Lecture 5

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1
  is an important step in the process of infection
Adhesion is an important step in the process of infection
2
Microbe encounters a host and possesses mechanisms to survive in a particular  of
the body
Microbe encounters a host and possesses mechanisms to survive in a particular niche of
the body
3
Once the microbe begins successful   then it has colonized the tissues – this
process may involve invasion into tissues
Once the microbe begins successful replication then it has colonized the tissues – this
process may involve invasion into tissues
4
In an infection the host immunity may be interacting with the microbe but  have
yet to develop
In an infection the host immunity may be interacting with the microbe but symptoms have
yet to develop
5
As a consequence of microbial
colonization, mechanisms are
employed to maintain
colonization or invade tissues
which   tissue/cellular
functions or triggers  
immune reactivity =  
As a consequence of microbial
colonization, mechanisms are
employed to maintain
colonization or invade tissues
which impairs tissue/cellular
functions or triggers damaging
immune reactivity = DISEASE
6
Bacterial gain entry via   (Skin, mucus, ciliated epithelium, antibacterial
secretions)
Bacterial gain entry via natural defenses/ barriers (Skin, mucus, ciliated epithelium, antibacterial
secretions)
7
Non specific attractive forces that encount bacterium are 1.   2.   3.  
Non specific attractive forces that encount bacterium are 1. hydrophobic 2. electrostatic 3. atomic/molecular
8
Specific forces involve permanent formation of many specific lock and key bonds between complementary molecules on each cell surface ( ). Examples are the  /  and the   adhesions.
Specific forces involve permanent formation of many specific lock and key bonds between complementary molecules on each cell surface (ligands-adhesins). Examples are the pili/fimbriae and the afimbrial adhesions.
9
**TQ  and  are negatively charged and can recruit positively charged ions. It has some repelling effect on antibiotics, but mostly functions in  
**TQ TA and LTA are negatively charged and can recruit positively charged ions. It has some repelling effect on antibiotics, but mostly functions in adherence
10
  linked directly to the peptidoglycan layer
Teichoic acid linked directly to the peptidoglycan layer
11
 cid possess a transmembrane domain so anchored into the
bacterial cell membrane
Lipoteichoic acid possess a transmembrane domain so anchored into the
bacterial cell membrane
12
  are tightly associated polysacharides with the cell wall.
Capsules are tightly associated polysacharides with the cell wall.
13
What is the main function of a capsule? (The one he said would be on test) Secondary important function?
Prevent phagocytosis (main) and attachement
14
What is a slime layer?
Loosely associated  ,  , and   with the cell wall.
What is a slime layer?
Loosely associated glycoprotein, glycolipids, and polysaccharides with the cell wall.
15
What are the two important function of the slim layer?
1. Attachment
2. Biofilm formation
16
It is thought that up to  of bacterial species live in
communal associations or biofilms
It is thought that up to 99% of bacterial species live in
communal associations or biofilms
17
Biofilm
– collections of bacteria in a “multicellular” state
where survival requires   and
  between cells
Biofilm
– collections of bacteria in a “multicellular” state
where survival requires chemical communication and
cooperation between cells
18
Extracellular matrix forms composed of  ,  ,
 ,  ,  ,   – scaffold for biofilm
organization and signaling as well as regulate access by
environmental factors and antimicrobials
Extracellular matrix forms composed of glucans, fructans,
proteins, lipids, glycoproteins, DNA – scaffold for biofilm
organization and signaling as well as regulate access by
environmental factors and antimicrobials
19
  permits bacteria cell-to-cell communication
where bacteria coordinate the expression of certain genes in
response to signaling molecules released by the matrix
Quorum sensing permits bacteria cell-to-cell communication
where bacteria coordinate the expression of certain genes in
response to signaling molecules released by the matrix
20
During an infection pathogenic bacteria MUST
coordinate their virulence in order to be able to
establish a successful infection – controlled by
  released by the matrix
During an infection pathogenic bacteria MUST
coordinate their virulence in order to be able to
establish a successful infection – controlled by
autoinducers released by the matrix
21
When cell density in the biofilm is high –
  interact with colony bacteria to
promote virulence gene expression (and
  resistance factors)
When cell density in the biofilm is high –
autoinducers interact with colony bacteria to
