Lecture 3: Host-Pathogen Interactions

Identify the long and short perturbances from the bacilli

• Long = Fimbriae/Flagella

• Short = Pili

What is a “Facultative” intracellular pathogen

A bacteria that can exist intracellular/extracellular

T/F: Extracellular pathogens normally don’t invade cells but can occasionally

False, they don’t invade cells, they simply proliferate in the extracellular environment

T/F: Obligate intracellular pathogens cannot survive outside of their host cell, however, they can be grown on artificial media

False, they cannot be grown on artificial media, everything else is true

What is the difference between bacteremia and septicemia?

• Bacteremia

  • Is the presence of bacteria in the blood

• Septicemia

  • The presence and multiplication of bacteria in the blood

What is the difference between sepsis and septic shock?

• Sepsis

  • A life threatening organ dysfunction caused by dysregulated host response to infection

  • SIRS (System inflammatory response syndrome)

• Septic Shock

  • A severe complication of sepsis that can include low BP and multi-organ-failure

What is the difference between a primary pathogen and an obligate pathogen?

• A primary pathogen can cause disease in healthy hosts and is more virulent than opportunistic pathogens

• Obligate pathogens can cause disease, but the main difference is that they cannot survive outside the host for long

What are Koch’s Postulates?

1. The microorganism must be found in abundance in all organisms suffering from the disease

2. The microorganism must be isolated from a diseased organism and grown in a culture

3. The cultured microorganism should cause disease when introduced into a healthy organism

4. The microorganism must be able to be re-isolated from the newly infected organism

Are Koch’s Postulates 100% accurate every time? Why or why not

• Nope, there will always be exceptions

  • Sometimes you cannot prove a causal relationship between a microbe and disease

What are the 3 factors that affect bacterial pathogenicity?

1. Characteristics of the bacterial pathogen

   1. Genotype, virulence, tropism

2. Characteristics of the potential host

   1. Species, breed, age, sex, etc.

3. Predisposing factors

   1. Stress, nutrition, etc.

What are the 3 cells responsible for CMI?

1. T-cells

2. Macrophages

3. NK cells

What are PAMPs?

• Pathogen Associated Molecular Patterns

  • They are specific things on bacteria that uniquely identify it as a threat

What are PRRs? Which cells are they found on?

• Pathogen Recognition Receptors

  • They detect PAMPS

  • They are usually Toll-Like Receptors (TLRs)

• PRRs are found on macrophages and dendritic cells

How do macrophages destroy bacteria?

They attach to them, engulf them, phagocytize via enzymes and then release the digested products out of the cell

What is the main way that bacterial pathogens can evade the host immune system?

By disrupting TLR signaling

How do bacteria avoid intracellular destruction?

1. Prevent the lysozyme/phagosome from fusing

2. Escape into the cytoplasm of the cell

3. Gain resistance to lysozyme enzymes

Genes that control the expression of virulence in bacteria are called ______ ____

Virulence Genes

Virulence genes are tightly regulated and are ______ ____ in regards to environmental signals, ensuring their expression occurs at the appropriate stage of infection

• Switched On/Off

  • Ex: Vibrio cholerae expresses its toxin genes only when inside the host intestine

What us Quorum sensing?

A process of cell-to-cell communication that allows bacteria to share information about cells so that they can adjust their gene expression accordingly

What are the 4 main ways that bacteria can cause disease?

• By destroying tissues

• Producing toxins

• Stimulating overwhelming immune response

• Combination of the 3 above

Bacteria have virulence factors both intra/extracellularly, what are some of the main ones from both?

• Bacterial Intracellular Virulence Factors

  • Fimbriae/Pili, capsule, adhesions, LPS (Gram -)

• Bacterial Extracellular Virulence Factors

  • Toxins, enzymes, iron binding proteins

How do bacteria enter epithelial surfaces?

• Invading bacteria reach the epithelial surface

• The bacteria produce hyaluronidase and collagenase

  • Hyaluronidase

    • Breaks down/separates epithelial cells creating a gap (separates tight junctions)

  • Collagenase

    • Breaks down collagen

• The bacterial then can invade deeper tissues

Once inside the organism, how do bacteria enter the vasculature?

1. Bacteria produce coagulase

2. Clot forms around the bacteria

3. Bacteria release kinase to break down the clot and then enter the vasculature

Bacterial toxins are some of the ____ powerful poisons in nature

Most

What are the 2 types of bacterial toxins? Describe each

• Exotoxins (protein toxins)

  • Released from the cell

• Cell-associated toxins

  • LPS

  • Lipoteichoic acids

  • Peptidoglycan

What is the difference between endotoxins and exotoxins?

Endotoxins are released from within the bacteria when it dies, Exotoxins are released from the bacteria while it is alive

Why is Sepsis such a huge issue?

It can cause a Sepsis Cascade (aka cytokine storm) which can result in the widespread inflammation/damage across the body (DIC, respiratory failure, etc.)

T/F: Gram - bacteria can cause a nasty sepsis/septic shock

True

What are bacterial Super-antigens?

Potent protein toxins, often produced by bacteria like Staphylococcus aureus and Streptococcus pyogenes, that cause massive, non-specific activation of T cells

What is horizontal gene transfer? What type of genes are transferred?

• It is the transfer of genetic material between two bacterial cells (not via replication)

• Plasmids and jumping genes

What are the 3 methods of horizontal gene transfer?

1. Conjugation

   1. Two bacteria connect (F+/F-)

   2. The F+ shares some of it’s plasmid DNA with the F- cell

2. Transduction

   1. A bacteriophage (a bacterial virus) accidentally transfers bacterial DNA from one bacterium (the donor) to another (the recipient)

3. Transformation

   1. Bacteria taking up free/naked plasmid DNA from the environment (from other dead bacteria)

What are jumping genes? What carries them?

• They are self-mobilizing genes that can perform transposition in the genome

• Carried by Transposons and Integrons

T/F: Dual intracellular/extracellular pathogens use multiple virulence mechanisms to survive and grow inside/outside of the host cell

True

T/F: Attachment to and the colonization of host surface are key steps in bacterial infection

True

T/F: Host immune cells PPRs recognize bacterial PAMPs

True

T/F: Gram + cell LPS can cause endotoxemia with a massive cytokine release resulting in sepsis and septic shock

False, this describes Gram -

T/F: Bacteria are not able to share genes with different bacterial species

False

T/F: Plasmids, integrons, and transposons are mobile genetic elements

True

Horizontal gene transfer allows bacteria to evolve and adapt rapidly

True!