intracellular bacteria Flashcards
[1] Explain the advantages and disadvantages of an intracellular lifestyle inside phagocytic and non-phagocytic host cells.
Nutritional: intracellular pathogens avoid competition for space and nutrients with other microbes. Protection from immune system. Protected disseminatin around the body. Disadvantages: host defenses
Facultative vs obligate intracelllular pathogens
facultative: capable of both intra and extracellular growth. Obligate: cannot reproduce outside of the intracellular environment due to loss of essential biosynthetic metabolic pathways
List the obligate vs facultative intracellular pathogens
obligate: chlamydia spp, Coxiella burnetti, Ehrlichia spp., Mycobacterium leprae, Rickettsia spp. Facultative: Bartonella spp., Brucella spp., Francisella tularensis, Legionella pneumophila, Listeria monocytogenes, Mycobacterium spp., Nocardia spp., Salmonella enterica, Shigella spp.
Describe the mechanisms of bacteria entry into cells
- Zipper model: tight interaction between the bacterial cell surface ligands and the host cell receptors results in a closure of the host cell surface around the bacterium. 2. Trigger model: bacterial products induce the cell surface to ruffle,
projecting membrane extensions that surround the bacteria. (macropinocytosis)1. Zipper model: tight interaction between the bacterial cell surface ligands and the host cell receptors results in a closure of the host cell surface around the bacterium. 2. Trigger model: bacterial products induce the cell surface to ruffle,
projecting membrane extensions that surround the bacteria. (macropinocytosis)
examples of the zipper model
parasite induced phagocytosis by non-professional phagocytes (Listeria and human epithelial cells), receptor mediated phagocytosis by macrophages (mycobacterium tubercolosis and macrophages), and coiling phagocytosis (legionella pneumophilia into macrophages)
describe maturation of phagosome
Normally- internalization of inert particles > membrane bound phagosome recycles membrane proteins > form a phagolysosome > kills microbes, degrades molecules and presents antigens
list antimicrobial defenses of professional phagocytes
- NADPH oxidase-reduction of oxygen to superoxide gives rise to reactive oxygen species. 2. Inducible nitric oxide synthase- NO synthases produce NO which targets many intracellular pathogens. 3. Oxygen-independent effector molecules- antibacterial peptides throughout the cytosol with broad spectrum antimicrobial activity. Decreased expression of transferrin and increased expression of iron storage proteins reduces the iron available to intracellular pathogens to levels that are non compatible with life. Also low pH in phagolysosomes
Describe strategies used by intracellular pathogens to avoid NADPH oxidases
Listeria escapes from the phagosomal vacuole to the cytosol where the NADPH oxidase cannot be assembled; Legionella pneumophila inhibits the
mobilization of cytosolic components of the NADPH oxidase to the membrane; the agent of
human granulocytic ehrlichiosis selectively inhibits transcription of one of the subunits of the
phagocyte oxidase. Salmonella uses superoxide dismutase and catalase for the detoxification of
reactive oxygen species.Listeria escapes from the phagosomal vacuole to the cytosol where the NADPH oxidase cannot be assembled; Legionella pneumophila inhibits the
mobilization of cytosolic components of the NADPH oxidase to the membrane; the agent of
human granulocytic ehrlichiosis selectively inhibits transcription of one of the subunits of the
phagocyte oxidase. Salmonella uses superoxide dismutase and catalase for the detoxification of
reactive oxygen species.
How does listeria adapt to intracellular life
Listeria lyses the phagocytic vacuole, escaping into the cytosol. In the cytosol, Listeria polymerizes actin at one its poles,an event that propels the bacteria within the cytosol. These actin tails also allow bacteria to invade neighboring cells without ever being exposed to the extracellular environment
Listeria- advantages and disadvantages
Advantage: By escaping into the cytosol, they have access to large amounts of nutrients, and minimize their exposure to antimicrobial defenses associated with vesicles. disadvantages: Cytosolic antimicrobial peptides and inducible nitric oxide synthase can target them. In addition, cytotoxic CD8 positive T cells can lyse infected cells expressing on their surface MHC class I molecules in association with microbial peptides.Advantage: By escaping into the cytosol, they have access to large amounts of nutrients, and minimize their exposure to antimicrobial defenses associated with vesicles. disadvantages: Cytosolic antimicrobial peptides and inducible nitric oxide synthase can target them. In addition, cytotoxic CD8 positive T cells can lyse infected cells expressing on their surface MHC class I molecules in association with microbial peptides.
What are non fusogenic organisms
Intracellular pathogens contained in membrane-bound compartments that avoid the degradation pathway ultimately linked to lysosomal fusion
Non-fusogenic organisms advantages
Ensures bacteria remain viable inside phagosome and avoids activation of immune system via presentation of peptides on class II MHC.
Non-fusogenic organisms disadvantages
These organisms tend to cause long term infection by formation of granulomas which contain macrophages and T cells. The granuloma contains the infection by maintaining a balance btw organism growth and antimicrobial host defenses
List the non-fusogenic organisms and their mechanisms
Mycobacterium: stay in early endosomal compartments that hardly acidify. Legionella: reside in autophagic vacuole (ER). Chlamydia: intercepts trafficking from golgi.
What are fusogenic organsisms
Coxiella burnetii is the only intracellular pathogen to reside within a phagolysosome. The organism is not cytopathic reaching very high numbers in a single vacuole.