promote virulence gene expression (and
antimicrobial resistance factors)
22
Colonization (  and  )
Colonization (adherence and replication)
23
Spreading Factors (production of  
Spreading Factors (production of invasins)
24
Access Nutrient Sources
(by   enzymes)
Access Nutrient Sources
(by degrading enzymes)
25
Toxins (  and  )
Toxins (exotoxins and endotoxins)
26
Hyaluronidase
• Enzyme that attacks the networks of   opening up the  
• Produced by  ,  ,  
Hyaluronidase
• Enzyme that attacks the networks of connective tissue opening up the extracellular matrix
• Produced by Streptococcus, Staphylococcus, Clostridium
27
Collagenase
• Enzyme that breaks down  , esp. in muscle tissues
• Produced by  
Collagenase
• Enzyme that breaks down collagen, esp. in muscle tissues
• Produced by Clostridium perfringens
28
Streptokinase and
Staphylokinase
• Enzymes that convert inactive   into , which digests
  and prevents clotting of blood
Streptokinase and
Staphylokinase
• Enzymes that convert inactive serum
plasminogen
into plasmin, which digests
fibrin and prevents clotting of blood
29
Streptokinase and
Staphylokinase are produced by   and  
Streptokinase and
Staphylokinase are produced by streptococcus and staphylococcus
30
 is needed for bacterial growth for respiration (electron transport), DNA synthesis, and free radical scaveging (antioxidant rxns)
Iron is needed for bacterial growth for respiration (electron transport), DNA synthesis, and free radical scaveging (antioxidant rxns)
31
Cytotoxins demagae host cells to release  
Cytotoxins demagae host cells to release ferritin
32
  lyses RBC to release hemoglobin
Hemolysin lyses RBC to release hemoglobin
33
Neutrophils release   from   granules
Neutrophils release lactoferrin from second degree granules
34
Transferrin is already in the  
Transferrin is already in the extracellular fluid
35
Bacteria use  to bind to form a complex
Bacteria use siderophore to bind to form a complex
36
Host   prevents siderophore from binding to its receptor
Host sideocalin (Sn) prevents siderophore from binding to its receptor
37
Bacteria counteracts by using   to prevent Sn from binding to siderophore
Bacteria counteracts by using stealth siderophore (SS) to prevent Sn from binding to siderophore
38
Enzymes that act in animal cell membranes:
o Direct insertion to form a pore for  
o Enzymatic attack on host cell  
(  or  ), which destabilizes
the membrane
Enzymes that act in animal cell membranes:
o Direct insertion to form a pore for cell lysis
o Enzymatic attack on host cell phospholipids
(lecithinases or phospholipases), which destabilizes
the membrane
39
Hemolysins
-  or  / 
-Produced by  (streptolysin) and
  (alpha toxin)
Hemolysins
-Pore-formers or phospholipases/lecithinases
-Produced by Streptococcus (streptolysin) and
Staphylococcus (alpha toxin)
40
Phospholipases
-Produced by   ( )
which hydrolyzes cell membrane  
Phospholipases
-Produced by Clostridium perfringens (alpha toxin)
which hydrolyzes cell membrane phospholipids
41
Lecithinases
- Produced by   which destroys
  (phosphotidylcholine) in membranes
Lecithinases
- Produced by Clostridium perfringens which destroys
lecithin (phosphotidylcholine) in membranes
42
 ,  ,  
Function in bacterial nutrition and metabolism (indirectly involved in invasion)
Proteases, Lipases, Nucleases
Function in bacterial nutrition and metabolism (indirectly involved in invasion)
43
Ig   lyse unwanted antibodies so bacteria can access host cells
Ig protreases lyse unwanted antibodies so bacteria can access host cells
44
 and  dissolve neutrophil extracellular traps (NETs) to escape
uptake (phagocytosis) by  
Nucleases and Catalases dissolve neutrophil extracellular traps (NETs) to escape
uptake (phagocytosis) by neutrophils
45
• Some peptidases lyse  
• Prevents detection and/or elimination by
host response
• EX –   and  peptidases
• Some peptidases lyse serum
complement factors

• Prevents detection and/or elimination by
host response
• EX – C3a and C5a peptidases
46
Exotoxins
• Produced by most bacteria
Exotoxins
• Produced by most Gram-positive bacteria
47
Exotoxin is usually main determinant of
 for those bacteria producing them
Exotoxin is usually main determinant of
virulence for those bacteria producing them
48
  are not required for pathogen growth
– Genes usually found on plasmids or encoded
by phage DNA
Exotoxins are not required for pathogen growth
– Genes usually found on plasmids or encoded
by phage DNA
49
Most exotoxins can be denatured by  ,
 , and  , have high  
and possess specificity of action
Most exotoxins can be denatured by heat,
acid, and enzymes, have high catalytic activity
and possess specificity of action
50
Most of these toxins are “strongly”  . Important because very stimulatory to   Good targets for  
Most of these toxins are “strongly” antigenic . Important because very stimulatory to immune response. Good targets for vaccines.
