Bacterial Pathogenesis I

Question 1

Horizontal Gene Transfer

Answer 1

Bacterial

1) transformation: pick up DNA from enviro, dead or alive and incur in own genome
2) transduction: phage transfer, can become resistant to antibiotics, can get rid of virulence factors, can occur between species
3) conjugation: cells conjoin and transfer plasmid

Question 2

Griffiths Experiment

Answer 2

1928

natural transformation of strep pneumoniae, two strains injected in mice, encapsulated s strain caused death, others didnt, heat killed strain did, showing DNA incoorperated into host genome

Question 3

Transformation

Answer 3

DNA taken up directly by cells, bacteria able to take up DNA are said to be competent

1) Naturally Competent: some bac express DNA uptake systems (bacillus subtilis and strep pneum)
2) some bac take up from same genus and require specific seq of incoming DNA ( H flu and Neisseria)
* most naturally competent bac take up linear DNA but not circular plasmids of phage DNA

Question 4

Transduction

Answer 4

***mediated by bacteriophages

chop up pieces of DNA and pick up pieces of host DNA by accident and inject into recipient cells

Viruses that replicate within bacteria

Found everywhere there are bacteria

Question 5

Phage Life Cycle

Answer 5

Lytic

Lysogenic

Question 6

Prophage

Answer 6

Can carry important fitness and virulence determinants because dont have many genes (empty space for more)

Question 7

Generalized Transducing Phage

Answer 7

Transfer their DNA from one bac to another during lytic phase

can accidentily include bac genome when assembling virus particles

Question 8

Specialized Transducing Phages

Answer 8

lytic and lysogenic phases

can move bacterial DNA that flanks phage attachment sites (specific DNA seq) when they excise their genome and exit the lysogenic phase

Question 9

Conjugation

Answer 9

Bac sex
F- is converted to F+ and can be incorporated into genome and becomes HFR high frequency recombinase and doesn’t just move plasma but parts of chromosomes so genes!

good method for exchanging large dna pieces

Question 10

Four Plasmid Types

Answer 10

1. Fertility F- plasmids
2. Col plasmids
3. Virulence plasmids
4. Resistance (R) plasmids

*Some plasmids (mobilisable, mob) can only be transferred by tagging along with other plasmids that contain tra genes.

Question 11

Fertility F-plasmids

Answer 11

contain tra genes for transfer. They are capable of conjugation and result in the expression of sex pili.

Question 12

Col plasmids

Answer 12

contain genes that code for bacteriocins (proteins that can kill other bacteria). Some are also toxic to host cells (genotoxins)

Question 13

Virulence plasmids

Answer 13

encode virulence factors, can convert a bacterium into a pathogen. (e.g. pathogenic Salmonella strains)

Question 14

Resistance (R) plasmids

Answer 14

contain genes that provide resistance against antibiotics or poisons. Historically known as R-factors, before the nature of plasmids was understood.

Question 15

R plasmid pLW1043

Answer 15

single plasmid can carry the genes to resist many diff antibiotics

resistant to staph aureus

Question 16

Transposons

Answer 16

jumping genes
DNA elements that move from one place in bac DNA to another

transfer genes to new location or disrupt genes when they insert

can carry virulence and antibiotic resistance genes

Question 17

Pathogenicity Islands

Answer 17

many virulence genes in compact distinct genomic islands (10-200kb)

acquired by HGT

different G+C% content than rest of bac chromosome

• good indicator for whether that DNA is native or was included

Question 18

EHEC

EPEC

Answer 18

enterohaemorrhagic E coli: get genes from phage not plasmid

enteropathogenic E coli: get it from plasmid

Question 19

Type III Secretion Systems (T3SS)

Answer 19

molecular syringes, effector cells directly injected into cells with little needle structures

Question 20

Factors Facilitating Bacterial Infection and Survival Within a Host

Answer 20

attachment to host cells and tissues with adhesins
evasion of innate and adaptive responses
acquisition of limiting nutrients, iron, AA
dissemination within a host and transmission to new hosts (breaking tissue barriers)
ability to outcompete commensals at many stages

Question 21

Bacterial Adherence Mechanisms

Answer 21

*essential for bac colonization of hosts and determine species specificity

1. Pili-dependent adhesion: (gram + and gram-), rod-like
   projection with adhesion
   exposed for interaction with
   host receptors
2. Pili-independent adhesion: bacterial surface structure
   that interacts with host
   receptor

*Attachment can trigger
bacterial and host signaling
pathways, internalization
and uptake of bacteria

Question 22

How do bacterial pathogens deal with host defenses?

Answer 22

Microbes bind phagocyte receptors, envelope and phagosome and microbe fuse with lysosome and NO and ROS kill phagocytosed microbe

Question 23

Evasion of Host Defenses

Answer 23

1. bac in extracellular enviro prevent uptake and destruction by phage
2. bac in host cells have factos that promote survival in inhospitbal location
3. ***some bac regulate virulence factor expression (facultative intracellular bacteria)

Question 24

Survival Strategies Extracellular Pathogens

Answer 24

Capsules: prevent complement or mask Cb3

Very antigenic surface exposed antigens, allows outgrowth of clones

Secrete mol that interfere with host defense

Question 25

Survival Strategies Intracellular Pathogens

Answer 25

ROS and NO - staph - salmonella Neutralize phagolysosomes contents Prevent phagolysosome fusion - legionella - mycobacterium Escape from phagosome - listeria - francisella - rickettsia

Question 26

Listeria monocytogenes

Answer 26

Gram + Facultative anaerobe listeriosis, 3rd death of foodborne paths Dole lettuce 12 dead PrfA Regulon Attachs enterocyes by InIA and InIB trigger actin reorganization and signaling cascade activation. These result in internalization of the bacteria by host cells that are not considered professional phagocytes.

Question 27

Nutritional Immunity

Answer 27

Limiting the establishment or growth of microbial pathogens within the host by restricting access to essential “nutrients”. • Metals/cations (e.g. Fe, Mn, Zn, Cu, Mo) • Amino Acids • Carbohydrates, other nutrients •O and other Alternate Electron Acceptors

Question 28

3 Ways to avoid amino acid starvation

Answer 28

1. carry amino acids or things to make AAs (m tuberculosis) 2. pump in AA from external enviro with ankB (L pneumophila) 3. reticulate bodies > abberent bodies (C. trachomatis

Question 29

Iron Battle

Answer 29

bac can make mol that binds iron for greater affinity than host or change shape of iron to bring back to cells

Question 30

Salmonella

Answer 30

1. Typhoid: enteric fever, ab pain, rash on neck 2. Non typhoid: gastroenteritis, ab pain, vomit dissemination across intestinal mucosa (peyers patches) PAI-encoded effectors trigger host mem ruffles that envelope and internalize bound bacteria Outcompetes commensals with help from the host, can derive a lot of energy, steals iron