Module 12 - Bacterial Pathogenesis Flashcards
In what two groups can bacteria be divided into?
Pathogenic and nonpathogenic
What is pathogenesis?
Processes used by pathogens to produce disease
What are the key aspects of bacterial pathogenesis?
Attachment to host tissue to gain access, avoid host defense, damage host tissues to get nutrients and replicate
What is a principle feature in pathogen evolution?
Genetic mobility
What are virulence factors?
Pathogen products that enhance the ability to cause disease
In what common ways do virulence factors act?
They can gain access to tissue, overcome host defense, and get nutrients (by damaging cells or stealing from the host)
What diseases does Neisseria gonorrhoeae lead to?
STIs such as gonorrhea
What virulence factors are produced by Neisseria gonorrhoeae?
Fimbriae, IgA protease, and LOS
What does Neisseria gonorrhoeae do with its fimbriae?
Attaches to host cell and invades underlying tissues
What does Neisseria gonorrhoeae do with LOS?
It invokes an intense inflammatory response in the host
Why would a pathogenic bacteria want to induce inflammation?
It damages host tissue, which facilitates invasion and provides nutrients
How come pathogenic bacteria want to stop the host immune system?
The host defense system can stop entry and growth of pathogenic bacteria
What does Neisseria gonorrhoeae do with IgA protease?
It uses it to avoid the host defense system
How can pathogenic bacteria avoid the host defense system?
By changing surface antigens, or by producing IgA protease
What disease does Bordetella pertussis lead to?
Whooping cough
What disease does Escherichia coli O157:H7 lead to?
Hemorrhagic colitis and kidney failure
What disease does Helicobacter pylori lead to?
Gastritis, ulcers
What disease does Streptococcus pneumoniae lead to?
Pneumonia, meningitis
What disease does Streptococcus pyogenes lead to?
Various skin, throat, and systemic infections
What do the symptoms of Neisseria gonorrhoeae depend on?
The site of infection
What do nonpathogenic bacteria do (when growing)?
They colonizes and do not directly attach to host cell
What are some common attachment factors used by pathogenic bacteria?
Fibronectin binding proteins, fimbriae, outer membrane molecules, and other specialized proteins for attachment
What are adhesions?
Molecules that allow bacteria to bind to host tissues
In which bacteria are fibronectin binding proteins best studied in?
Streptococcus pyogenes, Staphylococcus aureus, and E. coli
What is fibronectin?
A plasma glycoprotein in plasma and as fibers in extracellular matrix
How come fibronectin is a prime target for pathogen binding?
It is present everywhere
What disease does Corynebacterium diphtheria lead to?
Diptheria
What disease does Clostridium difficile lead to?
Colitis
What disease does Clostridium perfringens lead to?
Gas gangrene
What disease does Mycobacterium tuberculosis lead to?
Tuberculosis
What disease does Staphylococcus aureus lead to?
Various skin and invasive diseases
What disease does Streptococcus pyogenes lead to?
Various invasive and toxic diseases
What disease does Treponema pallidum lead to?
Syphilis
What disease does Borrelia burgdorferi lead to?
Lyme disease
What disease does Porphyromonas gingivalis lead to?
Gum disease
What do fimbriae do?
They are used for attachment to host tissues and nonbiological surfaces (medical implants)
What is a fimbriae?
A specialized pili with an adhesive tip?
How come fimbriae are used to aid in adhesion?
It can help span the distance of repulsion
What repulsion is there when bacteria try to bind to host tissues?
Cell surfaces have net negative charge that causes electrostatic repulsion
What is found at the end of a fimbriae strand?
A specific adhesive tip composed of a tip protein
What does the adhesive tip of a fimbriae do?
It is used for attachment by targeting oligosaccharides
True or false: several different types of fimbriae can be produced by a single bacterium
True: they are frequently modified
Why are fimbriae modified?
To respond to environmental conditions
How does Neisseria gonorrhaea use its fimbriae?
It is needed for attachment to epithelial cells of urethra and cervix
What happens once infection has been established (in terms of fimbriae)?
Fimbriae expression can be turned on or off
How can fimbriae avoid host immune system?
By undergoing an amino acid change through genetic combination
What is the consequence of fimbriae undergoing amino acid change?
By the time one specific antibody is made, another fimbriae is produced
How do E. coli cells form lesions to obtain nurtients?
Through interactions of intimate virulence factors
What special adherence proteins are used by E. coli?
Intimin and Tir
Where is Tir found?
It is produced by E. coli, and translocated to intestinal cells
Where is Intimin found?
