Bacterial Pathogenesis

Side effect of heat labile toxin

(AC=> cAMP) watery diarrhea

Catalase positive organisms

*CATS* *N*eed *PLACESS* to *B*elch their *H*airballs *CATS* = catalase *N*ocardia *P*seudomonas *L*isteria *A*spergillus *C*andida *E* coli *S*taphylococci *S*erratia *B* cepacia *H* pylori

Urease positive organisms

*P*ee *CHUNKSS* *P*roteus *C*ryptococcus *H* pylori *U*reaplasma *N*ocardia *K*lebsiella *S* epidermidis *S* saprophyticus

Diphtheria toxin

- Made by Corynebacterium diphtheriae - Ribosylates elongation factor 2 - Blocks ribosome function; cell dies - Forms pseudomembrane over trachea

IL-1

-Secreted by macrophages -Also called osteoclast-activating factor. Causes fever, acute inflammation. -Activates endothelium to express adhesion molecules. -Induces chemokine secretion to recruit WBCs.

IL-6

-Secreted by macrophages -Causes fever and stimulates production of acute- phase proteins.

pyocyanin

-produces a blue-green pus. Produces exo- and endotoxins; grows in biofilms

A-B exotoxins

A - enzymatic component - Attacks cell B - Binds the toxin to host cell receptor (glycoprotein or glycolipid). After binding (B); A is transported into cell

Lethal factor (LF)

A component of anthrax toxin that cleaves host protein kinases.

Edema factor (EF)

A component of anthrax toxin with adenylate cyclase activity.

lipid A

A component of the gram-negative outer membrane; endotoxin

Endotoxins

A toxic component of the outer membrane of certain gram-negative bacteria that is released only when the bacteria die.

___mimics adenylate cyclase=> increase cAMp, responsible for characteristic edematous borders of black eschar in cutaneous anthrax

Anthrax toxin

____ is attached to the core and extends away from bacteria

Antigen O

Core polysaccharide

Attached to lipid A and contains unusual sugars. Its role is structural-- to provide stability.

how can we kill spores?

Autoclave Steaming at 121C for 15 mins Hydrogen peroxide and iodine based agents

Examples of spore forming bacteria

B anthracis (anthrax), B cereus (food poisoning), C botulinum (botulism), C difficile (pseudomembranous colitis), C perfringens (gas gangrene), C tetani (tetanus).

Encapsulated bacteria

Bacteria that possess thick carbohydrate coats that protect them from phagocytosis. Encapsulated bacteria cause extracellular infections and can be dealt with by phagocytes only if the bacteria are first coated with antibody and complement.

toxins that increase cAMP include

Bacteria thatincrease cAMP include Cholera, Anthracis, Pertussis, E coli; "Increase cAMP with CAPE

_______ over-activates AC=> increase cAMp by permanently activating Gs subunit causes Voluminous "rice-water" diarrhea

Cholera toxin

Diphtheria toxin inhibits protein synthesis and is made by

Corynebacterium diptheria

Transduction in bacteria

DNA is transferred from a donor cell to a recipient via a bacteriophage

_____ inactivation of EF-2 (elongation factor 2) sen with pharngitits w/ pseudomembranes and sever lymphdenopathy (bulls neck), myocarditis

Diphtheria toxin

Heat Labile toxin "LT" is produced by

ETEC and also B. cereus

What are endotoxins

Endotoxin, also known as lipid A, is released from the cell wall of Gram-negative bacteria and can cause systemic shock and other fatal effects.

What bacteria participate in transposition

Enterococcus to S aureus

IgA protease

Enzyme that cleaves IgA. Secreted by S. pneumoniae, H. influenzae type B, and Neisseria (SHiN) in order to colonize respiratory mucosa.

_______cross-linking of beta region of TCR, to MHC II, on APCS=> overwhelming IL-1/2 and IFN-y and TNF-alpha+> shock, produces scarlet fever

Erythrogenic exotoxin A

_______is produced by pseudomonas aeruginosa, it inhibits EF2, inhibiting protein synthesis, causes host cell death

Exotoxin A

pseudomonas aeruginosa

Exotoxin A=> stop protein synthesis=> inhib EF-2, host cell death

Hfr x F- Conjugation

F+ plasmid can become incorporated into bacterial chromosomal DNA, now termed Hfr cell. Replication of incoporated plasmid DNA may include some flanking chromosomal DNA. Transfer of plasmid and chromosomal genes.

