5. Virulence Factors Flashcards
Terminology
• ____: The ability of a bacterium to cause infection
• ____: A bacterial strategy or product that is connected with their ability to cause disease
○ Will differ from bacteria to bacteria
§ There can be similar mechanisms however
virulence/pathogenicity
virulence factor
Virulence Factors • \_\_\_\_ and colonization • Invasion of \_\_\_\_ and tissues • Avoidance of \_\_\_\_ mechanisms • \_\_\_\_
adherence
host cells
host defense
toxin
Virulence Factors: Adherence and Colonization
• Two types of bacterial adherence mechanisms:
○ Pili
§ Protein-____ structure
§ Binds to the host ____ connected to the host cell membrane
○ Afimbrial adhesin
§ Binds to the host cell surface protein or ____
• Will involve an adhesin on the ____ and a receptor on the ____ tissue
carbohydrate glycolipid/glycoprotein cell carbohydrate bacteria host
P Pili
• Responsible for adherence of ____ to Urothelial Cells
○ An inhibitor will prevent them from binding
• Uropathogenic E. coli (UPEC): Cause ____ tract infections
• Bind receptors containing ____
○ Urinary tract is rich in galactose along with RBCs
• Receptors containing galactose are considered ____
○ Meaning they’re susceptible to ____ and the corresponding diseases
○ P Negative individuals have receptors that lack galactose meaning UPEC can’t bind –> Immune to ____ and they’re corresponding diseases
UPEC urinary galactose p positive UPEC UPEC
Adhesins Produced by B. pertussis
• Filamentous Hemagglutinin (Fha): ____ kDa protein that forms ____structures on the cell surface
○ Epithelial Cells –> binds to ____on their surface
○ Monocytes –> binds to ____ on their surface
• Pertussis Toxin (Ptx): \_\_\_\_ kDa hexamer that binds to \_\_\_\_ on cell surfaces ○ 2 forms: § One is \_\_\_\_ § The other stays in the \_\_\_\_ and will stay in the cell membrane acting as a receptor • Will cause pertussis and \_\_\_\_ cough
220
filamentous
glycolipids
integrin CR3
105 glycolipids released cell membrane whooping
Stages of Interaction of N. gonorrhoeae
1. Initial attachment
○ Using ____
2. Intimate association and phagocytosis
○ Use of ____ (Opa) protein
3. Prevention of phagolysosome formation
○ ____ prevents phagolysosome formation and thus degradation
pilli
P.II
P.I
Virulence Factors: Invasion of Host Cells and Tissues
• Entry into non-phagocytic cells: ○ High affinity interaction between the bacterial ligand and the host receptor § "\_\_\_\_" mechanism □ Yersinia: ® Only one protein on the surface called \_\_\_\_ ◊ Will interact with an \_\_\_\_ on the surface of the host cell ○ Due to signaling and modulating host cell cytoskeletal components § "\_\_\_\_" mechanism –> triggers a signal transduction mechanism to get inside the cell □ Salmonella: ® Binds to \_\_\_\_ receptor on the host cell and will release a signal, \_\_\_\_, that will rearrange the host cell's \_\_\_\_ ton bring in the bacteria • Entry into phagocytic cells: ○ By special mechanisms of control of \_\_\_\_ environments § Seen with \_\_\_\_
zipper
invasin
integrin
trigger
EGFR
MAPK
cytoskeleton
intracellular
mycobacterium tuberculosis
Virulence Factors: Avoidance of Host Defense Mechanisms
Anti-phagocytic mechanisms:
• Capsules as virulence factors
○ Includes:
§ ____
§ H. influenzae
§ ____
○ The bacteria produce a thick layer of ____ sugar –> prevents phagocytosis
§ Makes the capsule ____ and unable to be endocytosed by macrophages or PMNs
○ Bacteria without the capsule typically don’t cause disease since they can be ____
• Enzymes that are capable of lysing phagocytic cells ○ S. pyogenes –> \_\_\_\_ that will lyse \_\_\_\_ and \_\_\_\_by different mechanisms § Can insert into the \_\_\_\_ membrane freeing the bacteria • Protein A ○ \_\_\_\_ and Staphylococci • M Protein ○ \_\_\_\_ • Escape into the \_\_\_\_ inhibiting the fusion of the phagosome and lysosome preventing phagolysosome formation, and being able to resist lysosomal enzymes and oxidative killing: ○ \_\_\_\_
