Unit 4a – Almost done!

Chapter 15: Microbial Mechanisms of Pathogenicity How microbes cause disease (figure 15.9)

Remember? Pathogenicity: The ability to cause disease. Virulence: The extent of pathogenicity.

Most pathogens have a preferred portal of entry Salmonella typhi swallowed vs. rubbed Strep pneumonia inhaled vs. swallowed

Numbers of Invading Microbes _____: Infectious dose for 50% of a sample population. _____: Lethal dose (toxin) for 50% of a sample population. actual number depends on: virulence of pathogen strength of host defenses for same pathogen and same person, infective dosage varies from day to day with strength of body defenses ID50

Clickers… What is the LD50 for the bacterial toxin tested in the experiment below? Dilution # of animals # of animals mg/kg that died that survived 6 0 6 12.5 0 6 25 3 3 50 4 2 100 6 0

Adherence factors for attachment to host cells

attachment by capsule Remember Unit 1 discussion of Biofilms?

attachment by filaments

attachment by hook

attachment by viral spikes

Virulence factors: how pathogens cause disease Many pathogens have multiple virulence factors Virulence factors have 5 general effects adherence to host cells entering into host cells destruction of host cells avoiding phagocytosis evading immune responses Good Essay Question!

Some exoenzymes of virulence 1. collagenase: dissolves collagen (protein fibers in connective tissue); softens up a tissue so infection can spread Clostridium’s spread of gas gangrene 2. IgA proteases Destroy our IgA antibodies Gonorrhoea and meningococcal meningitis can do 3. hyaluronidase: dissolves hyaluronic acid (glue-like substance that holds cells together); helps infection to spread Streptococcus sp.

hyaluronidase dissolving hyaluronic acid

4. lecithinase: dissolves cell membranes; pathogen can digest cell contents

enzymes of virulence 5. coagulases: clot blood; fibrin fibers coat pathogen, prevent phagocytosis Staph (to wall off boils) 6. leukocidins: kill white blood cells Staph aureus 7. kinases: dissolve clots (e.g. streptokinase) 8. hemolysins: cause hemolysis (lysis of red blood cells) test for hemolysis on blood agar

alpha hemolysis: partial hemolysis, causes greenish zone around colony on blood agar

beta hemolysis: complete hemolysis, causes clear, colorless zone around colony

gamma hemolysis: NO hemolysis

Other virulence factors _________: prevents phagocytosis, helps pathogen attach to host cell

Toxins Toxin: Substances that contribute to pathogenicity. Toxigenicity: Ability to produce a toxin. Toxemia: Presence of toxin in the host's blood. Antitoxin: Antibodies our body produces against a specific toxin. Toxoid: Inactivated toxin used in a vaccine. When toxoids are injected as a vaccine, they stimulate antitoxin production so that immunity is produced Diphtheria and tetanus toxoid vaccination

Exotoxins Fig. 15.4

Endotoxins: Fig. 15.4

Endotoxins and the pyrogenic response figure 15.6

Sepsis and Septic Shock: pp. 639-641 (10th ed) Although blood is normally sterile, if the defenses of the cardiovascular and lymphatic systems fail, microbes could enter blood/lymph Septicemia: proliferation of pathogens in the blood Fever Sometimes causes organ damage Sepsis: systemic inflammatory response syndrome (SIRS) Mediators of inflammation into the blood stream rapid heart or respiratory rates High count of white blood cells Lymphangitis: inflamed lymph vessels

Fig. 23.2 Relationship between the cardiovascular and lymphatic systems

Sepsis and Septic Shock continued life-threatening systemic response to a bacterial infection First stage is sepsis Fever, chills and accelerated breathing & heart rate Overwhelming infection leads to low blood pressure and low blood flow. Shock Vital organs, such as the brain, heart, kidneys, and liver may not function properly or may fail. Decreased urine output from kidney failure may be one symptom. Severe sepsis to septic shock

Types Gram-Negative Sepsis Endotoxic shock 750,000 cases/ yr in US; at least 225,000 are fatal (textbook pg. 640) Gram-Positive Sepsis Staph, Strep & Enterococcus Puerperal Sepsis Childbirth fever Nosocomial infection Strep. pyogenes most frequent cause

high risk patients: Burns Age >60 or the very young post-surgery (especially intestinal) abdominal trauma advanced cancer diabetes

septic shock mechanism: pathogens release endotoxins, exotoxins: these products stimulate release of chemicals from various host cells that produce the symptoms: low blood pressure, especially when standing rapid, weak pulse fever (hypothermia in burn patients) Low urine output Agitation, confusion

septic shock symptoms: sudden high fever disorientation, confusion, irritability, somnolence edema (swelling): face, hands, feet dyspnea edema may constrict pharynx bronchioles contract death by asphyxiation may result circulatory stagnation inadequate blood volume causes low blood pressure, rapid weak pulse, possible total stagnation of bloodflow

septic shock treatment (not necessarily in this order) inject epinephrine open airway (intubation or tracheostomy) oxygen if needed restore blood volume: rapid IV draw blood for blood gases and to culture pathogen broad spectrum drug (until pathogen is known) monoclonal antibodies against endotoxin

Back to figure 15.9

In summary: Damage to host cells 1. By using the host’s nutrients Siderophores: proteins pathogens produce to get the iron they need from the host 2. By causing direct damage in the immediate vicinity of the invasion 3. By producing toxins

Portals of Exit Respiratory tract Coughing and sneezing Gastrointestinal tract Feces and saliva Genitourinary tract Urine and vaginal secretions Skin Blood Biting arthropods and needles or syringes