BSCI 424 — PATHOGENIC MICROBIOLOGY — Fall 2000


Streptococcus pneumoniae Summary



MORPHOLOGY AND PHYSIOLOGY:

  Encapsulated Gram-positive diplococci or short chains; Oval or lancet-shaped cells (0.5-1.2um) (see WebLinked image; see WebLinked image; see WebLinked image)
  Capsular antigen in virulent strains: Complex polysaccharide; Cross reactive
  Gram positive but stain poorly and may appear gram negative

  No Lancefield group-specific antigens


  Alpha hemolysis (aerobically); beta hemolysis (possible anaerobically)
  Growth on surface of blood agar is alpha-hemolytic when incubated aerobically
  Subsurface or anaerobic growth may show beta-hemolysis due to production of pneumolysin which is oxygen labile

  Autolysis of colonies with aging


  Fastidious Growth Requirements
  Enriched media with 5% defibrinated blood (provides catalase)
  Increased carbon dioxide for 5-10% of strains (capnophilic)
  Ferment carbohydrates; Major endproduct is lactic acid; High concentrations of glucose in medium is inhibitory as lactic acid levels become toxic (like Grp A streptococci)
  Choline requirement (phosphocholine in cell wall is unique to S. pneumoniae) for cell wall hydrolysis; Amidase (autolytic enzyme) inactive without choline and cell division stops
  Catalase negative (unlike staphylococci); Accumulation of hydrogen peroxide inhibits growth; Exogenous source of catalase needed for growth (e.g., blood)

  Two forms of teichoic acid polymer (galactosamine and phosphocholine) in cell wall


  Cell surface exposed (C-substance): Precipitates a serum globulin fraction known as C-reactive protein (CRP) in the presence of calcium


CLINICAL SYNDROMES:

  Remains a leading cause of morbidity and mortality


  Pneumonia (Pneumococcal Pneumonia; Lobar Pneumonia)
  Aspiration (inhalation) of endogenous oral pneumococci into lung alveoli
  Bacteria multiply rapidly in nutrient-rich edema
  Sudden onset with shaking chills and sustained fever
  Erythrocytes leak from capillaries
  Phagocytic cells (neutrophils, followed by alveolar macrophages) migrate and phagocytose and destroy pneumococci
  Productive cough with blood in sputum
  Pleurisy common
  Generally localized in lower lobes
  Children and elderly may have diffuse bronchopneumonia
  Pneumococcal lesion can be observed by X-ray
  Radiological resolution (clean chest X-ray) within 2-3 weeks with antimicrobial therapy

  Bacterial Sinusitis (paranasal sinuses)
  Often antecedent upper respiratory tract viral infection with PMN obstruction of sinuses and ear canal
  All age groups

  Otitis Media (middle ear inflammation):
  Often antecedent upper respiratory tract viral infection with PMN obstruction of sinuses and ear canal
  Primarily in young children

  Meningitis: CNS (central nervous system) involvement after bacteremia, sinusitis or otitis media, head trauma
  Primarily in pediatric population
  Mortality and severe neurological complications are 4-20 times more likely than with meningitis caused by other organisms

  Bacteremia:
  25-30% with pneumonia
  80% with meningitis
  Endocarditis possible

EPIDEMIOLOGY:

  Colonizes oropharynx and/or nasopharynx; Spreads to normally sterile site


  Stimulates local inflammatory response, but evades phagocytic killing


  Carriers (5-75% Incidence): Transient colonization of throat and nasopharynx by a succession of different serotypes; Duration decreases with each successive serotype (serotype-specific immunity); Disease generally from newly acquired strain


  Serious disease most commonly in young children or elderly adults


  Often preceded by (antecedent) respiratory viral infection (e.g., influenza, measles)


  Conditions interfering with normal clearance of bacteria predisposes host to pneumococcal infections
  Chronic pulmonary disease
  Alcoholism
  Congestive heart failure
  Diabetes mellitus
  Chronic kidney disease
  Splenic dysfunction or splenectomy: Decrease in clearance from blood and defective early antibody production

PATHOGENESIS AND IMMUNITY:

  Pathogenesis primarily due to host response to infection


  Three Classes of Virulence Factors:
  1. Colonization and migration (spreading)
  2. Tissue destruction
  3. Phagocytic survival

  Cellular components:
  Complex polysaccharide capsule: Antiphagocytic
  Encapsulated (smooth) strains are virulent
  Nonencapsulated (rough) strains are avirulent
  Type-specific anticapsular antibodies are protective
  Capsular polysaccharides are soluble (a.k.a., specific soluble substances) and free polysaccharides can bind opsonins and further inhibit phagocytosis
  Protein adhesin: Binds to oropharyngeal epithelium enabling initial colonization
  Teichoic acid: Activate alternative complement pathway; C5a production mediates inflammation
  Peptidoglycan fragments: Activate alternative complement pathway; C5a production mediates inflammation
  Phosphorylcholine: Mediates tissue destruction, spreading, and protection from opsonization and phagocytosis; Binds to host cell receptors for platelet-activating factor allowing entrance into cells

  Extracellular components:
  Pneumolysin (pneumolysin O): Multifactorial cytotoxin
  Biochemically similar to Streptolysin O (O2 labile)
  Assists spreading by destroying ciliated epithelial cells by binding cholesterol in host cell membranes and causing pore formation
  Tissue destruction mediated by activation of classic complement pathway; C3a and C5a production with activated leukocytes producing cytokines (e.g., IL-1, TNF-alpha) which result in enhanced inflammatory cell response, fever, tissue damage, etc.
  Inhibits phagocytic killing by suppressing oxidative burst
  Secretory IgA protease: Assists spreading by enzymatically disrupting secretory IgA (sIgA) clearance of bacteria

  Immune Response:
  Naturally acquired immunity: Type-specific anticapsular immunity
  Artificially acquired immunity: Immunization via polyvalent vaccine prophylaxis
  Purified capsular material from most common serotypes (23 different polysaccharides covering 94% of clinically relevant serotypes); Until recently this formulation was not effective in young children or elderly adults or in other high risk groups
  In 1999, a vaccine formulation was shown to be effective and has been approved by the FDA for use against otitis media in young children

LABORATORY IDENTIFICATION:

  Quellung (capsular precipitation; swelling) reaction: Anticapsular antibodies cause an increase in refractivity of the capsule making it readily apparent by microscopy


  Susceptibility to optochin (ethylhydrocupriene dihydrochloride)


  Soluble in bile: Colonies dissolve when exposed to drop of bile (differentiates from alpha-hemolytic streptococci and Enterococcus); Autolysis after bile activation of autolysins; Also performed in broth culture with clearing


TREATMENT:

  Drug of Choice: Penicillin; Alternates: Cephalosporins, erythromycin, chloramphenicol (meningitis); Resistant to tetracycline


  Multiple Antibiotic Resistance (Multidrug Resistance): Recognized in 1977; Including low level resistance to penicillin


  Dramatic increase in frequency of moderate resistance and in the emergence of high levels of resistance (High level resistance: MIC > 2.0 ug/ml)
 

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Copyright © 2000, D.M. Rollins and S.W. Joseph
Revised: August 2000
URL: http://life.umd.edu/classroom/bsci424