51
** TQ Exotosins are ab toxins. B part delievers active   to the cell. On endoytosis,   is released into cytoplasm.
** TQ Exotosins are ab toxins. B part delievers active subunit A to the cell. On endoytosis, subunit A is released into cytoplasm.
52
  are purposely produced to cause damage,   are NOT purposely produced to cause damage
Exotoxins are purposely produced to cause damage, endotoxins are NOT purposely produced to cause damage
53
Lipopolysaccharide (LPS) is a component of
Gram-  cell walls
Lipopolysaccharide (LPS) is a component of
Gram-negative cell walls
54
Lipopolysacchardies release endotoxins on ,  , and  
Lipopolysacchardies release endotoxins on autolysis, external lysis, and phagocytic digestion
55
Toxcity of the endotoxin lipopolysaccharide is due to  component
Toxcity of the endotoxin lipopolysaccharide is due to Lipid A component
56
The toxcitity associated with lipopolysaccahrides cause 750,000 cases of   each year, 30% mortality
The toxcitity associated with lipopolysaccahrides cause 750,000 cases of sepsis each year, 30% mortality
57
Heat stable (boiling 30 min has no effect) on lipopolysaccharides; must
treat with strong   agents (peroxide,
hypochlorite,…)
Heat stable (boiling 30 min has no effect) on lipopolysaccharides; must
treat with strong oxidizing agents (peroxide,
hypochlorite,…)
58
Lipopolysaccharides are mildly  . Antibodies recognize   regions, but not as strong as exotoxins
Lipopolysaccharides are mildly antigenic. Antibodies recognize O antigen regions, but not as strong as exotoxins
59
High levels of endotoxin =  
High levels of endotoxin = septic shock
60
Gram negative bacteria release endotoxins in into the blood spream that leads to   (  damage),  (  and  ), and activated   (decrease   and impair   exchange)
Gram negative bacteria release endotoxins in into the blood spream that leads to complement activation (lung tissue damage), clotting activated (clots and hemmorage), and activated macrophages (decrease blood pressure and impair O2/CO2 exchange)
61
While endotoxins come from gram   bacteria, exotoxins come from gram  bacteria
While endotoxins come from gram negative bacteria, exotoxins come from gram positive bacteria
62
While endotoxins use , exotoxins are made of 
While endotoxins use lipoplysaccharides, exotoxins are made of protein
63
While endotoxins are part of the  , exotoxins are  
While endotoxins are part of the outer membrane, exotoxins are extracellular
64
While endotoxins are  denatured by boiling, exotoxins are   denatured by by boining
While endotoxins are not denatured by boiling, exotoxins are usually denatured by by boining
65
While endotoxins   more toxid, extosins   toxoid
While endotoxins do not more toxid, extosins do form toxoid
66
An example of a "superantugen" is  . Superantigen grabs  and   are forces them together. It causes a   activation of T-cells. It causes the release of cytokines AKA  
An example of a "superantugen" is staphylococcal enterotoxin . Superantigen grabs MCH II and TCR are forces them together. It causes a non-specific activation of T-cells. It causes the release of cytokines AKA cytokine storm
67
Porins
• Channels in outer membrane which permit
transport of small   materials into the
 
Porins
• Channels in outer membrane which permit
transport of small hydrophilic materials into the
periplasm
68
Antibiotics (Ab) can place   pressure on
the bacteria resulting in mutation of  to
exclude drug passage
Antibiotics (Ab) can place selection pressure on
the bacteria resulting in mutation of porins to
exclude drug passage
69
Transposons (Transposable
Elements)
- Sequence of DNA encoding a 
enzyme bounded on either end by i 
Transposons (Transposable
Elements)
- Sequence of DNA encoding a transposase
enzyme bounded on either end by inverted
repeats (IR)
70
  can carry genes for antibitoic resistance
Plasmids can carry genes for antibitoic resistance
71
Pathogenicity Islands
- Multiple genes surrounded by   elements that encode for virulence
properties
Pathogenicity Islands
- Multiple genes surrounded by transposon-like elements that encode for virulence
