Lyme Disease Flashcards
What is Lyme Disease?
= most common tick / insect borne disease in US/Europe
= fastest growing vector-borne infectious disease in US
= discovered in 1977
= can affect all ages
What causes Lyme disease?
= Borrelia burgdorferi
( a bacterial spirochete)
= predominant in N. america
= humans infected after being bitten by hard-bodied ticks (Ixodes species) that are infected with B. burgdorferi
(other animals that feed on animal blood may be involved also)
= if treated early: full recovery
= if untreated: infection spreads to joints, heart and nervous system
What is the Borrelia burgdorferi structure?
= helical cell shape
= periplasmic flagella
(flagellar insertion points location near termini of spirochaete)
= bundles of flagella wind around flexible, rod-shaped cyclinder of Borrelia and overlap in the middle
= outer membrane consrains the flaggelar bundles within the periplasm
How does B. burgdorferi move in blood vessels?
= can move along sides of blood vessels to spread throughout body
(without getting swept away by force of rushing blood)
= has catch bonds - protein called BBK32
Why is the B. burgdorferi genome unique?
One large linear chromosome
= with ~853 coding genes
Then also 21 other linear / circular plasmids
= unusually high number of plasmids
Some strains that lack a complete set of plasmids
= unable to successfully infect host
= e.g. Ip25 found necessary for Borrelia infection
Sequenced genome does NOT contain any obvious genes coding for pathogenesis
= mechanisms of B. burgdorferi infections are unknown
Lacks iron containing enzymes + iron containing proteins in electron transport
= uses manganese instead
= circumvents bodies defence mechanisms
Which ticks carry Lyme disease?
European Tick
= Ixodes ricinus
Black-legged Tick (USA)
= Ixodes scapularis
Rocky Mountain Tick (USA)
= Dermacentor andersoni
Lone Star Tick (USA)
= Amblyomma americanum
What is the B. burgdorferi life cycle?
= Uninfected larval ticks acquire B. burgdoreferi by feeding on infected small wild mammals (mainly rodents)
= Spirochaetes multiply and persist in midguts of infected ticks through the moult to the nymphal stage
= When infected nymphal ticks feed, the spirochaetes migrate from midguts to salivary glands
= Can then be transmitted to a naive mammalian host
What are some reasons for the rise in Lyme disease incidence?
Moor deer
Surbanisation (living closer to animals)
Climate change
= helps ticks reproduce, live in more areas
What are the signs and symptoms of Lyme disease?
Stage 1 (Early stage)
= 3-30 days after bite
= flu-like symptoms within 7-14 days
= headache, fever, chills, muscle / joint pain, mausea, vomiting, dizziness, non-productive cough
= skin lesions may appear as small red circular rash around bite, expands (Erythema migrans)
(= penetration of vessels and dissemination)
Stage 2 (Late stage)
= weeks or months after initial onset
= sever headache and neck pain or stiffness
= arthritis develops in 60% of patients
= 15% develop neurological symptoms = psychiatric problems
(=penetration of tissues and establishment of infections in heart, joints and skin, carditis, arthritis and facial palsy may occur)
What is the infection cycle of B. burgdorferi?
Changes gene expression in response to environment
= produces specialised outer surface lipoproteins for protection
= attaches itself to tick’s salivary immunosuppressive proteins to protect against host’s immune system
Lipid proteins - Osp-type
= help bacterium establish colonies of itself within the host
= OspA prevents the bacterium to be injected
Decreasing OspA
= allows detachment from gut to flow into tick’s salivary glands
(with help of protein OspC)
B. burgdorferi encounters tick protein: Salp15 in salivary glands
= Salp15 binds to OspC
In presence of neutralising antibodies from immune vertebrate host
= B. burgdorferi with OspC and Salp15 on surface preferentially survive
(compared to those without OspC / Salp15)
What is an example of future treatment option?
= lyme disease vaccine (clinical trials)
= new hexavalent, protein subunit-based vaccine that targets OspA
= could provide protection against most Borrelia species
BUT new pathogenic species being discovered
= e.g. Borrelia mayonii causes lyme disease with unusually high spirochaetemia
What is Bartonella spp?
= gram-negative bacterium
= only genus in family Bartonellaceae
= facultative intracellular parasite
= opportunistic pathogen
Infections
= generally mild but can be severe in immunocompromised patients
= transmitted by ticks, fleas, sand flies, mosquitoes
= >37 species associated with insect vectors
(~8 infect humans)
What are some examples of Bartonellosis infections?
Cat scratch disease (Bartonella henselae)
= resolves spontaneously in 2-4 months
= red spot at bite site (1-3 weeks)
= lymph nodes swell
= headache, fever
Carrion’s disease (Bartonella bacilliformis)
= two stages
1. sudden, acute phase (Oroya fever)
2. chronic, benign skin (cutaneous) eruption consisting of raised, redish-purple nodule (Peruvian warts)
Trench fever (Bartonella quintana)
= sudden fever (4-5 days), chills, weakness, headache, dizziness, leg and back pain
= temporary skin rash
= enlargement of liver / spleen
= usually self-limiting, but can relapse / be chronic
Can have Bartonella spp associated:
= skin disease (bacillary angiomatosis)
= liver (peliosis hepatis)
= heart (endocarditis)
= eyes (neuroretinis)
= blood (bacteriermia)
= brain (encephalitis)
What are some Bartonella virulence factors?
Trimeric autotransporter adhesins
= e.g. BadA, Vomps
= stable interaction with host cell as basis for further manipulation, secretion of proangiogenic cytokines
Outer membrane proteins
= secretion of MCP-1 and upregulation of E-selectin and ICAM-1
VirB/D4 type IV secretion system
= setup and control of intracellular niche
Secreted factor - GroEL
= inhibition of apoptosis and mitogenic stimulation of host cells
Trw tpe IV secretion system + Deformin
=enabling erythrocyte invasion
Flagellation + Invasion-associated locus
= invasion of erythrocytes
LPS
= immune evasion and immunomodulation
Hemin binding proteins + OMP43
= ? host cell adhesion
What is the link between Lyme disease and Bartonella?
Bartonella spp has been identified in various tick species
= symptoms often overlap with Lyme disease
= under-reported
60% of chronic Lyme disease patients
= report co-infections
(Bartonella is 2nd most common co-infection)
