microbio 4000 osu ch 18

What are the five required steps for a pathogen to cause disease in its host (pathogenesis)

1. Entry into host, vulnerable to immune system

2. Attachment and colonization

3. Avoidance of host immunity

4. Host damage

5. Exit from host, and infect others

Virulence factors

These are traits that enhance a pathogen's ability to cause disease

• Pili (attachment, movement, sex)

• Enzymes that harm the host or prevent detection (trick or distract host)

• Proteins that disrupt normal cellular function (ex. replicate in the phagosome)

• Capsule

• Enzymes that inactivate antibiotics (beat out competitors)

Major mechanism that bacteria use to acquire new virulence factors

Horizontal gene transfer, they can even transform non-pathogens into pathogens!

Horizontal gene transfer: transformation, conjugation, transduction and transposition

• Transformation - naked/dead DNA picked up by cell

• Conjugation - sex pili used

• Transduction - bacteriophage

• Transposition - "jumping genes" copy + pasting from genomes

Genomic island

When a whole block of DNA is transferred by HGT from one organism to another, and is integrated into the host chromosome

Pathogenicity island

If the genomic island increases the fitness of a microbe in its host (virulence factors)

Identification of a pathogenicity island

Pathogenicity islands look different compared to the rest of the genome (such as having a lower GC content)

Typically flagged by phage or plasmid genes

Adhesins

Any microbial virulence factor that are required for attachment

Why is attachment required for all microbes that colonize in a host?

To avoid being removed from the organism

Which monomers make up pili adhesion molecules

Pilin protein

Which region of pili is assembled first, what does it have on it?

The tip of the pili is assembled first at the cell surface it contains the adhesin protein that binds to host receptors

Which region of a pili interacts with host receptors?

The tip, as it contains the adhesin protein that binds to host receptors

Type I pili

Static, hairlike appendages used only for

attachment (think: velcro, adhesion only)

Type IV pili

Dynamic, thin, and flexible for "twitching

motility", also energetically expensive (think: fishing rods, adhesion and motility)

Are all adhesions pili?

Nope! Different adhesins enable attachment to different tissues, and determine the host species and cell types these bacteria will attach and colonize!

Know that most bacteria colonizing the body will do so as....

Biofilms

Surfaces which biofilms can form on in the body

Organic (ex. lungs, bladder, skin, stomach lining) or inorganic (ex. catheters and surgical implants)

What is quorum sensing?

Cell-to-cell communication which enables biofilms to coordinate behavior, positive feedback loops

Why do biofilm-forming infections lead to chronic infections, which will also lead to chronic inflammation?

The presence of biofilms chronically activates Toll-Like receptors and triggers inflammation, biofilms also generally resist host defenses and antimicrobial compounds

Order of bacterial pathogenesis (extracellular bacteria)

1) entry into the body

2) adhesion to host cell surface or tissue

3) colonization

4) biofilm development

Possible order of bacterial pathogenesis (intracellular bacteria)

1) adhesion to host cell surface or tissue

2) entry into the body

3) colonization

4) biofilm development

If a pathogen gets to the colonization step, it is at risk of what?

Being sensed and removed by the immune system

How do pathogens sense they are in our body?

Pathogens use the same mechanisms to sense environmental conditions in the outside world as it does within a host (temperature, nutrients, pH)

When are virulence factors expressed?

When environmental cues pathogens to do so

How capsules help extracellular bacteria use to avoid being sensed or removed by the immune response

Coat bacterial cell walls that mask PAMPs and antigens (makes bacteria harder to detect), and prevent phagocytes from binding (prevents us from producing antibodies, and destroying the bacteria).

How protein A helps extracellular bacteria use to avoid being sensed or removed by the immune response

Sequester antibodies by binding to the Fc region of antibodies

How cell-cell communication in biofilms via quorum sensing helps extracellular bacteria use to avoid being sensed or removed by the immune response

Induce virulences factor gene expression

How manipulation of immune cells help extracellular bacteria use to avoid being sensed or removed by the immune response

Produce cytokines

How varying surface antigens help extracellular bacteria use to avoid being sensed or removed by the immune response

Avoid immune detection

How secreting fake "cytokines" help extracellular bacteria avoid being sensed or removed by the immune response

It influences the immune system

Facultative intracellular pathogens

Invade host cells but can also survive outside the host cell

(ex. Salmonella, Listeria)

More likely to spread from person to person

Obligate intracellular pathogens

Invade and reproduce inside a host cell only (ex. Rickettsia, Coxiella, Bartonella)

Will intra or extracellular bacteria be more innately hidden from host immune cells?

