BACTERIAL MECHANISMS OF PATHOGENICITY Flashcards
Lesson 6
the ability to cause disease by overcoming host defenses
pathogenicity
the degree of pathogenicity
virulence
PORTALS OF ENTRY
Mucous Membranes
- respiratory tract
- gastrointestinal tract
- genitourinary tract
- conjunctiva
Skin
Parenteral Route
- epithelium lining the respiratory tract, GIT,GUT, and conjunctiva
- mostly through:
1. GIT
2. respiratory tract– easiest and most frequent
MUCOUS MEMBRANES
- unbroken skin – impenetrable by most microorganisms
- e.g.,:
- through openings in the skin e.g., hair follicles and sweat gland ducts
- hookworm –bore through intact skin
- fungi – grow on keratin in skin or infect skin itself
SKIN
- direct deposition into tissues beneath the skin or into mucous membranes
whenpenetrated orinjured - e.g., punctures, injections, bites, cuts, wounds, surgery, and splitting of the
skin or mucous membrane due to swelling or drying
PARENTERAL
NUMBER OF INVADING MICROBES
- ID50
- LD50
ADHERENCE FACTORS
Streptococcus mutans
Actinomyces
Enteropathogenic Escherichia coli
Neisseriae gonerrhoeae
Treponema pallidum
Staphylococcus aureus
Streptococcus pyogenes
– bind surface receptors (usually mannose) on the cells of certain host tissues
Adhesins/Ligands
converts fibrinogen to fibrin that coagulates the blood to protect bacteria from phagocytosis and defenses
e.g. Staphylococcus
Coagulase
breaks down fibrin and digests clots
- Fibrinolysin/streptokinase –produced by Streptococcus pyogenes
Kinase
hydrolyzes hyaluronic acid, which holds together cells in connective tissues
e.g. streptococci and Clostridium perfringens
Hyaluronidase
breaks down collagen in connective tissues
e.g. Clostridium perfringens
Collagenase
destroys IgA
e.g. Neisseria gonorrhoeae and Neisseria meningitidis
IgA protease
- prevents phagocytic cells from adhering to the bacterium
- can induce antibody production and subsequent opsonization
- Some Killers Have Pretty Nice Capsules
CAPSULE
- a heat-resistant and acid-resistant protein produced by Streptococcus pyogenes
- mediates attachment of bacterium to host epithelial cells and helps resist phagocytosis
M PROTEIN
- waxy lipid that makes up the cell wall of Mycobacterium tuberculosis
- resists digestion by phagocytes, and allow bacterial multiplication inside phagocytes
MYCOLIC ACID
an aggregate of interactive bacteria attached to a solid surface or to each other and
encased in an exopolysaccharide matrix
BIOFILMS
BIOFILMS
- Enhance adherence
- Resist disinfectants and antibiotics
- Resist phagocytosis
* Phagocytes do not move through
the viscous carbohydrates of biofilms.
