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What are the main components of a typical prokaryotic cell envelope?
Cytoplasm, plasma membrane, cell wall (peptidoglycan), and outer membrane (in Gram-negative bacteria with LPS).
What is the role of LPS in Gram
negative bacteria?- LPS forms the outermost layer, providing protection and acting as a potent immune stimulator (endotoxin).
What are the three structural regions of LPS?
Lipid A (toxic anchor), core oligosaccharide (stabilizing connector), and O-antigen (variable polysaccharide defining serotypes).
Why is LPS biologically important?
It protects bacteria from stress and antibiotics, triggers immune responses, contributes to pathogenesis, and serves as a vaccine/antibiotic target.
What is Lipid A and why is it called endotoxin?
Lipid A anchors LPS and triggers fever, inflammation, and septic shock when released during infection.
What is the Raetz pathway?
The nine-enzyme pathway (LpxA → LpxC → LpxD → LpxH → LpxB → LpxK → KdtA → LpxL → LpxM) that synthesizes Kdo₂-Lipid A.
What is Kdo₂
Lipid A?- The minimal essential LPS structure critical for outer membrane integrity.
How is LPS transported across membranes?
Synthesized in the inner membrane, flipped by MsbA, and exported via the LptABCDEFG complex (PEZ dispenser model).
What happens if LPS biogenesis is disrupted?
Causes membrane instability, antibiotic susceptibility, or cell death.
How does LPS trigger immune responses?
Lipid A binds TLR4/MD-2 receptors on macrophages, activating NF-κB and cytokine release.
What is sepsis and how is it linked to LPS?
A severe inflammatory response to infection; high LPS levels trigger cytokine storms leading to shock and organ failure.
What are smooth vs rough colonies?
Smooth have full O-antigen (more virulent); rough lack O-antigen (less virulent).
How is O
antigen regulated?- The Wzz system controls O-antigen chain length (S-, L-, VL- forms).
What antibiotic targets LPS transport?
A new class (Pahil et al., Nature 2024) traps LPS in the Lpt transporter, blocking membrane assembly.
How do macrophages recognize LPS?
Through TLR4/MD-2, which activates cytokine production leading to inflammation or sepsis.
What are key innate immune responses to LPS?
Phagocytosis, cytokine release, and antigen presentation to activate adaptive immunity.
What are the main takeaways about LPS?
LPS is immunogenic, Lipid A is toxic, structure variation aids immune evasion, and LPS pathways are antibiotic targets.