Bacteria Chapter 12: Capsule as Virulence Factor Flashcards
What do polysaccharide capsules do?
- prevents phagocytosis — attachment and engulfment by neutrophils or macrophages
- prevent other host cellular immune responses
- prevent deposition of antibodies and complements on bacterial surface — avoids complement-mediated killing
What bacteria uses capsule to avoid phagocytosis by host macrophages?
Streptococcus pneumoniae
What are S. pneumoniae characteristics?
- non-motile
- non-sporulating
- Gram-positive
What is S. pneumoniae sensitive to?
- heat
- cold
- drying
How is S. pneumoniae transmitted?
close person-to-person contact with respiratory droplets
What are the major virulence factors of S. pneumoniae?
- polysaccharide capsule
- adhesins
- pneumolysin
What is pneumolysin?
toxin that binds to cholesterol in host cell membrane and disrupts them by forming pores
What are some diseases caused by S. pneumoniae?
- otitis media (ear infection)
- pneumonia (inflammation of lungs)
- bacteremia (bacteria in blood)
- meningitis (inflammation of membrane surrounding brain and spinal column)
S. pneumoniae causes more deaths than any other vaccine-preventable disease
-
What does S. pneumoniae do as a transient member of microbiota?
colonizes nasopharynx of 40% of healthy adults and children with no adverse effects
What does S. pneumoniae do as an opportunistic pathogen?
common bacterial complication of influenza and measles infections
Why are smokers more at risk of S. pneumoniae infection?
cigarette smoke can injure airways and damage cilia
Why are alcoholics at increased risk of S. pneumoniae infection?
alcohol acts as sedative and can diminish reflexes that trigger coughing and sneezing
What are the minimum criteria for identification of S. pneumoniae?
(observe sputum, blood, or CSF)
- Gram-positive staining
- hemolytic activity
- bile sensitivity
What are the different types of hemolysis that S. pneumoniae may cause?
- alpha hemolysis
- beta hemolysis
- gamma hemolysis
What is alpha hemolysis?
in aerobic conditions:
partial or greening hemolysis from reduction in RBC hemoglobin
What is beta hemolysis?
in anaerobic conditions:
complete lysis of RBCs surrounding colony
What is gamma hemolysis?
lack of hemolysis of RBCs around the colony
What problems may arise when diagnosing S. pneumoniae?
- bacteria can be difficult to grow, therefore a negative result does not necessarily rule out pneumonococcal pneumonia
- positive culture from sputum sample may be the result of contamination from bacteria in the mouth of a colonized patient
What is used for treatment of S. pneumoniae?
- penicillin & penicillin-derivatives used to work well, but penicillin-resistant strains are becoming more common
- erythromycin or tetracycline are alternative treatments, but there’s also resistance to these
What does the current vaccine for S. pneumoniae contain?
purified, capsular polysaccharide antigens of 23 types of S. pneumoniae
- cross-reactivity occurs for several of the capsular types
What is cross-reactivity?
antibody against one serotype will bind to another serotype because of a shared epitope
Is the current S. pneumoniae vaccine given to everyone?
no — only high-risk individuals
Does the current vaccine elicit a strong immune response? Why?
no — polysaccharides are less immunogenicity than proteins
especially true in high-risk groups
What does the conjugate vaccine for S. pneumoniae consist of?
polysaccharide antigens covalently bonded to proteins (to make the vaccine more immunogenic)
covers only 7 capsular types
Compare the mechanism of immunogenecity of polysaccharide vaccines (PPV) and polysaccharide-protein conjugate vaccines (PCV).
PPV: T cell independent B cell activation
- B cell → plasma cell →IgM
- not effective in children < 2 years old
- no memory effect
PCV: T cell dependent B cell activation
- APC + T cell interaction + B cell interaction → plasma cell → IgG
- B cells also become memory B cells
- effective in children < 2 years old
- has memory effect
Is the capsule of S. pneumoniae toxic?
non-toxic and does not induce inflammatory response
How can different capsular types be identified?
serological testing
- sample of bacterial colony is mixed with a specific monoclonal antibody
- positive test is indicated by capsule swelling, which can be viewed under a phase-contrast microscope
What is the essential determinant of the virulence of S. pneumoniae? Why?
capsule
- encapsulated = pathogenic
- mutant without capsule = non-pathogenic
What is the primary reason S. pneumoniae can invade and grow?
their resistance to host phagocytic responses
- antibodies and/or complement cannot bind to bacterial cell surface
- capsule interferes with phagocytosis by preventing C3b opsonization of bacteria and formation of C3 convertase that would normally result in MAC
Can S. pneumoniae be part of the microbiota of healthy people?
yes
The vaccine against S. pneumoniae consists of only 23 of the 90 possible capsule types, yet it induces humoral immunity to more than the 23 capsules types present in the vaccine. How would you explain this observation?
- many of the polysaccharides may share a common structure
- antibody produced to one specific polysaccharide may cross-react with other polysaccharides that have similar molecular structure
- binding of these cross-reacting antibodies to bacteria with capsule types not present in the vaccine may not be precise, but is adequate to opsonize bacteria so that phagocytic cells can engulf it
