Download Micro Chapter 13 [4-20

Micro Chapter 13: Pneumococcus and Bacterial Pneumonia
Streptococcus pneumonia (aka pneumococcus) is a leading cause of serious infection, especially
bacterial pneumonia
Strep pneumonia commonly colonizes the mucosal surface of the nasopharynx without causing disease,
unless host factors allow it to access normally sterile sties, like the lung, where it can trigger an acute
inflammatory response
Strep pneumonia has a thick layer of polysaccharide on its surface, which inhibits host clearance by
complement and phagocytosis
Strep pneumonia is α-hemolytic, and ferments, but can tolerate oxygen, which lets it survive in the
airway
Strep pneumonia, like other strep, lacks catalase, so its metabolism makes lots of hydrogen peroxide
Strep pneumonia inhibit growth of competitive members of the microflora, which together with
released pneumolysin, causes most the damage to tissue and inhibition of host defense
Like other gram-positives, strep pneumonia are surrounded by a thick cell wall, which has parts that are
recognized by innate immunity and responsible for stimulating inflammation
In the stationary phase of growth, strep pneumonia express autolysin, which degrades its own cell wall,
which allows release of its inflammatory mediators
Outside the cell wall is a capsule that gives the strep pneumonia a mucoid or “smooth” look to the
colonies on agar
-
-
Capsules are made of polysaccharide that completely envelop the cell, which hides the stuff
inside it from the immune system
The capsule prevents phagocytosis and complement
o Normally, complement is a great defense that activates a membrane attack complex to
lyse the bacteria
o Other things can’t be killed by complement alone, so complement opsonizes to recruit
phagocytes and neutrophils
o Strep pneumonia gets around this by surrounding itself in its capsule, which has
polysaccharides that don’t allow opsonization well, unless there’s previously made
antibodies to its capsule
o The capsule itself can be antigenic though, so antibodies are eventually made against
the capsule to allow opsonization and phagocytosis
Capsules are important for an organism to live in the blood, where complement is strongest
So the capsule lets strep pneumonia spread from its original site of infection at the respiratory
tract
Meningitis – inflammation of the meninges
o
-
-
Usually needs continuous increased amounts of bacteria in the blood to overcome the
blood-brain barrier
o Strep pneumonia is a common cause of meningitis, due to its capsule
Nonencapsulated strep pneumonia rarely cause disease, since they’re easily opsonized and
phagocytosed
Capsule polysaccharides are very immunogenic and often the main antigen on the organism
o Since the capsule polysaccharides are the target of selective pressures from immune
response, there is a lot of variation in these polysaccharides in strep pneumonia, and
the antigenic differences in strains comes from differences in the polysaccharides
In a quelling rxn, you add an antibody to look for and bind the capsule
Antibodies to capsules prevent future infection by the pathogen
Encounter with strep pneumonia (pneumococcus):
-
-
Strep pneumonia is the most common form of bacterial pneumonia acquired in the
community
Strep pneumonia is one of the leading infectious causes of mortality
o Incidence is highest in children and in people over 40
Anemia, alcoholism, HIV, absent spleen, and other things that lower the immune system will all
predispose to an strep pneumonia infection
Strep pneumonia infections are also seasonal, with the most amount of infections happening in
the winter and early spring, often after a recent upper respiratory viral infection
Strep pneumonia is also one of the leading causes of acute otitis media, acute sinusitis, and
chronic bronchitis
o Otitis media is the most common reason for a kid to come to the doctors
Strep pneumonia can also get to sterile places it shouldn’t be, like the peritoneal cavity
(peritonitis), joints (septic arthritis), or heart valves (endocarditis)
The environmental reservoir of strep pneumonia is humans, but most people harboring it don’t
have symptoms because strep pneumonia is usually a nonharmful commensal microbiota
Strep pneumonia love the respiratory tract
When a host first meets strep pneumonia, the organism colonizes onto the nasopharynx
Colonization then either results in clearance of the organism, asymptomatic persistence (called
carrier state), or progression to disease
Some serotypes of strep pneumonia are more virulent than others
Strep pneumonia are carried by up to 2/3 of preschool kids
The older you get, the less likely you’re colonized, with only 10% of adults colonized
Transmission from person-to-person happens through droplets of respiratory secretions that
remain airborne over distances of a few feet
o Transmission of strep pneumonia is highly efficient
Entry of strep pneumonia (pneumococcus):
-