It is produced by E. coli
When do intestinal cells express Tir?
When E. coli insert it through a type III secretion pathway
What happens once Tir is inserted into intestinal cells?
It can interact with Intimin found on the E. coli cell
What happens when Tir interacts with Intimim?
A pedestal is formed for the E. coli cell
What is a capsule?
A well organized polysaccharide layer that surrounds some bacterial cells
What is another name for a capsule?
The glycocalyx
What are capsules composed of?
Usually polysaccharides, but sometimes polypeptides
True or false: capsules can help adhere to surfaces
True: they can bind to receptors to help adhere to surfaces
What is the primary role of capsules for pathogens?
To protect the bacterium from early immune defenses (phagocytosis and lyse from complement)
What happens to nonencapsulated bacteria (in terms of early immune defenses)?
They are opsonized and are regularly phagocytosed by phagocytes
What happens to encapsulated bacteria (in terms of early immune defenses)?
The antibody must move through the capsule to attach to the cell surface, so it will not be available for phagocyte binding
What is needed for phagocytosis of encapsulated bacteria to occur?
An antibody specific to the capsule
What is the result of constructing a capsule from host self molecules?
It prevents stimulation of the host immune response
What is the purpose of capsules containing water?
It protects the bacteria against desiccation
What do capsules exclude?
Bacterial viruses
True or false: immunity to one type of capsule is sufficient
False: immunity to one capsule type does not result in immunity to other types
What is the capsule of Bacillus anthracis made out of?
Poly-D-glutamic acid
What is the capsule of Streptococcus pyogenes made out of?
Hyaluronic acid
What is the capsule of Haemophilus influenzae made out of?
There are six different capsule types
What is the capsule of Neisseria meningitidis made out of?
Sialic acid
What is the capsule of Pseudomonas aeruginosa made out of?
Alginate (biofilm formation)
How do bacteria release toxins or virulence factors?
Either through their lysis, secretion to extracellular environment, or injection directly into a host cell
What are major virulence factors in gram negative bacteria?
Type III and Type IV secretion systems
What are some examples of gram negative bacteria that use Type III secretion systems?
E. coli, Shigella sonnei, Klebsiella pneumoniae, Nesseria gonorrhoeae, Salmonella Typhimurium
What are Type III secretion systems?
Injection assemblies that deliver virulence factors directly into the target cell
How do Type III secretion systems work?
They form a channel that passes through plasma membrane and outer membrane of pathogen and host cell membrane
Which is more common: Type III or Type IV secretion systems?
Type III secretion systems
How do Type IV secretion systems work?
They deliver molecules across the plasma membrane to inject virulence factors
What are Type III and IV secretion systems often encoded with?
The gene products that they will inject
Why is iron a limiting nutrient for the pathogen?
It is kept tightly bound by host iron binding proteins
What are the 4 strategies pathogens can use to obtain iron from the host?
Siderophores, transport proteins, low pH, and hemolysin
What are siderophores?
Bacterial iron binding proteins
How do siderophores obtain iron?
They compete with host iron binding proteins for iron
How are transport proteins used to obtain iron?
They can transport host iron binding proteins into the bacterial cell
How can low pH be used to obtain iron?
It reduces the ability of host iron binding proteins to bind to iron
What do hemolysins do?
Lyse red blood cells
How can hemolysins be used to obtain iron?
They can lyse red blood cells to release intracellular iron and other nutrients
Why do bacteria use toxins?
To gain nutrients from the host
What is a toxin?
A poisonous substance produced by an organism
What are the two categories of toxins?
Endotoxins and exotoxins
What are endotoxins, and what do they do?
They are part of the cell wall structure, and induce inflammatory responses
What are some examples of endotoxins?
LPS and LTA
What type of bacteria use LPS?
Gram-negative bacteria
What type of bacteria use LTA?
Gram-positive bacteria
What does LPS stand for?
Lipopolysaccharide
What does LTA stand for?
Lipoteichoic acid
What are exotoxins?
Soluble proteins released outside of the producing cell, or passively released upon bacterial lysis
What are some examples of exotoxins?
AB toxins, cytolysins, and super antigens
What are AB toxins?
Exotoxins with two subunits (A and B)
What does the A subunit do in an AB toxin?
It has toxic enzymatic activity
What does the B subunit do in an AB toxin?
It binds to the host cell receptor
Generally, what is a cytotoxin?
A substance toxic to cells
What are cytolysins?
Bacterial cytotoxins that act on the plasma membrane
What are super antigens and what do they do?
