The Spirochetes and Lyme disease and Syphilis

how was lyme disease first described as

that it was vector borne disease because of geographic distribution and seasonality

what is lyme diease’s causative agent?

borrelia burgdoferi

What is the gram stain structure of Lyme disease

because of their poor stain, they are gram negative with Spirochete morphology

• stain better with Giemsa or Wright’s

what does it mean for lyme disease to be a microaerophile

• it has slow generation time (12 to 24 hours)

• somewhat fastidious

• must be grown on medium supplemented with rabbit serum

what are the general characteristics of borrelia burgdorferi

• the individual bacteria tends to have 5-7 coils

• it is embedded outside the cell wall but under an outer envelope are 7-20 periplasmic flagella ( endoflagella)

• they give rise to characteristic twisting motility and may help penetrate tissues

how complete is borrelia burgdorferi’s genome?

it has complex genome

• 22 DNA molecules

• main chromosome is linear as are the most of the plasmids

• this is rare for bacteria

what is vector Ixodes sp.

the US distribution is mainly focused on Northeast and Upper Midwest

• has 3 life stages, larvae, nymph, and adult

• they must have blood meal for each transition

• preferred hosts are white tailed deer and white footed mouse

• deer cant transmit infection to tick but rodents can

• transovarial (verticle) transmission is rare

what is the natural host of borrelia burgdoferi: pyromyscus leucopus

is a white footed mouse

• earlier tick stages favor this host

what is the natural host for borrelia burgdoferi: odocoileus virginianus

is a white tailed deer

• adults tend to feed on deer, mate and then dro off to lay eggs on ground

• there is no evidence either wild host gets detectable disease from infection

what is the transmission cycle of borrelia burgdoferi

1. adult tick females drop off host to lay eggs

2. eggs hatch into a six legged larvae

3. larvae attach to and feed on first host and may acquire B.burgdoferi

4. larvae tick molt into nymphs after leaving first host

5. Nymphs attach to and feed on second host and may acquire B.burgdoferi

6. nymphs molt into adults after leaving second host

7. adults attach to the third host for feeding and mating

8. Infected nymphs feed on humans, transmitting B.burgdoferi

9. Infected adults feed on dogs and sometimes humans, transferring B/burgdoferi

what are the 3 phases that Lyme disease is divided into

early local, early disseminated, and late disseminated

• early local is 3 to 30 days post tick bite

what are the classic signs of early local stage of lyme disease

erythema migrans, a red expanding rash that develops an area of clearing behind the expansion front, giving a “bulls eye” appearance

• they may grow to 12 inches across and are rarely painful or itchy but may be warm to the touch

wha are the other general symptoms of early local lyme disease symptoms

fever, chills, muscle ache, swollen lymph nodes, fatigue, headache, joint pains

what is the early disseminated stage of lyme disease ( symptoms)

multifocal erythema migrans

• represents the areas of the skin that have been colonized by the bacteria

• neurological symptoms can include Bell’s Palsy where muscles on one or both sides of the face become paralyzed

• assymetric swelling of major joints can occur

• severe headache and stiff neck indicating a meningitis as well as shooting, sleep interfering pains can appear

• heart palpitations can occur

what are the symptoms of late disseminated stage of lyme disease

moths to years post bite

• if left untreated, patients will suffer bouts of arthritis in major joints ( knees particularly)

• small amount develops various neuropathies including chronic shooting pain, numbness, or tingling sensations in the hands and feet

• may also suffer short term memory loss

• even some can develop post-treatment lyme disease syndrome in absence of any sign of continuing infection

how are the two proteins bba64 and bba07 important?

they localize to the ip 54 plasmid which is important for tick to mammal transmission

• targeted distribution of this gene prevents infection from tick bite but mice can still be infected if mutant is injected with needle

what is LMP1

is a bacterial surface protein that is highly expressed at early stages of infection

• deleting mutants have trouble setting up persistent infection and cause reduced disease in experimental animals

• mutants seem more susceptible to presence of antibodies, though complement isnt involved

what is the outer surface protein A ( OspA)

it binds to and collects on the surface of the bacterium host-derived plasminogen

what is plasminogen

is a 92kDa protein that is converted by tissue-type plasminogen activator or urokinase-type plasminogen activator into plasmin

what is plasmin involved in

in many host processes including tissue remodeling and wound healing

• it causes degradation of host extracellular matrix proteins such as fibronectin, vitronectin, and laminin

• it helps bacteria invade and colonize tissues and the coating of host proteins may even help disguise bacteria as “self”

what are the complement regulator acquiring surface proteins CRASPs

• there are 5 of those ( CRASP-1 to CRASP-5)

• they block complement activation

what happens with the virulence factor protein OspA

OspA is highly expressed when B/burgdoferi is persistently infecting starving ticks

• it binds to a protein TROSPA that is found on the surface of the tick’s midgut

• when the tick feeds, OspA expression is temporarily down regulated which allows the bacterium to mobilize within tick

what happens when OspA is downregulated?

