Lecture 4 Flashcards
Leptospira morphology
- Gram negative, obligate aerobe spirochete
- Helicoidal protoplasmic cylinder
- Motile
- Transverse division
- Oxidase, catalase, and peroxidase positive
- pH is 7.2-7.4
Size of Leptospira
- Size is 6-20um in length and 0.1um width
- Coils are 0.2-0.3um diameter and 0.5um pitch
Ultrastructure of Leptospira
Outer envelope (3-5 layers of peptidoglycan, alanine, glutamic acid, diaminopimetric acid, and muramic acid)
Hooked ends
Leptospira interrogans structure
- 0.15um diameter, 10um in length
- Motility depends on two endoflagella (3um) that extend along cell body
- Anticlockwise rotation: spiral shape
- Clockwise or no rotation: hooked ends
Virulent Leptospira
Antigenic structure:
>250 serovars determined by microscopic agglutination assay.
Names 4 examples of viulence determining factors:
- Soluble hemolysin
- Endoflagellum
- Metallopeptidases
- LPS target: renal tubular Na, K-ATPase and H, K-ATPase.
Leptospira interrogans disease
- Causes leptospirosis or Weil’s disease
- Zoonotic disease, of which some strains are pathogenic
- Ichterohaemorrhagiae is main serovar causing disease
Transmission of L. interregans
- Wide range of host reservoirs
- Human risk - indirect or direct contact with infected animals/animal products
- Also from soil, food and water through skin break/mucous membranes
- Readily killed by >60 degrees, detergents, desiccations and acids
Pathogenesis of L. interrogans
- Migration from blood to lungs, liver, kidneys and cerebrospinal fluid
- Causes renal injuries -> intestinal nephritis causes glomerular swelling/hyperplasia -> basement membrane thickening and renal failure
- Hepatic injuries - hepatocellular disease due to vasculitis
- Meningitis
- Symmetric pretibial rash
Clinical manifestation
Incubation period - 10-12 days - chills, fever, headache, conjunctival suffusion, myalgia, GIT symptoms
1st leptospiremic stage
Defervescence (abatement of fever)
2nd leptospiremic stage
Reside/avoid macrophages inducing high levels of cytokines which cause sepsis-like symptoms - life threatening
Leptospira invasion process
- Leptospires enter through skin breach and migrate through epidermis and dermis (collagen I/III, elastin, fibronectin, vitronectin).
- Leptospires penetrate endothelial cells layers via cell-cell junctions
Avoid immune attack using complement regulators
Secrete proteases to degrade ECM and inactivate complement system
- Endothelial cells secrete cytokines and antimicrobial peptides
Leptospires secrete haemolysins which target red blood cells
Macrophages produce ROS and RNS in defence
- Coagulation cascade activated
Plasminogen -> plasmin
Plasmin degrades fibrin/fibronectin clots, ECM and inactivates complement proteins
treatment of leptospira
- Antibiotic treatment in first 2 days after onset - Penicillin, streptomycin, tetracycline, erythromycin
- Serovar-specific vaccine
- Prophylaxis with short term/long term tetracycline
2014 Leptospira infections
76 cases
Animal (79%) and water (24%) exposure
22 cases abroad in South East Asia, Central America, Caribbean, and France
Mainly male and aged 19-67
Leptospira infections in 2010
10 infection were occupational e.g. farmers, carpenters, abattoir workers
10 infection were non-occupational e.g. fishers, postman, pets, canoeist
Explain what lyme disease is
- Discovered in 1977
- Common tick/insect-borne disease
- 300,000 Americans and 84,000 Europeans have Lyme disease
- Can affect all ages
- Oldest case was Tyrolean iceman - 5,300 year old copper aged individual
What causes Lyme disease
- Borrelia burgdorferi - bacterial spirochete
- Predominant in North America
- Infected after bitten by hard-bodied ticks (Ixodes species) which have B, burgdorferi
- Other insects may be involved
- Fully treatable if caught early, but developed infection spreads to heart, nerves and joints
B. burgdorferi characteristics
- Helical
- Periplasmic flagella
- Flagella insertion points near termini of spirochaete
- Bundles of flagella wind around flexible, rod-shaped proteoplasmic cylinder and overlap in middle
- Outer membrane constrains flagellar bundles within periplasm
- Moves along sides of blood vessels
Borrelia burgdorferi genome
- One large linear chromosome (901,725bp)
- 853 coding genes
- 21 other linear/circular plasmids (additional 533Kbp)
- Strains without complete set of plasmids unable to successfully infect host
B. burgdorferi infection plasmid
- Ip25
- B. burgdorferi pathogenesis mechanisms unknown
- Lacks iron containing enzymes and iron containing proteins in electron transport:
Uses Manganese
Circumvents body defence mechanism
4 ticks that carry lyme disease
European tick
Lone star tick
Black legged tick
Rocky mountain tick
B. burgdorferi life cycle
Unfed larva attaches to infected mouse for 3-5 days to feed
Fed larva moults for 1 month to 1 year where spirochete multiply
Unfed nymph feed on uninfected mouse, infecting the mouse as spirochaetes migrate from midguts to salivary glands
What causes lyme disease to emerge
- More deer
- Surbanization
- Climate change
- two-fold: helping ticks reproduce, helping them live in more parts of the US
Two stages of Lyme disease
Stage 1: Early stage - 3-30 days after bite:
- Flu like symptoms develop within 1-2 weeks
- Fatigue, nausea, vomiting, muscle and joint pains common
- Skin lesions appear as small red circular rash
- Secondary skin rashes appear in near 80% of individuals
Stage 2: Late stage - weeks/months after bite
- Severe headache/neck pain
- Arthritis in 60% of cases
- 15% of cases develop neurological problems e.g. psychosis
Infection cycle of B. burgdorferi
- Infected ticks feeds, where B. burgdorferi migrates from gut to salivary glands - transmitted via saliva to vertebrate host
- OspA -> OspC surface proteins to allow bacteria to flow into salivary glands
- B. burgdorferi encounters Salp15 which binds OspC, allow it’s survival against antibodies
Bartonella
- Gram -ve
- facultative intracellular parasite
- opportunistic
- Mild symptoms but severe in immunocompromised people
- Transmitted by ticks, fleas, sand flies and mosquitos
- > 37 species associated with insect vectors
- At least 8 species infect humans
