Neisseria, Haemophilus and Bordetella Flashcards
What Gram are Neisseria?
Gram Negative
What part of N. meningitidis results in septic shock?
The lipopolysaccharide (endotoxin) of Neisseria meningitidis is a potent stimulator of inflammation resulting in the septic shock syndrome.
What are the 4 general characteristics of Neisseria?
- Gram-negative “kidney bean” diplococci
- Endotoxic lipopolysaccharide complexed with protein in outer membrane
- Growth enhanced in CO2
- Fastidious species require enriched media (chocolate agar)
Are Neisseria oxidase positive or negative?
OXIDASE POSITIVE
What is the only sugar N. gonorrhea oxidizes?
Glucose
What sugars does N. meningitidis oxidize?
Glucose and Maltose
What immune component is required to fight Neisseria?
Complement
What 2 structures confer virulence to Neisseria menigitidis?
Pili - attachment
Capsule - bloodstream invasion and survival and possibly CNS penetration
What is the pathogenesis of Neisseria meningitidis?
- Attachment - microvilli of nonciliated nasopharyngeal cells via pili
- Traverse cell in vesicle to submucosa
- Damage ciliated cells
- Bloodstream survival enhanced by antiphagocytic
polysaccharide capsule - Endotoxin mediated activation of complement leading to shock and hemorrhage
- CNS inflammation generated by cell wall peptidoglycan, LPS, other bacterial products and is mediated by IL-1 and TNF
What are the clinical manifestations of N. meningitidis infection?
- Respiratory colonization followed by overt disease or transient carrier state
- Meningitis
- Skin: petechiae → purpura
- Meningococcemia: shock, hemorrhage and purpura,
destruction of adrenals
What are the identifying features of N. meningitidis in the lab?
- Gram smear- Cerebrospinal fluid (CSF)
- Cultures- CSF, blood, skin
- Cultures – Oxidase positive, oxidize glucose and maltose
- Nonselective media (blood or chocolate agar)
What is the main treatment for N meningitides?
Penicillin - resistance uncommon
What serotype is not used in N. meningitides vaccines?
Serogroup B cannot be used in the vaccine as it is non-immunogenic
What is PorB of N. gonorrhea?
PorB - Outer membrane protein I (Por proteins) – Porin
a. Pores (channels) in organism
b. Facilitates epithelial cell invasion
What is Opa of N. gonorrhea?
Opa - adherence proteins confer opaque appearance to colony which results from Opa-mediated adherence between cells
Opaque associated with localized
Transparent disseminated
What 2 things contribute to the antigenic diversity of N. gonorrhea?
Pili - Antigenic variation
Opa – Phase variation
How does pili antigen variation occur in N. gonorrhea?
Genetic recombination by transfer of variable sequences form unexpressed (silent) loci, pilS to expression locus, pilE
How does Opa phase variation occur in N gonorrhea?
Can switch on and off as many as 11 different Opa
genes throughout the genome creating variation
What is the transmission of N. gonorrhea?
Mucosal transmission (genital, mouth, anus, eye) by direct contact
What is the pathogenesis of N. gonorrhea?
- Attachment via pili and Opa
Genetic variation of ligands evades immune responses - Invasion and damage
a. Epithelial cell invasion involves PorB and other outer membrane proteins
b. Epithelial cell invasion has been demonstrated in salpingitis, but role in uncomplicated mucosal infection not demonstrated
c. Lipopolysaccharide and peptidoglycan fragments incite inflammatory response - Spread
a. Prostate, epididymis and paracervical glands by direct
extension
b. Possibly carried by sperm to fallopian tubes
c. Serum resistant strains invade the bloodstream and
disseminate to skin, joints
What are the clinical manifestations of N. gonorrhea?
Urethritis
Cervicitis
Prostatitis and pharyngitis - often asymptomatic
Conjunctivitis
How does N. gonorrhea evade the immune system?
a. Antigenic and phase variation evade immune response
b. Resist phagocytosis (Opa and pili)
c. IgA 1 protease
d. Evade serum antibody and complement mediated killing
e. Bind “blocking antibodies” to Rmp – Reduction Modifiable Protein
What are the methods for the identification of N. gonorrhea?