N. meningitidis
S. pneumoniae
hexose
hydrophilic
phagocytosed
streptolysin
WBC
RBC
lysosome
streptococci
streptococcus pyogenes
cytoplasm
m. tuberculosis
Examples of RBC Lysis
• ____-hemolysis is more virulent than gamma and alpha
○ Beta-hemolysis will cause ____
beta
disease
S. pyogenes M Protein
• M protein prevents the binding of ____ in the bloodstream
○ Preventing ____ activation allows for the survival of the bacteria
§ PMNs and macrophages cannot recognize the bacteria
○ Recruits ____ that will destroy C3b
C3b
complement
serum factor H
Ag Variation
• By altering ____, bacteria will be able to produce virulence factors that won’t be recognized by the immune system
• Bacteria that can do this have a high ____
antigenic expression
antigenic profile
Superantigens
• An Ag that interacts with ____ and other ____ resulting in ____ T Cell activation
○ Massive release of ____ and ____ activation
MHC Class II T cell receptors non-specific cytokines polyclonal T cell
Virulence Factors: Toxins
• Can work in ____ doses and be incredibly lethal
Types of toxins:
• Block host cell protein synthesis
○ ____ toxin
§ Modifies the protein ____ (elongation step of translation) preventing protein ____
• Hijacking host cell signal transduction
○ ____ toxin
§ Modifies ____ binding proteins
• Circumventing host immune defense
○ Toxic Shock Syndrome (TSS) toxin as a superantigen by ____
low diphtheria E2 translation cholera GDP S. aureus
Two Types of Bacterial Toxin
• ____: Proteins produced by bacteria that are usually secreted into the surrounding medium
• Endotoxins: ____ of the outer membrane of Gram Negative bacteria
○ Trigger localized inflammation
○ Can cause a systemic reaction if it reaches the ____ when the cells are lysed releasing LPS
exotoxin
LPS
BS
Examples of Bacterial Exotoxins
A-B Types:
• Share similar structures and thus functions
• Simple A-B Toxin: Polypeptide cleaved in half, but still linked at a disulfide bond into two different components
○ B Portion: N terminal unit that mediates binding of the ____ to the cell surface
○ A Portion: C terminal unit that is the ____ part
§ Majority are ____ enzymes that get transferred to the target protein
1. Diphtheria Toxin: • Produced by C. \_\_\_\_ • ADP-ribosylates host \_\_\_\_ preventing the elongation step of translation • Causes: ○ Diphtheria
2. Pertussis Toxin: • Produced by B. pertussis • ADP-ribosylates a host \_\_\_\_ protein –> \_\_\_\_ the activity • Causes: ○ \_\_\_\_ cough
3. Cholera Toxin: • Produced by V. cholerae • ADP-ribosylates a host \_\_\_\_ protein –> \_\_\_\_ the activity • Causes: ○ Cholera
4. Shiga Toxin: • Produced by Shigella dysenteriae • Cleaves host cell \_\_\_\_ • Causes: ○ Shigella
Superantigens: 1. Toxic Shock Syndrome (TSS) Toxin: • Produced by \_\_\_\_ • Causes: ○ \_\_\_\_ shock syndrome
toxin
toxic
ADP-ribosylate
diphtheria
EF2
G
decreases
whooping
G
increases
rRNA
S. aureus
Toxic shock
Structure of LPS
• O Ag:
○ Faces the ____
• Core Polysaccharide:
○ Links the O Ag and the ____ components
• Lipid A:
○ Embedded within the ____
○ This causes ____ when released from the cell wall and interacts with LPS Binding Protein
§ LPS-LPS Binding Protein complex will bind to ____ receptors on macrophages:
□ Release of ____ can cause endothelial damage via:
® Activation of the ____
® Activation of the ____
® Production of ____ and ____
environment
lipid A
cell wall
toxicity
CD14 cytokines coagulation cascade complement cascade prostaglandins leukotrienes
Genetic Determinants of Microbial Pathogenicity
• Isolating a gene for \_\_\_\_ can give E. coli the ability to invade a host cell ○ Example of the relationship between genes and virulence factors and how manipulation can lead to bacteria acquiring \_\_\_\_ they normally lack
invasin
virulence factors
Extrachromosomal Determinants of Pathogenicity
Plasmid-Encoded
