Bacterial Pathogenesis

Question 1

Pathogenic bacteria are clonal or non clonal?

Answer 1

1. clonal (virulence genes, isolated in pure culture)

Question 2

Can strains of the same species can have distinct phenotypes? Examples?

Answer 2

Yes, through selection (mutations present at low frequency, mutants selected bc growth advantage in particular conditions.

ex. tissue tropism: enteropathogenic vs. uropathogenic E. coli

Question 3

Immune selection

Answer 3

host immune response in relapsing fever is the driving force for antigenic variation Borrelia hermsii

Question 4

antibiotic resistance

Answer 4

• more commonly selected in population rather than individual
• inappropriate use of antibiotics in humans, or overuse of antibiotics in livestock

Question 5

What are Koch’s postulates for establishing the cause of an infectious disease?

Answer 5

1. Microorganisms found in all cases of the disease and in appropriate location
2. micro can be grown outside the hosr (in pure culture in vitro) for several generations
3. reinoculation of cultivated micro causes the disease
4. microor can be isolated from experimentally produced disease

Question 6

koch’s postulates requires culture and an experimental model. Which do not statisfy the postulates?

Answer 6

1. growth in vitro: some cannot be cultured
   - treponema pallidum (syphillis): use animal model
   - tropheryma whipplei (Whipple’s disease): identify by PCR

experimental infection: absence of animal model

2. neisseria gonorrhoeae: use human experimental model
3. polymicrobial infection

-

Question 7

Pathogenicity

Answer 7

1. transmissibility
2. production of toxins and enzymes
3. adherence to host cells
4. secretion of bacterial proteins into host cells
5. invasion of host tissue
6. survival inside host cells
7. evasion of host immune response
8. tissue damage from host immune response
9. requirement for iron
10. regulation of virulence factors
11. antibiotic resistance
12. mobile genetic elements

Question 8

Transmissibility: Why have clinical symptoms?

Answer 8

advantage of mild disease: survival of host enhnaces change of trnasmission

1. non-adapted host/pathogen: incidental infection of humans, often by zoonotic bacteria (ex. salmonella in poultry)
2. clinical symptoms that produce transmission (ex. vibro cholerae)
3. disease manifestatino that are due to host response to pathogen (ex. tissue scarring- chlamydia trachomatis)

Question 9

What are some clinical symptoms that promot transmission?

Answer 9

respiratory route: coughing, sneezing

Gastrointestinal: diarrhea

STI: genital dischare and genital ulcer

person-to-person transmissoin by direct contact: skin discharge

Question 10

Transmissibility: portal of entry

Answer 10

via mucous membrane

normal skin is good barrier vs abnormal skin (wounds, nbites, burns) & mucous membrane (chemotheraphy)

arthropod vectors

injection drug use

medial intervention: surgery, catheters

Question 11

Transmissibility: spread within the body

Answer 11

direct tissue spread

vascular

lymphatics

carriage w/in MO

ascending/descending spread within a tract

ex. respiratory intection- upper (bronchitis)–>lower (pneumonia) (Descending)

urinary tract infect- bladder (cystitis)–>kidney (pyelonephritis) (ascending)

genital tract infection- lower (cervicities)–>upper (pelvic inflammatory dx)(ascending)

Question 12

how do Extracellular bacteria cause disease?

Answer 12

cause disease via the effect of toxins and enzymes

Question 13

How do intraellular bacteria cause disease?

Answer 13

invade host cells. often cause of chronic infection

Question 14

Exotoxins

Answer 14

highly toxic proteins secreted by bacteria into extracellular envirn.

1. in a few cases performed toxin is ingested, but usually an active bacterial infection is required
2. may act locally or distant site.

Question 15

What are the subunits in exotoxins?

Answer 15

A: active subunit w/ specific toxin activity

B: binds to specific host cell receptor; involved in entry of exotoxin into cell

Question 16

Example of 2 subunit exotoxin?