Gram Stain (95% sensitive in men; less in women)
Culture
Gene Amplification
What is the treatment for N. gonorrhea?
Ceftriaxone PLUS azithromycin
Antibiotic resistance is a BIG problem with N. gonorrhea
What are the characteristics of Haemophilus influenzae?
It is a small Gram-negative coccobacilli
Grows on chocolate agar (lysed blood)
What factors does H. influenzae require to grow?
X factor (hematin) Y factor (NAD)
What is the main virulence factor of H. influenzae?
Type B capsule - polyribitol phosphate (PRP)
What led to the drastic decrease in the rate of H. influenzae infection?
Type B decreased the rate of it by 94%
What is the transmission of H. influenzae?
Respiratory droplets
What is the transmission of N. meningtidis?
Respiratory droplets
What is the pathogenesis of H. influenzae?
- Adhere - Pili, OMPs
- Transcytose like Neisseria
- Encapsulated strains invade bloodstream
- Endotoxin - local and systemic inflammation
What are the clinical manifestations of Type B H. influenzae?
a) Meningitis - children
What are the manifestations of unencapsulated H. influenzae?
a) Otitis media
b) Acute and chronic sinusitis
c) Bronchitis
What is the treatment for H. influenzae?
Ampicillin
Cephalosporins
Vaccine as preventative measure
H. parainfluenzae Disease
Respiratory
H. aegyptius Disease
Conjunctivitis
H. (Aggregatibacter) aphrophilus Disease
Endocarditis
H. ducreyi Disease
Chancroid (STD)
What are the characteristics of Bordella pertussis?
Aerobic
Gram-negative coccobacilli
What are the main virulence factors of B. pertussis?
- Adhesins
- Pertussis Toxin
- Tracheal cytotoxin - peptidoglycan fragment
What is the function of Pertussis Toxin?
AB subunit - A - S1 enzymatic, B – S2-S5 binding Subunits
A catalyzes ADP (from NADP) ribosylation of a
cellular regulatory protein (G- protein) which prevents inactivation of activated adenylate cyclase
B subunits bind to receptors on ciliated respiratory cells and phagocytic cells
Biologic effects of PT include: Increased respiratory secretions, mucus production and lymphocytosis
What is the function of Tracheal cytotoxin?
Tracheal cytotoxin – fragment of peptidoglycan that binds to and causes extrusion of ciliated respiratory epithelial cells. The toxin also stimulates IL-1 release (fever)
What is the function of Dermonecrotic toxin?
Dermonecrotic toxin – causes ischemic necrosis
What is B. pertussis transmitted by?
Spread by airborne droplets, highly infectious
What is the reservoir of B. pertussis?
Sub-clinical adults
What is the pathogenesis of B. pertussis?
- B. pertussis attaches to ciliated epithelial cells by adhesins
- Tracheal cytotoxin and possibly other toxins destroy ciliated
cells, extrude them from border - Adenylate cyclase exerts inhibitory effects on phagocytic cells
- Pertussis toxin produces systemic manifestations including enhanced respiratory secretions and mucus production
contributing to cough as well as lymphocytosis - Lipopolysaccharide – stimulates cytokine release
What are the clinical manifestations of B. pertussis?
Catarrhal stage - rhinorrhea, fever, sneezing, anorexia
Paroxysmal cough - up to 50 times a day for 2-4 weeks.
Inspiratory whoop, vomiting, mucoid secretions, marked
lymphocytosis
Convalescent stage - cough gradually fades
What is required for B. pertussis culture?
Specialized media – Regan-Lowe charcoal medium
What is the treatment for B. pertussis?
Azithromycin, clarithromycin, erythromycin
What are the vaccines available for B. pertussis?
DTaP, which contains one of the acellular pertussis vaccines, made from purified, detoxified pertussis toxin (PT), filamentous hemagglutinin (Fha), and Pertactin (Pn).
A dose of vaccine containing a reduced amount of pertussis antigens, Tdap, is recommended for all adults in place of a routine.
