Infection
Growth of microbes that are not normally present in the host (regardless of whether or not the host is harmed)
Disease
Damage or injury that impairs regular host functions
Pathogen
A microbe that is able to cause disease
Opportunistic pathogen
A microbe that causes disease only in the absence of normal host resistance
Examples of opportunistic pathogens
Streptococcus pneumoniae and E. coli
Streptococcus pneumoniae
Causes pneumonia in immunocompromised patients
E. coli
Causes urinary tract infection when bacteria from feces are moved into the urethra
Pathogenicity
The ability to cause disease
Virulence
The severity of the disease that is caused - often given as an LD50 value
LD50
Number of cells of a pathogen (or dose of a toxin) that will cause death in 50% of infected animals
LD50 of Streptococcus pneumoniae
50 cells
LD50 of Samonella enterica
5000 cells
Pathogenesis
The process by which a disease develops
Steps that lead to an infection and tissue damage
Virulence factors
Genetically encoded traits that contribute to a pathogen’s ability to cause disease
Adherence
Ability for a pathogen to stick to a surface and begin colonization
Non-covalent adherence example
Capsules and slime layers
Streptococcus mutans non-covalent adherence factors
Uses slime layer to stick to teeth and form a biofilm
Streptococcus pneumoniae non-covalent adherence factors
Uses capsule to stick to cells in the lungs
Also protects the cell from phagocytes
Adhesins
Specific surface molecules that allow selective adherence to particular cell types
Enterotoxigenic E. coli adherence factors
Produce fimbriae and can adhere specifically to cells in the small intestine
Neisseria gonorrhoeae produces what adherence factors
Fimbriae that allow it to attach to mucosal epithelial cells - retract to bring bacteria close to the membrane
Opa proteins
Specifically attach to certain receptors on the host cell
Invasiveness
The ability of a pathogen to enter into host cells or spread through tissues
Virulence factors that promote invasiveness
Siderophores, exoenzymes, invasins
Siderophores
Iron binding molecules
Siderophore mechanism
Host proteins transferrin and lactoferrin - sequester iron, making it unavailable for other microorganisms - limits the growth of invaiders
Siderophores rip iron out of tissues to be used by bacteria
Types of exoenzymes
Hyaluronidase Collagenase Proteases, nucleases, and lipases Fibrinolysin Coagulase
Hyaluronidase
Hydrolyzes hyaluronic acid (cement that holds animal cells together)
Allows pathogen to spread between cell
Collagenase
Degrades collagen
Allows pathogen to spread through tissues
Proteases, nucleases, and lipases
Degrade host macromolecules
Fibrnolysin
Dissolves fibrin clots
Example of fibrinolysin
Streptococcus pyogenes makes streptokinase
Coagulase
Induces fibrin clots
Example of coagulase
Staphylococcus aureus produces coagulase to protect it from phagocytes
Keeps staph infections localized
Invasins
Proteins that allow bacteria to invade and enter directly into host cells
Listeria monocytogenes
Non-lactic acid, non-spore forming psychrotolerant member of Firmicutes
Where is Listeria monocytogenes found?
Unpasteurized dairy products, improperly packaged processed meats
Listeria monocytogenes produce
Invasins that promote phagocytosis by macrophages
Hijacks the cytoskeleton to escape the phagolysosome
Spreads from cell to cell
Avoiding humoral immune response
Bacteremia
Bacteria in the blood
Can be carried to different organs and tissues
Septicemia
Bacteria multiplying in the blood (i.e., a blood borne systemic infection)
Septicemia can lead to
Sepsis - widespread systemic inflammation
Septic shock is caused by
Gram negative bacteria, gram positives: staphylococci and enterococci
Exotoxins
Proteins released by growing bacteria that inhibit host cell function (or kill host cells), usually heat labile, can be extremely toxic
Bacillus anthracis virulence factors
Capsules, exoenzymes, and the anthrax toxin
Anthrax toxin
Interferes with the immune response and kills macrophages
Categories of exotoxins
Cytoxins, AB toxins, superantigens
Cytoxins
Disrupt cytoplasmic membrane integrity - cell lysis and death
Examples of cytotoxins
Hemolysins, lecithinase or phospholipase, and leukocidins
Hemolysins
Lyse many cells (not just red blood cells)
What produces hemolysins?
Streptococcus pyogenes
Streptococcus pyogenes produces
Streptolysin
Streptolysin
Attacks sterols in the cell membrane
Lecithinase or phospholipase
Dissolves membrane lipids
Example of lecithinase or phospholipase
Clostridium perfringens - alpha toxin (gas gangrene)
Leukocidins
Destroy white blood cells
Example of leukocidins
Staphylococcus aureus - staphyloccal alpha toxin
Leukocidin mechanism
Toxin subunits insert into the membrane and oligomerize to form a heptamer
Heptamer
A membrane spanning pore
Cell contents leak out and the cell dies
AB toxin is made of
Active subunit and binding subunit
Example of AB toxin
Diphtheria toxin
What produces diphtheria toxin?
Corynebacterium diphtheriae
Diphtheria toxin mechanism
Subunit B - specifically binds to a protein on animal cells
Subunit A - then moves across the membrane (interferes with protein synthesis)
Where is the gene for the diphtheria toxin?
On a virus, not on the chromosome
Other AB toxin
Tetanus, botulism, and cholera toxins
Super antigens
Activate T-cells to elicit an extreme immune response
Bind to MHC molecules TCRs outside the antigen binding site
Bridge the gap and mimic proper antigen
What do superantigens activate?
Huge number of T cells
T cells produce
Cytokines
Cytokine reaction
Extreme immune response
Extreme fever, systemic inflammation, shock, death
Example of superantigen
Staphylococcus aureus’ toxin shock syndrome toxin
Endotoxins
Lipopolysaccharide from the Gram negative outer membrane
Toxic part of endotoxin
Lipid A
Lipid A is released
When cells die
Which is more toxic: exotoxin or endotoxin
Exotoxins
Example of endotoxin
Samonellosis
Gram negative sepsis
Samonellosis mechanism
Colonizes the intestine - multiply to a huge number of bacteria
As bacteria die, they release endotoxin
Symptoms of Samonella
Fever, diarrhea, generalized inflammation
Gram negative sepsis
Gram negative bacteria multiply in the blood
Killed by immune system, releasing endotoxin
Massive inflammation leads to septic shock and death