Answer 16

1. corynebacterium diphtheriae (inhibition of protein sysnthesis)
2. vibro cholerae (inducers of cAMP-incresed secretion)
3. clostridium tetani (neurotoxin- block release of inhibitory transmitters, continuous excitatory)
4. Clostridium botulinum: (neurotoxin- block ach release)
5. Anthrax toxin *

Question 17

What is special about the 2 subunit anthrax toxin?

Answer 17

• 3 proteins make up 2 toxins
• “protective antigen” is the B subuit of each of the 2 toxins
• the A subunit for 2 toxins (a. edema factor: adenylate cyclase, b. lethal factor: kills cells)

Question 18

Superantigens. produced by?

Answer 18

some exotoxins are superantigens

produced by bacteria and viruses

• highly antigenic, heat lablile
• partially denatured by treatment w/ formalin, acid or heat–>toxoid (non-toxic but still antigenic- used for immunizations- diphtheria, tetanus toxoids

Question 19

what is the action of superantigens?

Answer 19

Polyclonal stimulation of subset of lymphocytes (tcells) to dicide and produce cytokines

ex. TSST-1, stre exotoxins, pyrogenic toxins- cause fever

Question 20

Endotoxin

Answer 20

LPS (in gram- cell wall, liberated when bacteria lyse)

Question 21

what is the mechanism of action for an endotoxin?

Answer 21

endotoxin in bloodstream–>binds to R on MO–>cytokine release (IL-1, TNFa)–>inflammatory & coagulation cascades

Question 22

Can gram + cuse septic shock without LPS?

Answer 22

yes, probably due to peptidoglycan, less potent than LPS

Question 23

What is the toxic moiety in LPS?

Answer 23

Lipid A

Question 24

what is the clinical effect of endotoxin?

Answer 24

fever and septic shock

-LPS not as toxic as exotoxin, less antigenic too, relatively heat stable

Question 25

Summary of Exotoxin vs Endotoxin

Answer 25

Question 26

What are some examples of enzymes?

Answer 26

may not be intrinsically toxic, but can cause tissue damage 1. hyaluronidase: degrades Hyaluronidase acid 2. streptokinase: fibriolysin 3. coagulase: coagualtes plasma 4. catalase: inhibits oxidative killing 5. cytolysins kill host cells: streptolysin S & O, Listeriolysin O

Question 27

how is Adherence to host cells mediated?

Answer 27

ahesions (bacteria) and host cells (receptors) -antibodies against the adhesion can block adhesion and protect host from infection

Question 28

How to bacterial cells physically attach?

Answer 28

binding by pili (aka fimbriae)- hairlike appendages that extend form bacterial surfaces

Question 29

Type III secretion of bacterial proteins

Answer 29

specialized system for secreting bacterial virulence proteins into host cells only pathogenic Gram - secreted proteins modulate host cell fxn

Question 30

what are the functions of the secreted bacterial proteins?

Answer 30

1. induce or prevent uptake by mammalian cells ex. induce uptake- bacteria invade mammalian cells. salmonella prevent uptake: prevent phagocytosis MO, yersinia 2. Induce of prevent death of mammalian cell ex. induce apoptosis in MO, yersinia ex. prevent apoptosis: intracellular bacteria, chlamydia

Question 31

Invasion of host cell

Answer 31

- Some bacteria can incduce their uptake by normally non-phagocytic cells - requires specific interaction btw baterial ligand and host cell receptor - involved actin cytoskeleton rearrangements - often involves Type III secretion system

Question 32

How do pathogens survive inside host cells?

Answer 32

Advantages of intracellular localization 1. nutrient rich envir 2. absence of competing microorg. 3. protected from humoral immune system ex. survucal inside phagolyso (coxiella), inhibition of phagolyso (chalmydia), escape into cytosol/actin based motility (listeria)

Question 33

What are some examples of antiphagocytic activity?

