MICR223_L13_Intracellular survival

What are the main learning objectives for MICR223?

Describe mechanisms that phagocytes use to kill microbes and understand strategies of bacteria like Salmonella, Legionella, and Listeria to avoid phagocytic antimicrobial activities.

What type of cells are considered phagocytes?

Macrophages and neutrophils.

How do some microbes avoid being killed by phagocytes?

They use evolved strategies to evade antimicrobial activities, survive, and replicate in human cells.

What is the role of phagosomal pH in antimicrobial activity?

It activates proteases and hydrolases and most bacteria cannot deal with low pH.

What are reactive oxygen species (ROS)?

Highly reactive molecules like superoxide and hydroxyl radicals that damage bacterial macromolecules.

What is the function of cationic antimicrobial peptides (CAMPS)?

They have a hydrophobic face that disrupts bacterial membranes, leading to bacterial lysis.

What phenomenon allows Salmonella to survive in an acidic compartment?

Salmonella uses effector proteins injected through a type III secretion system to evade killing.

What is the outcome of Salmonella infection in a human cell?

It can replicate extensively in a remodeled lysosomal compartment.

What is the role of superoxide dismutase (SOD) produced by Salmonella?

It detoxifies superoxide, preventing the formation of hydroxyl radicals.

How do the PhoP/PhoQ and PmrA/PmrB systems help Salmonella?

They modify lipopolysaccharide (LPS) to prevent binding of cationic antimicrobial peptides.

What is Legionella pneumophila known for?

It causes Legionnaires’ disease, primarily affecting immunocompromised individuals.

Why does Legionella pneumophila avoid fusion with lysosomes?

It alters host trafficking pathways to prevent its destruction.

What protects Legionella from phagocytic killing?

Formation of Legionella-containing vacuoles (LCVs) derived from the ER.

What is the significance of the Dot/Icm type IV secretion system in Legionella?

It mediates the acquisition of ER-derived membrane and prevents maturation into lysosomes.

Which protein in Legionella is important for evading host defenses?

The Dot/Icm type IV secretion system, which uses 25 substrate proteins.

What disease does Listeria monocytogenes commonly cause?

Meningitis, especially in immunocompromised or pregnant individuals.

What is listeriolysin O (LLO)?

A cholesterol-dependent pore-forming toxin in Listeria that lyses phagosomes.

Which enzymes allow Listeria to escape the phagosome?

PlcA and PlcB, which hydrolyze phospholipids in the phagosomal membrane.

How does Listeria utilize host cells for energy?

It takes glucose 1-phosphate from host cells for its glycolytic pathway.

What motility mechanism does Listeria use to spread between cells?

It uses actin polymerization driven by the surface protein ActA.

What role does ActA play in Listeria's intracellular motility?

It interacts with host actin to promote the addition of actin monomers, pushing the bacterium forward.

What type of bacteria is Listeria monocytogenes classified as?

A Gram-positive, food-borne pathogen.

How does Listeria evade the immune response?

By spreading efficiently inside host cells and subverting actin to avoid detection.

Why does Legionella use a type IV secretion system?

To deliver effector proteins into host cells, helping it replicate and evade killing.

What type of pathogen is Salmonella categorized as?

A facultative intracellular pathogen that can survive inside human cells.

How do macrophages typically deal with ingested bacteria?

They internalize bacteria into a phagosome that acidifies and fuses with lysosomes.

What happens to bacterial macromolecules in the presence of reactive oxygen species?

They get oxidized, leading to damage of proteins, lipids, and DNA.

What are the consequences of Listeria's double-membrane vacuole lysis?

It allows the bacteria to escape to the cytosol and repeat the infection cycle.

What is the primary goal of Salmonella's virulence factors?

To ensure its survival and replication inside host cells despite immune responses.

How does the low pH affect the activity of phagosomal enzymes?

It activates enzymes like cathepsins that can damage bacteria.

What is one of the main defenses against reactive oxygen species that Salmonella employs?

The production of catalase to detoxify hydrogen peroxide.

Why is the regulation of LLO activity crucial for Listeria?

To ensure LLO primarily acts in the phagosome and does not damage the host cell.