Intracellular bacteria, but it may still be detected or removed

Three fates of endocytosed/phagocytosed bacteria

Fate 1: can survive and replicate within phagolysosomes (hijack fate)

Fate 2: prevent lysosome fusion and persist in phagosome

• exocytosis can expel bacteria into extracellular space (french exit fate)

• phagocytes can ingest pathogens and deliver them to lymph node (lymph fate)

Fate 3: can break out of the phagosome and move throughout the cytoplasm and adjacent cells (rocket fate)

What is endotoxin? What types of bacteria express it? Why is it called an endotoxin?

Also known as lipopolysaccharide (LPS), is an important virulence factor common to all Gram-negative bacteria. It is a toxin because upon its release, it causes a cytokine storms which can lead to sepsis

Which component of LPS acts as the endotoxin?

Lipid A

In what situation is the endotoxin released?

When Gram-negative cells die, they release the lipid A component of LPS

What senses endotoxin and what is the result?

Toll-like receptors which leads to a dramatic release of proinflammatory cytokines

How do endotoxins drive sepsis?

Endotoxin activation of toll-like receptors causes a "cytokine storm," which contributes to the signs/symptoms of sepsis:

• Fever

• Activation of clotting factors

• Activation of complement

• Vasodilation → low blood pressure → shock

• Death

How do bacterial exotoxins differ from endotoxin?

Exotoxins are secreted by bacteria to alter host cell function, disrupt the immune system, or outright kill the host cell to obtain nutrients (cause direct damage to cell), endotoxins are simply a PART of gram-negative cells, that just so happen to cause damage when the cells are killed

Exotoxins are..... (how do they get to the host?)

secreted

Exotoxin Modes of Action

- Plasma Membrane Disruption

- Cytoskeleton Alterations

- Protein Synthesis Disruption

- Cell Cycle Disruption

- Signal Transduction Disruption

- Cell-Cell Adhesion Disruption

- Redirection of Vesicle Traffic

- Blockage of Exocytosis

Which membrane are exotoxins transported across in Gram-positive cells? Gram-negative cells?

talk to alina, cytoplasmic membrane?

What type of bacteria use the specialized Type II, III, and IV secretion systems?

All gram neg!

Where does the general secretion pathway transport proteins in gram pos bacteria vs gram neg

In Gram-positive cells, the general secretion pathway transports proteins outside the cell, and into the periplasm for Gram-negative cells

Type II secretion system mechanism

Acts as a piston that uses ATP to push proteins out of the cell into extracellular space

Type III secretion system mechanism

Acts as a needle that uses ATP to 'inject' proteins into host cells

Type IV secretion system mechanism

Uses modified conjugation pilus that transports toxins instead of DNA, puts toxin directly into target

The definition for viruses

Obligate, intracellular parasites! All viruses are pathogens in their host, and all pathogens are parasites

A virus outside of its host cell is completely inert: no transcription/translation, no energy, etc. How does this compare to a bacterial cell outside of its host organism?

Bacteria can survive in multiple environments, due to their ability to metabolize

Antigenic variation

Generates "stereotypes" which are the same species of virus with distinct antigens that do NOT offer cross-protection, as they each generate a unique adaptive immune response

Antigenic shift

Dramatic and sudden change in a viral genome, leading to host having NO protection against a virus, how endemics start!

Antigenic drift

Small mutations that happen occasionally, like the virus goes on vacation and gets a tan, the immune system no longer recognizes it and it is able to evade the immune system

Why is the flu virus more pathogenic than the rhinovirus

-Rhinoviruses replicate more effectively at 33C (colder than body temp), and flu at 27C

-PAMPS from flu trigger pro inflammatory cytokine production in upper and lower respiratory tract

- flu makes host more susceptible to secondary infections

HPV viral pathogenesis strategies

- antigenic variation: HPV has hundreds of stereotypes that each generate unique immune responses

- transforms host cell: HPV protein increases division of virus-infected cells

- immortality: host cells become immortal and replicate uncontrollably which can lead to cancer

What type of viral infection has a stage that does not cause disease?

Latent

What process allows latent viruses ro replicate and cause disease?

They enter nerve cells and express a latency mRNA that prevents expression of viral genes

Three ways which HIV repress the immune system

- deplete CD4 helper T cells (no helper T cells = no active immunity)

- inhibit apoptosis of virus-producing cells (prevents viral cells from dying) while initiating death of unionfected cells (killing healthy cells)

- down-regulates CD4 and MCH-I to hide from CD8 cytotoxic T lymphocytes (prevents activation of humoral immunity)