* The EPS of Pseudomonas aeruginosa kills phagocytes. - Shield antigens
- process bywhich pathogenscanalter surfaceantigens
- By the time the body mounts an adaptive immune response against a
pathogen, the pathogen has already altered its antigens and is unaffected
by the antibodies. - e.g. Neisseria gonorrhoeae, Borrelia recurrentis
ANTIGENIC VARIATION
- M.tuberculosis, L. monocytogenes, Brucella species, Legionella species
- live and grow in the hostile environment within PMNs, macrophages, or
monocytes - may avoid entry into phagolysosomes and live within the cytosol of the
phagocyte - maypreventphagosome–lysosomefusionandlive within the phagosome
- may be resistant to lysosomal enzymes and survive within the
phagolysosome - can live within nonphagocytic cells
INTRACELLULAR PATHOGENICITY
- take the iron awayfromiron-transport proteins (e.g. lactoferrin, transferrin,
ferritin, hemoglobin) by binding the iron even more tightly - iron-siderophore complexes are taken up by siderophore receptors on the
bacterial surface into the bacterium
SIDEROPHORES: USING THE HOST’s
NUTRIENTS
- e.g., E. coli, Shigella, Salmonella, Neisseria gonorrhoeae
- can induce host epithelial cells to engulf them similarly to phagocytosis
- cause cells to rupture
DIRECT DAMAGE
- poisonous substances that are produced by certain microorganisms
- often the primary factor contributing to pathogenicity
TOXINS
capacity to produce toxins
Toxigenicity
presence of toxins in the blood
Toxemia
caused by the presence of a toxin; not by microbial growth
Intoxication
2 types of toxins:
- Endotoxins
- Exotoxins
- part of bacterial cells, not a metabolic product
- released during bacterial multiplication and when gram-(-) bacteria undergo lysis
- lipid A portion of LPS in the outer membrane
- producedbygram-(-) bacteria
- general and universal effects (fever, weakness, generalized aches, leukopenia,
hypoglycemia, disseminated intravascular coagulation [DIC], sometimes shock
andevendeath) - do not promote the formation of effective antitoxins (which actually enhance the
effect of toxins)
ENDOTOXINS
- a sensitive test to identify the presence of endotoxins in drugs, medical
devices, and body fluids - a.k.a. LimulusAmebocyte Lysate (LAL)Assay
- The hemolymph (blood) of the horseshoe crab, Limulus polyphemus,
contains white blood cells called amebocytes, which have large amounts
of aprotein (lysate) that causes clotting. - In the presence of endotoxin, amebocytes in the crab hemolymph lyse
andliberate clotting proteins. - Agel-clot (precipitate) is a positive test for the presence of endotoxin.
BACTERIAL ENDOTOXIN TEST
- producedinside a bacterium aspart of growth andmetabolism
- secreted into the outside medium orreleased following lysis
- proteins
- producedbygram-(+) orgram-(-) bacteria
- highly specific effects
- among the most lethal substances known
- soluble in body fluids and can easily diffuse into the blood and are rapidly
transported - carried by genes on bacterial plasmids or phages
EXOTOXINS
- E.g.,:
- Botulism
- Staphylococcal foodpoisoning
- Antitoxins– antibodies that provide immunity to exotoxins.
- Toxoids
- exotoxins inactivated by heat or by formaldehyde, iodine, or other
chemicals - used as vaccines to induce immunity (antitoxin production), but not cause
disease - e.g. diphtheria, tetanus
EXOTOXINS
NAMING EXOTOXINS
Based on type of cells attacked:
Based on disease caused:
Based on bacterial source:
TYPES OF EXOTOXINS
A-B TOXINS
MEMBRANE-DISRUPTING TOXINS
SUPERANTIGENS
- 2 polypeptides
- A: enzyme component (toxic)
- B: binding component
- e.g. Corynebacterium diphtheriae
A-B TOXINS
cause lysis of host cells by disrupting
their plasma membranes forms protein channels (e.g. Staphylococcus aureus) and
disrupts the phospholipid bilayer
(e.g. perfringens)
MEMBRANE DISRUPTING TOXINS
kill phagocytes by forming protein channels
Leukocidins
kill erythrocytes by forming protein channels
Hemolysins
produced by streptococci
Streptolysins
produced by Listerian monocytogens
Membrane-attack complexes (MAC’s)
- antigens that provoke a very intense immuneresponse
- bacterial proteins that combine with a protein on macrophages
- results in proliferation ofT cells and overproduction of cytokines
- produce S/Sx e.g.,: fever, nausea, vomiting, diarrhea, sometimes shock and even
death - e.g., staphylococcal enterotoxin, toxic shock syndrome toxin
SUPERANTIGENS
- Rfactors–resistance to antibiotics
- Virulence factors e.g., tetanus neurotoxin, heat-labile enterotoxin,
staphylococcal enterotoxin D, dextransucrase produced by Streptococcus
mutans, adhesins and coagulase produced by Staphylococcus aureus, and
fimbria of enteropathogenic strains of E. coli
PLASMIDS