Disease happens when strep pneumonia spreads from the nasopharynx to sterile parts of the
airway
Normally, the lungs are protected by the pathway air has to travel to get there, the epiglottis
that prevent aspiration, the cough reflex, the mucus that is always swept up by cilia, and
alveolar macrophage
o These are great at preventing spread of infection from upper respiratory tract to lower
respiratory tract
o Things like smoking and viral infection can weaken these defenses
Spread, multiplication, and damage by strep pneumonia (pneumococcus):
-
Four stages to the inflammatory process of strep pneumonia:
o In the first stage – the alveoli fill with serous fluid that has many organisms, but few
inflammatory cells
 The pneumococcal cell wall stimulates this outpouring of fluid, and then the
inflammatory response
 The fluid that fills the alveoli serves as a means for bacteria multiplication and
spread
 This outpouring of fluid messes with gas exchange in the lungs
o The second stage is called early consolidation – alveoli are infiltrated by neutrophils and
RBCs
 They’re recruited by chemokines from the strep pneumonia and alternative
pathway of complement
 This leads to typical inflammation
 You now fight the infection, as the strep pneumonia has a capsule to resist
phagocytosis, but if the strep does get ingested by phagocytes, it’s killed
 To help make the strep pneumonia more ingestible:
 If you’ve had contact with the strep pneumonia before, you’ll have
predeveloped antibodies to that capsule to opsonize & facilitate uptake
 If not, innate immunity still can opsonize it, especially by complement
that bind to the bacteria when there’s no antibodies, to opsonize
o Complement binding is more efficient against some strains than
others, make some more or less virulent
 Also, C reactive protein (CRP) reacts with phosphorylcholine on
pneumococcal teichoic acid
o Binding of C reactive protein to the bacteria surface activates
complement through the classical pathway
o CRP levels rise quickly in inflammation, so it is called an acute
phase reactant
o The third stage of strep pneumonia is called late consolidation – alveoli are packed with
victorious neutrophils, and few remaining pneumococci

-
-
These areas of the lungs are heavy and resemble the liver in appearance, so
this state is called hepatization
o In the final stage, called resolution – neutrophils are replaced by macrophage, which
clear the debris
 Most of the time, the lung is restored completely back to normal
 There was no necrosis, unlike other forms of pneumonia, so no fibrous scars
are needed
Pneumococcal pneumonia can cause both local and distal problems
o The most common local problem is pleural effusion – outpouring of fluid into the pleural
space
 Usually the effusion exudate is sterile, but rarely it can have bacteria, and infect
the pleural space, called empyema
o Distal problems happen when strep pneumonia get into the blood
 In early pneumonia, the strep may get into the lymph to enter blood
 ¼ of all pneumonias will show organisms on blood culture
 Spleen helps clear blood organisms
So strep pneumonia infection is characterized by an acute inflammatory response, resulting in
respiratory tract infections, including otitis media, sinusitis, chronic bronchitis, and
pneumonia, and invasive things like meningitis and bacteremia
Diagnosis of strep pneumonia (pneumococcus):
-
-
Strep pneumonia is the leading cause of lobar pneumonia, acute otitis media, chronic
bronchitis, and acute sinusitis
You want to look at the sputum with a gram stain
o Suggests strep pneumonia when the gram stain has neutrophils and lots of lancetshaped gram-positive diplococci
You can then culture the sputum to be sure
o Pnemococcal colonies show α-hemolysis, which looks green/brown from hydrogen
peroxide making, that isn’t cleared
o But most other strep normally found in the heavily colonized upper respiratory tract are
also α-hemolytic, you need to differentiate by checking sensitivity to optochin, as well as
solubility in bile salts
Treating and preventing strep pneumonia:
-
Penicillin works great against strep pneumonia, and for people allergic you can use macrolides
(50S) or some fluoroquinolones (DNA replication)
Resistance is growing to penicillin, but ¾ of strains of strep pneumonia can still be treated with it
Resistance in the other ¼ is from mutations in enzymes that cross-link the cell wall, and are
normally bound and inactivated by penicillin, called pencillin-binding proteins
o So they no longer bind penicillin, so there’s no problem in cell wall making
Strep pneumonia infections can show a breathing pattern called splinting, where they don’t want to
move a side of the chest because it hurts on inspiration
-
Splinting indicates inflammation of the pleura
Classic features of strep pneumonia are abrupt onset of severe symptoms, rust colored sputum, the
whole lobe of the lung is involved (lobar consolidation), leukocytosis