F+ plasmid contains genes required for sex pilus and conjugation. Bacteria without this plasmid are termed F-. Sex pilus on F+ bacterium contacts F− bacterium. A single strand of plasmid DNA is transferred across the conjugal bridge ("mating bridge"). No transfer of chromosomal DNA.

F+ x F- conjugation

Genes for the following 5 bacterial toxins are encoded in a lysogenic phage: specialized transduction

Group A strep erythrogenic toxin, Botulinum toxin, Cholera toxin, Diphtheria toxin, Shiga toxin.

Anthrax toxin

Has two A subunits called Edema factor and Lethal Factor The B subunit is called Protective Antigen. Edema factor causes fluid loss to extracellular spaces similar to Bordetella. Lethal Factor destroys regulatory cascades crippling the immune response.

______ over-activates AC=> increase cAMP=> increase Cl secretion in gut and H2O efflux

Heat Labile toxin

____overactivate GC=> increase cGMP=? decrease resorption of NaCl and H2O in the gut

Heat Stable toxin

________ protein may loss its structure as it unfolds at high temperatures

Heat labile

Macrophage activation leads to

Il-1/6 => Fever TNF-a=> hypotension NO=> hypotension

O antigen

LPS

______ is part of the gram negative outer membrane and heat stable

LPS

what are the three structural components of LPS

Lipid A, core polysaccharide and O antigen

_____Helps prevent phagocytosis. Expressed by group A streptococci. Sequence homology with human tropomyosin and myosin (molecular mimicry); possibly underlies the autoimmune response seen in acute rheumatic fever.

M Protein

LOS is present in ______ species, due to the lack of it, this species is more susceptible to complement lysis via the host

Neisseria

C5a

Neutrophil chemotaxis Upregulate integrin Histamine release: hypotension and edema

____inhibits phagocytic ability, inactivates Gi=> increase AC=> increase cAMP=>Whooping cough—child coughs on expiration and "whoops" on inspiration; can cause "100-day cough" in adults

Pertussis toxin

_____ finds to Fc region of IgG preventing phagocytosis and opsonization, found on Staph aureus

Protein A

What are ureas positive bacteria?

Proteus, Cryptococcus, H.pylor, ureaplasma, nocardia, klebisella, s epidermidis, s saprophyticus

F' conjugation

Result when the F factor incorrectly leaves the host chromosome Some of the F factor is left behind in the host chromosome Some host genes have been removed along with some of the F factor these genes can be transferred to a second host cell by conjugation

in vivo biofilm- producing bacteria

S epidermidis - Catheter and prosthetic device infections Viridans streptococci (S mutans, S sanguinis) - Dental plaques, infective endocarditis P aeruginosa - Respiratory tree colonization in patients with cystic fibrosis, ventilator-associated pneumonia. Contact lens-associated keratitis. Nontypeable (unencapsulated) H influenzae - Otitis media

What bacteria use transformation?

S pneumoniae, H influenzae type b, and Neisseria (SHiN).

TSST-1

S. aureus SuperAg that causes toxic shock syndrome (fever, rash, shock). heat stable

_______ inactivates 60s ribosome by removing adenine from rRNA=> stoping protein synthesis

Shiga toxin

Shiga toxin

Shigella, and E. coli O157:H7 Cleaves host cell rRNA (inactivates 60S ribosome) Enhances cytokine release, causing HUS

Encapsulated bacteria examples

Strep pneumo Neisseria meningitides Klebsiella pnemoniae Salmonella typhi H Flu Hib

Erythrogenic exotoxin A

Strep pyogenes

____ protein that degrades cell membrane, strep Pyogenes makes it, lyses RBCs, contributes to B-hemolysis, used to diagnose rheumatic fever

Streptolysin O

NAM and NAG

The cell walls of bacteria are a polymer of short peptides and repeating chains of:

_____Cross-links β region of TCR to MHC class II on APCs outside of the antigen binding site overwhelming release of IL-1, IL-2, IFN-γ, and TNF-α=> shock

Toxic shock syndrome toxin

______A "jumping" process involving a transposon (specialized segment of DNA), which can copy and excise itself and then insert into the same DNA molecule or an unrelated DNA

Transposition

_____hydrolyzes urea to release ammonia and CO2=> increasepH.

Urease

A exotoxin

a toxin released by a living bacterial cell into its surroundings. (attacksm active)