• Plasmids can carry \_\_\_\_ genes too and can make \_\_\_\_ bacteria pathogenic • Enterotoxigenic E. coli: ○ Heat-labile and heat-stabile enterotoxins: § LT § ST ○ Adhesins CFA1/2 ○ Causes watery diarrhea via: 1st. Colonization of the \_\_\_\_ 2nd.\_\_\_\_ production
• Shigella species: ○ Gene products involved in invasion are all located close to each other on the \_\_\_\_ • Bacillus anthracis: ○ \_\_\_\_ factor ○ Lethal factor ○ \_\_\_\_ • Clostridium tetani: ○ \_\_\_\_ Bacteriophage-Encoded • Corynebacterium diphtheriae: ○ \_\_\_\_ toxin • Streptococcus pyogenes: ○ \_\_\_\_ toxin • Clostridium botulinum: ○ \_\_\_\_ • Enterohemorrhagic E. coli: ○ \_\_\_\_-like toxin (SLT)
antibiotic resistance
commenssal
SI
toxin
plasmid
edema
protective Ag
neurotoxin
diphtheria
erythrogenic
neurotoxin
shiga
• These types have become pathogenic via ____ transfer
○ Plasmids from shigella encoding Invasin are now in ____
NEED TO LOOK AT TWO PRIOR SLIDES!
plasmid
E. coli
Gene for Cholera Toxin
• The virulent genes tend to be arranged ____ to each other
• ____: Enzyme that promotes recombination of genes
• Will see ____ sequences like this when bacteriophages insert their genome into cells
closer
recombinase
repeated
Pathogenicity Islands
• Units of ____ genes organized together on a chromosome
○ These sequences are unique in ____ bacteria
• Will have a different and higher ____ DNA content
• ____ (enteropathogenic e coli) has a 35KB island and in the same position as UPEC (urinary pathogenic e
coli) in the same location there is a 70kb unit that code for urinary tract infections
• These segments do not exist in the ____ e coli
• This suggests that if the bacteria acquires some DNA that is pathogenic can become EPEC or UPEC
• So these pathogenic islands are particular sequences in the genome island that encode for pathogenicity of
particular type
virulent
pathogenic
G-C
EPEC
commensa
• Many ____ carry pathogenicity islands in their genome
• Seen with phages that introduce virulence genes into ____ producing bacteria
○ Can produce the ____ for adhesion
People found evidence that bacteriophage carried the 70kb toxin element of cholera in their genome and based on that people can propose the model and originally V cholera is not pathogenetic and doesn’t produce toxin but the phage produced by other bacteria can bind to the pili of the cholera and inject the bacteriophage into the bacteria that integrates into the genome and now the bacteria can produce ____
bacteriphages
cholera
toxins
toxin
SLIDE CHOLERA GENE
• This is the gene associated with cholera toxin production and they have ____ and CTxB and found that they are in the same class as each other and there are genes next to these that produce other types of toxin and there is a ____ gene open reading frame that makes an enzyme called ____ for recombination
the whole thing is in a 7Kb that is a small fragment and there is also ____ sequence on either side that are similar because they are the ones that are used to promote the ____ of the genes into the chromosomes
• These structures were surprise to scientists because not chromosomal virulence genes and can be transferred from somewhere else like ____
CTxA
four
recombinase
repeated
integration
horizontally
CTX Locus in E Cholera Genome
- How does the alien DNA end up here?
- This is the ex
- Repeat sequence suggests the ____ is involved
bacteriophage
SHIGELLA VIRULENCE PLASMID SLIDE
All of these genes are carried in the same ____ and in the same small area (38Kb out of 220kb plasmid)
• This means that originally if there is one commensal bacteria they are able to become pathogenic by
acquirement once because of ____ that carries all of the virulent factors and also makes it very scary
because any A virulent glen can become a pathogenetic gene by acquiring a virulent gene
• When we use ____ we put pressure on the bacteria for those that are carrying these so promotes the
transmission of spread to from one bacteria to the other and help them survive
plasmid
plasmid
antibiotics
