Fun with Flagellated Friends: Fun with Flagellated Friends Leishmania – Life cycle and social impact Vector – The Female Sandfly: Vector – The Female Sandfly Reservoir Hosts: Reservoir Hosts Foxes, Jackals, Rodents, Wolves, Chickens, Horses
And most importantly--
DOGS Two Life-cycle stages: Two Life-cycle stages
-elongated, with flagella (10-20 µm long)
-occur extracellularly in the insect midgut
-round (3-7 µm diameter)
-occurs intracellularly, during mammalian stage
-nonmotile The Blood Meal (fly becomes vector): The Blood Meal (fly becomes vector) Female sandfly bites a host (usually a nonhuman animal), intakes amastigotes through proboscis.
Amastigotes reproduce via binary fission and transform in the sandfly’s midgut into promastigotes.
How do promastigotes get from the gut back to the proboscis? Development Inside the Sandfly: Development Inside the Sandfly Repeated division blocks the fly gut, resulting in travel forward into the pharynx and blockage of the sucking apparatus
Chitinolytic enzymes damage the fly cardiac valve, allowing for reverse flow into proboscis Human Infection (AKA where did I put my insect repellent?): Human Infection (AKA where did I put my insect repellent?) Macrophage Lysis: Macrophage Lysis Macrophage defenses: Macrophage defenses Oxidative burst
peroxide (H2O2), superoxide anion (O2-)
Enzyme Digestion Intracellular Survival: Intracellular Survival Leishmania defense mechanisms: Leishmania defense mechanisms Produces enzymes to neutralize the oxidative burst of the macrophage.
Proton pump to keep the intracellular pH close to neutral.
Surface glycoproteins that degrade lysosomal enzymes. Inactivation of oxidative burst products via enzyme action: Inactivation of oxidative burst products via enzyme action
O2- + O2- + 2H+ O2 + H2O2
Catalase or trypanothione peroxidase
H2O2 + H2O2 O2 + 2H2O
Surface glycoproteins: Surface glycoproteins LPG – inhibits oxidative burst; mediates attachment of promastigotes to gut wall.
gp63 – degrades lysosomal enzymes Cutaneous Leishmaniasis: Cutaneous Leishmaniasis Mucocutaneous Leishmaniasis: Mucocutaneous Leishmaniasis Visceral Leishmaniasis: Visceral Leishmaniasis Global Status: Global Status