Chapter 15: Microbial Mechanisms of Pathogenicity

1. Chapter 15:Microbial Mechanisms of Pathogenicity

2. Microbial Mechanisms of Pathogenicity • Pathogenicity: The ability to cause disease

3. Factors influencing microbial pathogenicity:Portals of Entry Portal of entry: route for pathogens to gain entry into host • Mucous membranes • GI tract, respiratory tract, genitourinary tract • Skin (Intact) • Hair follicles, sweat gland ducts • Parenteral route • Microbe deposition when barriers are penetrated (punctures, wounds, bites) • Some microbes have preferred portals of entry

4. Factors influencing microbial pathogenicity:Portals of entry

5. Factors influencing microbial pathogenicity:Numbers of Invading Microbes Bacillus anthracis: • The likelihood of disease development increases as the number of invading microbes increases • ID50: Dose required to infect 50% of the test population • LD50: Lethal dose (of a toxin) for 50% of the test population *Easiest to acquire *Most potent toxin

6. Factors influencing microbial pathogenicity:Adherence/Attachment • Direct interactions between microbial adhesin proteins and host cell receptor proteins • Adhesins: components of microbial extracellular structures (capsule/glycocalyx, fimbriae, flagella) Figure 15.1

7. Factors influencing microbial pathogenicity:Adherence/Attachment • Biofilms are another type of substrate for attachment for some microbes • Indirect interactions between microbe and host • Bacteria adhere to host cell surface and secrete sticky glycocalyx, to which more microbes can attach • Concentrate nutrients, provide protection for bacteria • Dental plaques • Biofilms are estimated to be involved in at least 65% of all bacterial infections in humans http://webs.wichita.edu

8. http://webs.wichita.edu/ Biofilm on a catheter

9. Microbial Mechanisms for Penetrating Host Defenses • Impairment of phagocytosis (by host cells) • Cell wall components (i.e. mycolic acid) • Capsules B. anthracis with capsules surrounding a macrophage http://www.stemworks.org/anthrax/anthraxmicrographs.html

10. Microbial Mechanisms for Penetrating Host Defenses • Impairment of phagocytosis • Disguises • Antigenic variation: altering surface antigens so host antibody responses will be unsuccessful • Where have we seen this before? • Penetration into host cell • Some bacteria can move and multiply within host cells • Host cells can be microbial hideouts Trypanosoma brucei

11. Figure 22.5

12. Bacterial Mechanisms of Host Cell Damage • Using host cell’s nutrients • Siderophores: secreted bacterial proteins that collect host’s irondepletion of host iron stores • Direct damage to host cells • Plasma membrane damage from bacterial penetration • Bacterial waste products • Host cell rupture (excessive bacterial multiplication) • Toxin production

13. Bacterial mechanisms of host cell damage:Toxins • Toxins: poisons produced by some microorganisms • Two types of toxins: • Exotoxins (proteins secreted by bacteria) • Endotoxins (within bacterial cell walls)

14. Bacterial mechanisms of host cell damage:Exotoxins • Protein products of bacterial cells • Secreted from bacterial cell • Gram-positive or Gram-negative cells • Proteins (sometimes enzymes) • Typically low LD50 • Three types: • Membrane-disrupting toxins • Superantigens • A-B toxins Figure 15.4a

15. Bacterial mechanisms of host cell damage:Exotoxins: Membrane-disrupting toxins • Membrane-disrupting toxins • Lyse host’s cells by: • Making protein channels in the plasma membrane • Disrupting phospholipid bilayer • Exotoxin from C. difficile

16. Bacterial mechanisms of host cell damage: Exotoxins: Superantigens • Superantigens • Overstimulation of the host immune response • Cause an intense immune response due to release of cytokines from host cells • Fever, nausea, vomiting, diarrhea, shock, death • Toxic shock syndrome (TSS): toxin produced by a strain of S. aureus

17. Bacterial mechanisms of host cell damage:Exotoxins: A-B toxins • A-B toxins • Cholera toxin http://cmgm.stanford.edu/theriot/movies.htm#Primetime Figure 15.5

18. Bacterial exotoxins:Botulism • Clostridium botulinum • Endospore-forming, obligate anaerobe • Found in soil, freshwater sediments • Intoxication due to ingestion of botulinum toxin • A-B neurotoxin • Most potent natural toxin • Ingestion of endospores by adults usually not harmful • Botulinum toxin blocks release of a neurotransmitter at the neuromuscular junction • Loss of muscle movement (flaccid paralysis) • Death due to respiratory and cardiac failure

19. Bacterial exotoxins:Botulism • Treatment: supportive care and antitoxin • Slow recovery; nerve endings must regenerate • Infant botulism results from C. botulinum growing in intestines • Endospores germinate in digestive tract • Infants don’t have sufficient normal microbiota to outcompete C. botulinum • Prevention: • Proper canning • Infants less than one year old should not ingest honey

20. Bacterial mechanisms of host cell damage:Endotoxin • Lipid component of lipopolysaccharide portion of outer membrane of gram-negative bacteria • Released during bacterial cell death and multiplication Figure 15.4b

21. Bacterial mechanisms of host cell damage:Endotoxin • Endotoxin release • Fever • Blood clots • Septic shock

22. Sepsis and Septic Shock • Normally, no bacteria in our blood • But, if they overcome our defenses and gain access to our blood, they may undergo uncontrolled proliferation • Sepsis: infection of the blood with pathogens • Bacteremia: presence and proliferation of bacteria in blood • Shock: life-threatening decrease in blood pressure • Septic shock: shock caused by sepsis (50% mortality) • Low blood pressure is uncontrollable • Dysfunction of at least one organ

23. Sepsis:Gram-negative Sepsis • Gram-negative Septic Shock • Endotoxins trigger blood pressure decrease • Decreased blood flowimbalance between oxygen delivery and consumption • Initial symptoms are nonspecific and do not cause alarm • Antibiotics may arrest the progression, but are rarely given at such an early stage • Progression to lethal stages is rapid, nearly impossible to treat • Antibiotics at later stages can worsen condition by killing bacteria • Eventually leads to multiple organ failure

24. Sepsis:Gram-positive Sepsis • Often due to invasive hospital procedures that allow Gram-positive pathogens to enter the bloodstream (i.e. nosocomial) • Staphylococcus aureus • Staphylococcal toxin causes toxic shock syndrome • Superantigen exotoxin: causes release of fluids from capillarieslower blood pressure, shock • Streptococcus pyogenes • Common cause of puerperal sepsis (childbirth fever) • Transmitted to birthing mother by physicians/ midwives • Superantigen exotoxin: damage to blood capillaries • Uterine infectionperitonitissepsis

25. Portals of Exit • Generally same portal used for entry • Respiratory tract • Coughing, sneezing • Gastrointestinal tract • Feces, saliva • Genitourinary tract • Urine, vaginal secretions • Skin (wounds) • Blood • Biting arthropods, needles/syringes