Answer 33

1. adsorb normal host component to surface of bacteria: staphylococcus aureus protein A binds IgG 2. Surface factors that inhibit phagocytosis - polyysacc capsule - m protein- group A strep - pili- neisseria gonorrhoeae 3. type III secreted proteins that prevent phagocytosis 4. kill phagocytic cell: group A streptococcal steptolysin

Question 34

evasion of host immune response: polysaccharide capsule

Answer 34

prevents complement deposistion and is poorly immunigenic - polysaccharide induces T cell-independent immune response ex. neisseria meningitidis, streptococcus pneumoniae, haemophilus influenzae poor immune response in children \<2yrs

Question 35

Are antibodies against capsular polysaccharide type specific or non specific?

Answer 35

specific, do not protect agaisnt diff types ex. penumococcal vaccine is directed against 23 capsular polysaccahride tyeps antibodies protect agsinst systemic infect not mucosal colonization

Question 36

What are some ways that pathogens evade host immune responses?

Answer 36

1. antiphagocytic activity 2. polysacc capsule 3. antigenic variation 4. IgA protease

Question 37

How do pathogens escape immune response via antigenic variation?

Answer 37

shift in the expression of surface antigens ex. niesseria gonorrhoeae: 3 surface molecules (lipooligosacc, pili, Opa proteins) can each be sweitch to diff antigenic forms ex. borrelia hermsii (relapsin fever): repertoire of variant surface antigen that is antigenically distinct

Question 38

How do pathogens evade for immune response via IgA protease?

Answer 38

cleaves IgA (mucosal immunity) ex. enzymes produced by: Neisseria gonorrhoeae, neisseria meningitidis, haemophilus influenzae, streptococcus pneumonia

Question 39

What are 4 types of tissue damage that is caused by the host immune response?

Answer 39

1. immune complex deposition - baterial antigen + Ab complement - post-streptococcal acute glomerulonephritis: deposition of immune complezes in glomeruli of kidney 2. molecular mimicry - post-streptococcal rheumatic fever is an autoimmune process w/ Ab against streptococcal antigen cross-rx againt host tissue 3. tissue damage and scarrying: chlamydis trachomatis 4. delayed type hypersensitivity: TB

Question 40

Where is most iron in the body?

Answer 40

intracellular: Hb and myoglobin

Question 41

Is most iron free?

Answer 41

very little iron is free. extracellular iron is bound to transferrin (in plasma) and lactoferrin (in milk and other secretions)

Question 42

What do bacteria use to capture iron?

Answer 42

siderophores ex. E.coli

Question 43

regulation of virulence factors

Answer 43

bacteria regulate the expression of virulence factors in response to environmental signals ex. temperature, ions availability, iron avaiability, etc

Question 44

What are 3 mechanism for antibiotic resistance?

Answer 44

1. inhibition of antibiotic 2. target side alteration 3. decreased intrabacterial accumulation of antibiotic

Question 45

explain the inhibition of antibiotic mechanism for ab resistance.

Answer 45

often by enzymatic hydrolysis of the ab ex. enteric gram - bacilli that produce b-lactamases

Question 46

explain target site alteration mech of ab resistance

Answer 46

decreases binding affinity of the ab for the target ex. penicillin-resistant strep penumoniae (altered PBP protein) ex. MRSA expressing altered PBP protein ex. Vancomycin resistance enterococcus expressing altered cell wall oligopeptide

Question 47

## Footnote explain how the decreased intrabacterial accumulation of abs is involved in the mech of ab resistance

Answer 47

- decreased outer membrane permeability - changes in porin channels - increased drug efflux: often results in multidrug resistance (pseudomonas aeruginosa uses all 3 of these mech to prevent accumulatin of ab)

Question 48

mobile genetic elements

Answer 48

allow acquisitio of genetic infro by horizontal transfer including virulence genes and ab resistance genes 1. plasmids- passed by conjugation, contain ab resistance genes 2. phages- bacteria infected by lytic phages or carry prphaes in the bacterial chr. (Ex. v. cholerae)

Question 49

examples of some cases in which only strains that have the prophage and its virulence genes cause specific disease

Answer 49