___lyse cell membrane, Phospholipase (lecithinase) that degrades tissue and cell membranes, degradation of phsopholipids-> gas gangrene, double hemolysis on blood agar

alpha toxin

Viridans streptococci

are normal inhabitants of the oral cavity and are a cause of transeint bactermia after dental procedures. In patients with pre-existing valvular lesions, viridans streptococci can adhere to fibrin-platelet aggregates through dextrans to establish infection that leads to endocarditis Biofilm

B exotoxin

binding, it binds to a specific receptor molecule on the surface of the host cell, so that the A component can be moved across the membrane

P. aeurginosa produces _____ colored pigents

blue-green pigment (pyocyanin and pyoverdin)

S epidermidis can produce a biofilm, it is caused by

catheter and prosthetic devices infections

alpha toxin

causes RBC rupture, edema, and tissue destruction Double hemolysis

Bordetella pertussis

causes whooping cough, inhibits GI subunit for good, leading to increase in cAMP

Where are endotoxins found?

cell wall of gram negative bacteria

molecular mimicry

close resemblance between foreign antigen and self-antigen

toxic shock syndrome (TSS)

fever, rash, shock; other toxins cause scalded skin syndrome (exfoliative toxin) and food poisoning (heat-stable enterotoxin)

Pyoverdin

fluorescent greenish color, produced by p. aeruginosa

C3a

functions of inflammation Histamine release and edema, hypotension

LPS found in outer membrane of ________(both cocci and rods). Composed of O-antigen + core polysaccharide + lipid A (the toxic component).

gram ⊝ bacteria

_____substance that maintains its form at high temperatures

heat stable

obligate intracellular pathogens rely on

host ATP

capsules serve as a

important microbial virulence factors interfere with phagocytosis by blocking attachment of phagocyte Toll-like receptors to microbial PAMPs antiphagocytic virulence factor

Spore forming bacteria ____metabolic activity and are resistant to heat and chemicals

lack metabolic activity

_____ basic component of LPS essential for bacterial viability, toxicity of gram negative bacteria, hydrophobic (inner)

lipid A

What are the three main effects of endotoxins?

macrophage activation (TLR4/CD14), complement activation, and tissue factor activation.

Catalase degrades H2O2 into H2O and bubbles of O before it can be converted to microbicidal products by the enzyme_________

myeloperoxidase

where are exotoxins located

outside the bacterial cell, released from living cells

Streptolysin O

oxygen labile

_____ is associated with infections of Respiratory tree colonization in patients with cystic fibrosis, ventilator-associated pneumonia Contact lens-associated keratitis causes biofilm formation

p. aeruginosa

What toxin ADP-ribosylates via Gi to increase cAMP?

pertussis toxin

Tissue factor activation

platelet plug formation

Heat stable toxin

poison that is not destroyed by heating ETEC

Lipoligosaccharide (LOS)

present Neisseria, species lacks o antigen portion of LPS and is readily shed from bacteria, more susceptible to host mediate lysis

Urease hydrolyzes ureato release ammonia and CO2=> increasepH. Predisposes to struvite (magnesium ammonium phosphate) stones, particularly _____

proteus

Serratia produces ____ pigment

red

obligate intracellular pathogens

require living host cells to grow and propagate

Antigen O provides the major basis for _______ schemes of gram-negative bacteria

serotyping

Some gram ⊕ bacteria can form _______ when nutrients are limited. Spores lack metabolic activity and are highly resistant to heat and chemicals. Core contains dipicolinic acid (responsible for heat resistance

spores

lipid A, core polysaccharide, O antigen

three domains of lipopolysaccharide

Exotoxins

toxic substances that bacteria secrete into their environment, can be found in gram negative and positive bacteria

_____A "packaging" error. Lytic phage infects bacterium, leading to cleavage of bacterial DNA. Parts of bacterial chromosomal DNA may become packaged in phage capsid. Phage infects another bacterium, transferring these genes.

transduction

Competent bacteria can bind and import short pieces of environmental naked bacterial chromosomal DNA (from bacterial cell lysis). The transfer and expression of newly transferred genes is called _______

transformation

Capsular polysaccharide + protein conjugate serves as an antigen in _______

vaccines

Actinomyces israelii—________, which are composed of filaments of bacteria

yellow "sulfur" granules