properties
72
Some strains of E. coli and other bacteria
use   for colonization
• Here  are used to initially attach to the
 
• Upon attachment the genes are activated
Some strains of E. coli and other bacteria
use pathogenicity islands for colonization
• Here pili are used to initially attach to the
enterocytes
• Upon attachment the genes are activated
73
Type III secretion systems
o A set of proteins that form a channel
from the   to the host
cell cytoplasm – easy way to transfer
bacterial proteins into the host cell
Type III secretion systems
o A set of proteins that form a channel
from the bacterial cytoplasm to the host
cell cytoplasm – easy way to transfer
bacterial proteins into the host cell
74
Intimin-intimin receptor
o Intimin receptor is made by the bacteria
and transferred through the  system into the host cell which
is placed in the host cell membrane
o Intimin on the bacterial surface can now
bind the   on the host cell
membrane and facilitate   of the bacteria to the host
Intimin-intimin receptor
o Intimin receptor is made by the bacteria
and transferred through the type III
secretion
system into the host cell which
is placed in the host cell membrane
o Intimin on the bacterial surface can now
bind the intimin receptor on the host cell
membrane and facilitate strong
adherence
of the bacteria to the host
75
Plasmids are small circular DNA that replicates
  of the bacterial chromosome. They can integrate into  
Plasmids are small circular DNA that replicates
independent of the bacterial chromosome. They can integrate into bacterial DNA
76
Conjugative Plasmids ( -plasmids)
- Encodes   enzyme and   pili
genes
-Transferable to other  bacteria
Conjugative Plasmids (F-plasmids)
- Encodes transfer enzyme and sex pili
genes
-Transferable to other “similar” bacteria
77
Nonconjugative Plasmids
- Lack  genes
-Transferable to other bacteria if in a cell
already containing an  
Nonconjugative Plasmids
- Lack transfer enzyme genes
-Transferable to other bacteria if in a cell
already containing an F-plasmid
78
  are viruses that infect bacteria. Each “species” of phage has a  bacterial host
o Can be exploited so as to “type” or classify bacteria ( )
Bacteriophages are viruses that infect bacteria. Each “species” of phage has a specific bacterial host
o Can be exploited so as to “type” or classify bacteria (phage
typing
)
79
Bacteriophaes have DNA or RNA that is injected through a pore in the   that is  - 
Bacteriophaes have DNA or RNA that is injected through a pore in the base plate that is spring-loaded
80
  bacteriophages degrade   and when it repackages, after replicating its own DNA it may repackage some bacterial DNA. When it lyses, it can transfer some of that   and the bacteria can then incorporate it. Called  
Lytic bacteriophages degrade host genome and when it repackages, after replicating its own DNA it may repackage some bacterial DNA. When it lyses, it can transfer some of that bacterial DNA and the bacteria can then incorporate it. Called GENERALIZED TRANSDUCTION.
81
 /  bacterioophage injects its DNA it incorporates within   and then it excises out and replates. It takes some of the bacterial DNA with it and every new phage that's made now has that gene. Called  .
Lysogenic/Temperate bacterioophage injects its DNA it incorporates within bacterial chromosome and then it excises out and replates. It takes some of the bacterial DNA with it and every new phage that's made now has that gene. Called SPECIALIZED TRANSDUCTION.
82
  is when DNA released by dying bacteria is taken up by
viable bacteria and incorporated into the
genome
Transformation is when DNA released by dying bacteria is taken up by
viable bacteria and incorporated into the
genome
83
  is the ability of a bacterium to take up naked DNA
Competence is the ability of a bacterium to take up naked DNA
84
The 4 naturally competent bacteria are
1.  
2.  
3.  
4.  
The 4 naturally competent bacteria are
1. Streptococcus pneumoniae
2. Neisseria gonorrhoeae
3. Haemophilus influenzae
4. Helicobacter pylori
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