Exotoxins that can non specifically stimulate T cells to secrete cytokines
What does LOS stand for?
Lipooligosaccharide
What is the structure of LOS?
Lipid A and a core polysaccharide
What is the structure of LPS?
Lipid A, a core polysaccharide, and an O antigen
How was LPS discovered?
Scientists isolated a heat stable element from gram negative bacteria that was responsible for many toxic effects of systemic diseases
Where is LPS found?
In the outer membrane of gram-negative bacteria
What is the most common type of endotoxin?
LPS
What is the composition of the O antigen?
Repeating units of polysaccharide
What does the O antigen do?
It is strain specific, and the target of the immune response
What is used for serotyping?
The O antigen
What is the composition of the core polysaccharide?
Various sugars with side chains that are genus or species specific
What is the innermost component of LPS?
Lipid A
What does Lipid A do?
It anchors LPS to outer membrane, and causes inflammation
What is the composition of Lipid A?
Unusual fatty acids
What is the toxic portion of LPS?
Lipid A
What does Neisseria meningitis cause?
Inflammation of meninges
What are meninges?
Lining that surrounds the brain and spinal cord
What was shown to be responsible for the toxic properties of Neisseria meningitis?
Lipid A
What does endotoxin do in low concentration?
It stimulates immune system response that can prevent disease
True or false: systemic production of endotoxin is deadly
True: this can overwork the immune system
Where is LTA found?
Anchored to the plasma membrane in most gram positive pathogens
What is LTA?
A cell wall molecule
True or false: LTA is recognized by TLRs?
True: like LPA, LTA is recognized by TLRs
What does LTA do?
It induces inflammation
True or false: LTA is useful in small quantities
True: the endotoxin produces septic shock only when there are large amounts of bacteria present
What is the protective activity of a fever?
Inhibition of pathogen replication, increase in immune cell activities
What is the protective activity of complement activation?
Lysis by MAC formation, induction of inflammation
What is the protective activity of inflammation?
Transport of immune cells and molecules to site of infection
What is the protective activity of B-cell proliferation?
Antibody production
What is the protective activity of IFN-gamma expression from T cells
Activation of macrophages and NK cells
What is the protective activity of stimulation of the clotting cascade?
Prevention of pathogen spread
How are exotoxins grouped?
By structure (AB toxins), molecular activity (super antigens), or cellular activity (cytotoxins)
Which bacteria have an AB toxin with one B subunit?
Diptheria, tetanus, and botulinum
Which bacteria have an AB toxin with multiple of the same B subunit?
Cholera and Shiga
Which bacteria have an AB toxin with multiple different B subunits?
Pertussis
How does Corynebacterium diphtheria AB toxin spread?
It is absorbed in the circulatory system, where it is distributed to other organs (heart, kidney, liver, and spleen)
What does Corynebacterium diphtheria AB toxin do?
It prevents protein synthesis
How does Corynebacterium diphtheria AB toxin enter the host cell?
Through receptor mediated endocytosis
What happens when the AB toxin is in the endosome?
Acidification causes a conformational change, forming a channel
What happens once the B subunit forms a channel in the endosome?
The A subunit can inactivate EF2 to stop protein synthesis
What does EF2 do?
It is a translation factor needed for protein synthesis
What does EF2 stand for?
Elongation factor 2
Which bacteria produces Shiga toxin?
E. coli O157:H7
How come cattle, pigs, sheep, and deer can be a reservoir of infection for Shiga toxin?
These animals do not have the Shiga receptors, but these receptors are enriched in human kidney cells
What do Shiga toxins do?
They cleave ribosomal RNA to prevent protein synthesis
How does Diphtheria toxin inactivate EF2?
By adding an ADP ribose to EF2
What is ADP-ribosylation?
The process of adding an ADP ribose to a protein
How does EF2 work?
It is needed for movement of ribosomes along mRNA in eukaryotes
How does Pertussis toxin work?
It adds an ADP ribose to Gi to activate adenylyl cyclase
How does Cholera toxin work?
It adds an ADP ribose to Gs to activate adenylyl cyclase
What is the effect of increased activation of adenylyl cyclase?
Disruption of ion and water balance
What are two examples of AB toxins that cleave host proteins?
Botulinum toxin and tetanus toxin
What do botulinum toxin and tetanus toxin have in common?
They are both neural toxins, similar in structure and function, and act on SNARE proteins
What does SNARE protein stand for?
Snap receptor
What do SNARE proteins do?
They are required to release neurotransmitters
What are SNARE proteins?