OspC is up-regulated

• this protein allows penetration of Borrelia into tick salivatory tissues

• this change in expression takes 24-48 hours

• OspC binds to a soluble tick salivary gland protein salp15 which is immunoprotective

how does OspA helps the bacteria?

it helps it stick to the walls of the tick gut so they are not expelled and they can stay and multiply

• increase and temp and drop in pH is associated with blood meal trigger drop in OspA and increase in OspC which preps the bacterium for transmission to mammalian host

• OspC helps with migration to tick salivary gland and binding to Salp15 tick salivary protein will assist bacterium in new home

how does Salp 15 bind to DC

thru DC-SAGN protein and MAP kinase pathway suppresses TLR-Induced cytokine production that suppresses DC ability to activate T cells

what happens when Salp15 is bound to OspC at bacterial cell surface

it prevents formation of complement membrane attack complex

what is the general mechanism of evasion?

the pathogen survives by constantly changing it’s surface “coat” to stay one step ahead of the immune response

what is the medical prevention of lyme disease

lyme disease is treated with antibiotics

• like tetracyclins, paniccilins, and macrolides

• a post-treatment syndrome can develop that includes persistent syndromes of lyme disease, but those are autoimmune is nature and arent ameliorated by antibiotics

what is the personal prevention of lyme disease

• ticks can pop up whenever its above freezing

• avoid wooded and bushy areas, tick leaf litter, and tall grass

• use insect repellents

• keep skin covered, wear light clothing, tuck pant legs into socks

what are the properties of treponema pallidum

• it appears tightly coiled spirochetes with 3 periplasmic flagella

• small genome with less than 1000 genes

• consequence is highly dependent on host and so far impossible to maintain in continuous culture

• we dont know much about virulence factors

• outer membrane is mostly devoid of proteins which probably makes the bacterium of limited visibility to the immunity system

• is able to avoid phagocytosis and have the ability to adhere to fibronectin allowing association with host tissues

the epidemiolgy of syphilis

is most acquired thru sexual contact

• transmitted vertically thru placenta, thru kissing and touching an active lesion, transfusion of fresh blood, needle stick, or nursing

what are the three phases of syphilis

primary, secondary, late phases

what is primary syphilis

• first sign is chancre, a painless ulcer

• there is no bleeding or other exudate, unless there is a secondary infection

• this represents the initial site of entry for the bacterium, absence of detectable lesion is impossible

where does syphilis mainly found on

on external genitalia, but can appear on the mouth, cervix, perianal and anal areas

• enlarged regional lymph nodes usually accompany chancre

• chancre heals on its own in 3-6 weeks

• treponema organisms are already int he blood by now, treatment is still required despite of primary lesion

what is secondary syphilis

• begins 2-8 weeks after appearance of chancre

• presentation is usually clinically florid but highly variable

• easily recognized lesions involve skin

• macular lesions appear first on trunk and then spread to extremites and may become papular

• such lesions on the palms of hands and soles of feet suggest syphilis

• symptoms include fever, malaise, pharyngitis, anorexia, weight loss, arthralgia and painless lymphadenopathy

what are neurological symptoms of secondary syphilis

• CNS becomes involved in most infected

• headache, meningismus, increased CSF protein levels and meningitis can occur

• cranial nerves can be affected with facial muscle weakness, hearing loss, tinnitus and visual loss sometimes

late or tertiary syphilis

• 5-30 years after initial infection

• is a progressive destructive inflammatory disease that can attack any organ

• is divided into 3 manifestations

what are the three manifestations of late syphilis

neurosyphilis, cardiovascular syphilis, and gummatous syphilis

what are the symptoms of late neurosyphilis

• invades the brain and spinal cord

• abnormal gait, blindness, dementia, headache, muscle weakness, numbness, psychosis, memory loss seizures, tremors

late cardiovascular syphilis

• for late stages, is most common presentation

• pathology often centers on that aorta

• damage can be severe enough to cause aneurysms

late gummatous syphilis

• a type of granuloma, and can appear in many types of chronic infection

• foci of infection are surrounded by cells of the immune system

• are unable to kill the invader so they attempt to wall it off

• have swollen, rubbery texture and contain necrotic center

• can appear on the body surface or may develop internally

what is the syphilis treatment

penicillin G, azithromycin, doxycyclin and tetracyclin