within 48 h on enriched media (Mueller-Hinton or Thayer-Martin agar). The Neisseria must be incubated in an atmosphere containing 5% CO2 (candle jar).
Colony morphology: Nonpigmented convex, mucoid colonies are non-hemolytic (pathogenic organisms only). Mucoid appearance indicates the presence of a capsule. N. lactamica, N. subflava, N. falavescens produce yellow colonies. N. sicca colonies are opaque, brittle and wrinkled. M. catarrhalis colonies are nonpigmented or pinkish gray.
Energy is obtained by FERMENTATION with various sugars. Both N. meningitidis and N. gonorrghoeae ferment glucose. N. meningitidis ferments maltose.
Other characteristic fermentation patterns distinguish the distinct species. No gas is produced.
OXIDASE POSITIVE: this is the key test for identification of Neisseria.

C. VIRULENCE FACTORS AND ANTIGENIC STRUCTURE

Antiphagocytic CAPSULE composed of complex carbohydrates (N. meningitidis). There are thirteen serogroups, divided according to capsular polysaccharide composition. Types A,B,C, and Y are most commonly associated with disease.
There are also 5 classes of outer membrane proteins and 13 serotypes. Type 2 and 15 are associated with epidemic disease.
PILI allow the attachment of the organism to the nonciliated mucosal epithelium, allowing the establishment of a relationship with the host. Pili are composed of stacked PILIN protein, and antigenically different for various strains. Bacterial adherence is considered to be the most important virulence factor in the Neisseria.
Lipopolysaccharide (LPS)-a cell wall component, this endotoxin is important in disseminated gonorrhea infection. More than one antigenic type can be expressed simultaneously. Important in pathogenicity.
IgA1 protease-IgA1 makes up the greater percentage of the IgA in human secretions, and it is susceptible to degradation by the Neisseria protease. The host produces IgA1 and IgA2 as the major nonspecific defense mechanism to prevent bacterial adherence to the respiratory tract mucosa.
Maintenance within PMNs-The organisms are endocytosed after attaching to the surface of an epithelial cell. The gonococcus produces a substance that prevents fusion of the phagosome with a lysozome.
Protein Antigens

Protein I--18 serotypes identified by differences in the 34-37 kDa transmembrane protein used to form pores for nutrient transfer (porin).
Protein II--0 to 3 of the 10 genes encoding this protein may be expressed. 24-32 kDa protein involved in bacteria-to-cell contact.
Protein III-conserved 33 kDa protein interacts with Protein I to form pores.

D. CLINICAL DISEASE

Moraxella catarrhalis (formerly Branhamella catarrhalis)-previously only considered to be normal flora, now is known to cause pneumonia, suppurative sinusitis and otitis media infrequently.
Neisseria meningitidis (meningococcal infection)

Neisseria meningitidis is the etiologic agent for bacterial meningitis.
Arthritis is frequently a secondary disease with the presence of Neisseria meningitidis infection.
Fluorescent Antibody Test: Can be used to diagnose gonococcal infection, especially with spinal and joint fluid specimens. Both of these should be sterile under normal conditions.
Meningococcemia: a septicemia due to infection with Neisseria meningitidis which is a life-threatening illness.
Waterhouse-Friderichsen syndrome is associated with meningococcemia; it is commonly diagnosed at autopsy and is characterized by bilateral cortical necrosis of the adrenal glands.

Neisseria gonorrhoeae (gonnococcal infection)

Gonorrhea is highly transmissable due to the short incubation period for Neisseria gonorrhoeae, the high rate of asymptomatic carriers (usually female), and the increasing antibiotic resistances for the genus as a whole.
Increased antibiotic resistance, probably due to penicillinase plasmid transfer from Haemophilus. Gonnococci that obtain the plasmid become penicillinase producing Neisseria gonorrhoeae (PPNG). Tetracycline resistance in some isolates appears to have been transferred from Streptococcus.
Changing sexual patterns have altered the picture of sexually transmitted disease forever, increasing the incidence of gonorrhea.
Urethritis/Cervicitis/Vaginitis: Inflammation and infection begin in the cervix or urethra and travel upward to the oviducts or epididymis.
Salpingitis: Infection of the Fallopian tubes.
Pelvic Inflammatory Disease: Occurs when the infection reaches the peritoneal cavity.
Bacteremia/Disseminated Gonococcal Infection: This can result from PID. There is a risk of developing disseminated intravascular coagulation due to the Neisseria endotoxin.
Opthalmia Neonatorium: Gonococcal infection of the eyes in the newborn.
Bartholin's Gland Abcess: Occurs in females only.
Opthamitis: Occurs in adults where the gonococci have been rubbed in the eye.
Arthritis: Due to immune complex formation and deposition in the joints.

E. DIAGNOSIS

Urethritis: Sample of urethral exudate can be taken from a male patient and a Gram stain performed. Gram negative gonnococci found within polymorphonuclear leukocytes is presumptive evidence for gonorrhea.
In the female the diagnosis is not as simple because because a cervical exudate will contain Neisseria sp. that are normal vaginal flora. The cervical exudate sample must be cultured on Thayer-Martin agar and also on nutrient agar.
Cultures must be tested for oxidase positive colonies and positive glucose fermentation (differential fermentation).
Diagnostic kits such as GonnoCheck II are also available.

F. TREATMENT
Penicillin is the DOC. The addition of probenecid prolongs the peak levels of penicillin in the blood. Tetracycline is the secondary DOC. It is used in the case of penicillin allergy or PPNG. Tetracycline will also be effective if other STDs are present.