A large protein super family, consisting of more than 60 members in yeast and mammalian cells
What happens when neurotoxins cleave SNARE proteins?
They prevent neurotransmitter release
What does acetylcholine do?
Causes muscle contraction
What does botulinum toxin lead to?
Flaccid paralysis (botulism)
What is flaccid paralysis?
Weakness of muscle and loss of muscle tone (limp and cannot contract)
How does botulinum toxin lead to flaccid paralysis?
It prevents release of acetylcholine
How can flaccid paralysis be fatal?
If it affects respiratory muscles (suffocation)
What is one possible cause of sudden infant death syndrome?
Infant botulism
What does tetanus toxin lead to?
Spastic paralysis (tetanus)
What is spastic paralysis?
Unusual tightness or stiffness of muscles (persistent contraction)
How does tetanus toxin lead to spastic paralysis?
It prevents release of glycine and GABA, which leads to continuous secretion of acetylcholine
What does GABA stand for?
Gamma aminobutyric acid
How do patients usually die in botulism or tetanus?
Respiratory failure
What is needed to release neurotransmitters in vesicles?
The vesicles must fuse with the neuronal plasma membrane
Which SNARE proteins help with membrane fusion?
Synaptobrevin, SNAP-25, and syntaxin
Where is synaptobrevin found?
Inserted in the vesicle membrane
Where is syntaxin found?
Inserted in the neuronal membrane
What does SNAP-25 do?
It binds to synaptobrevin and syntaxin to form a complex that allows the membranes to fuse
What is the primary role of SNARE proteins?
To mediate fusion of vesicle with target membrane bound compartments
What is needed for normal muscular contraction?
Release of acetylcholine neurotransmitter from vesicles in the terminals of motor neurons
What does botulinum toxin type A do?
It cleaves SNAP-25 to prevent muscular contraction
How toxic is botulinum toxin?
300,000x more toxic than snake venom
What is one of the most important toxins discovered?
Botulinum toxin
What toxins attack synaptobrevin?
Tetanus toxin, botulinum toxin type B, D, F, G
What toxins attack SNAP-25?
Botulinum toxin type A, C, E
What toxins attack syntaxin?
Botulinum toxin type C
How is muscular contraction halted?
By the release of neuroinhibitory neurotransmitters glycine and GABA
How does tetanus toxin move through the body?
It is taken up by motor neurons, transported to the central nervous system, and then to the inhibitory neurons
What does tetanus toxin do?
It cleaves synaptobrevin in inhibitory neurons
How do glycine and GABA work?
They act on motor neurons to block acetylcholine release, ending contraction
How does tetanus toxin lead to continuous muscle contraction?
It allows acetylcholine to be continually released from stimulated neurons
True or false: cytolysins can destruct membranes without creating lysis
True: they do not have to cause lysis
What does MDT stand for?
Membrane damaging toxin
How much of bacterial protein toxins are cytolysins?
1/3
How many cytolysins have been studied and published?
70
How are cytolysins named?
According to the cells that they can destroy
What do hemolysins do?
Lyse red blood cells
What is the result of hemolysis?
A zone of clearing surrounding the bacteria
What are hemolysis patterns used for?
Identifying streptococcus species (characteristic patterns)
What are the three different types of hemolysis?
Alpha, beta, and gamma
What is alpha hemolysis?
Partial hemolysis
What is beta hemolysis?
Complete hemolysis
What is gamma hemolysis?
No hemolysis
What type of hemolysis do streppygenes bacteria that cause strep throat cause?
Beta hemolysis
What type of hemolysis do strep pneumonia bacteria cause?
Alpha hemolysis
What type of hemolysis do Entercoccus faecalis cause?
Gamma hemolysis
What causes the green color in alpha hemolysis?
Partially decomposed hemoglobin
What categories can cytolysins be grouped into?
Pore-forming toxins and membrane degrading toxins
How do pore forming cytolysins work?
They are produced as monomers that polymerize in the membrane to form a circular pore
What is an example of a pore forming cytolysin?
Alpha toxin from Staphylococcus aureus, and perfringolysin from Clostridium perfringens
What do pore forming cytolysins do at high concentrations?
They form many holes, causing cell lysis
What do pore forming cytolysins do at low concentrations?
They allow influx of calcium ions, which causes membrane damage and induces apoptosis
How does perfringolysin work?
It binds to membrane cholesterol and contributes to tissue destruction in gas gangrene
What are the characteristics of gas gangrene?
Muscle necrosis and intense gas productions
