The spirochaetes Flashcards
Definition
Very unusual bacteria: Gram-negative Very thin- viewed by dark-field microscopy or EM Spiral shape Varied genome size Many plasmids (large) Virulence factors poorly understood Unique method of motility via internal flagella
Properties
Anaerobic, fastidious, slow growing
Many difficult to grow or unculturable- T. pallidum
Laboratory diagnosis
often relies on serological or immunofluoresence tests
Spirochaete taxonomy
- Recognised by cell shape
- Identification by Sequence analysis of 16s rRNA gene
Cell structure, motility and flagella
Inextricably linked
In most bacteria the cell shape is defined by a combination of the peptidoglycan layer and the bacterial cytoskeleton.
For Spirochaetes this is also defined by internal flagella commonly known as axial filaments
Deletion of flagella assembly genes (flaB and flgE) results aflagellate non-motile strains
-these strains are no longer corkscrew-like
-they become straight rod shaped cells.
-occurs for both Treponema denticola and Borrelia burgdoferei
Species identification by 16s rRNA sequencing
16s rDNA gene well conserved due to essential function
Acts as molecular clock and species signature as evolves slowly in time
We sequence it to speciate bacteria
How do they swim
Counter-rotation of the internal flagella filament bundles results in rotation of the cell body
Rotation of the body results in burrowing motility of spirochaetes
The spirochaete cell surface
Cell wall components able to modulate immune response, known as Major sheath proteins (Msp)
No LPS - glycolipids
Spirochaete diseases
Leptospira: Weils disease, Leptospirosis
Borrella: Lyme disease, relapsing fever
Treponema: Syphilis, ANUG, periodontitis
Zoonotic infections
Both Lyme disease and Weil’s disease are good examples of zoonotic infections (like plague)
They have an animal reservoir of infection that can under certain circumstances infect humans via a zoonotic vector
Zoonotic infections
Both Lyme disease and Weil’s disease are good examples of zoonotic infections (like plague)
They have an animal reservoir of infection that can under certain circumstances infect humans via a zoonotic vector
Lyme disease
Caused by Borrelia burgdoferi and related sub-species
Most common zoonootic bacterial infection in Europe and North America.
Small spirochete only viewed by EM and Dark-field microscopy
Nutritionally fastidious Anaerobe
Zoonotic reservoir - Lyme disease
Transmission via Ixodes spp. Ticks
NOT INSECTS- 8-legs!
Ectoparasites of many vertebrate species: rodents, deer, birds
Three life-cycle stages
Feed once in each stage: 3-5 days per feed
Bacteria live and multiply in midgut of ticks and are transmitted via saliva after biting humans- 36h attachment!
Infection of Humans - lyme disease
Rodents –> hard lxodes tick (–> deer)
Tick bite –> infected human, no further spread
Stages of infection of Lyme disease - acute
After biting Flu-like symptoms often seen
a localised rash: Erythema migrans present in 30% cases
This is a characteristic bulls-eye rash
Other lesions at sites distal from innoculation occur in 50% of patients
Later stages of lyme disease infection
Seen from 1 week to 2 years post-infection:
- Neurologic: Meningitis, encephalitis, peripheral neuropathy, cranial-nerve (facial) palsies, vision impairment (chronic)
- Cardiac: myocarditis, blockages
- Athralgia and arthiritis- may persist for months or years- often debilitating- possible autoimmune component – reactivity to surface proteins (OspA)
Causes of later symptoms of lyme disease
Caused when bacteria enter sites other than bloodstream - such as neurons and joints
Borrelia burgdoferi mechanism/ virulence factors
Motility considered a major virulence factor
Invades epithelial cells
Capable of invading many tissue types
No LPS, but numerous Outer membrane lipoproteins OspA-D, expressed at different points in infection cycle. Vls proteins- variable suface proteins- antigenic shift
DbpA- Decorin binding protein, host mimicry?
Copes with low-iron levels by using Manganese instead of iron as an enzyme co-factor
Treatment of Lyme disease
Long courses of antibiotics
doxycycline
Chronic infections hard to treat since bacteria become metabolically inert and reside in sites refractory to treatment.
Prevention of Lyme disease
Vaccine:
-to OspA only partly effective: OspA is not expressed by Borrelia in humans, only in the tick.
-some side-effects, also might stimulate autoimmune disease- since many symptoms may be due to autoimmunity
Avoidance of endemic areas
Clothing, DEET based repellents
Relapsing fever
Borrelia recurrentis
Transmitted via ticks and human body louse
Repeated febrile illness
Initial infection cleared, but antigenic variation by the bacterium starts a new set of symptoms
3-10 episodes
Can infect liver/ spleen
How could it relapse?
Antigenic variation- surface protein OspC multiple copies- expressed variably in recurring infecitons
Prevention and control of relapsing fever
CDC: since most cases occur after sleeping in rodent infested cabins- check for mice etc!
Leptospirosis and Weils disease
Caused by Leptospira interrogans Leptos (Gr) – ununusually thin spira (la) - colied, spiral Two terminal Periplasmic flagella Present in stagnant water and rivers Infects many mammals Dogs and Rats most important zoonotic reservoir (urine) Enter via broken skin 40- 60 cases/ year in England Outbreaks in walkers, triathlon runners! (WHY????), but many imported cases
Symptoms of leptospirosis and Weil’s disease
1-2 week incubation in blood
Leptospirosis: Febrile, flu-like illness with muscle pain, reddening of eyes, and other symptoms such as diarhoea and in some cases meningitis and Hemorrhage in Aqueous humour of eye and CSF
10-15% of cases develop Weil’s disease:
-kidney failure
-jaundice and liver failure
Most symptoms caused by damage to blood vessels
Prevention and treatment of leptospirosis and Weil’s disease
Rodent control
Doxycycline
Avoid swimming in infected rivers
ANUG
Acute necrotisinig Ulcerative Gingivitis
‘Trench Mouth’ or Vincents disease
Was common in WW1 soldiers
Thought to be caused by bacterial complex involving oral spirochaete Treponema Vincentii (but not just that)
Treated by metronidazole or Hydrogen peroxide washes
Treponema denticola, red complex organisms and periodontitis
These three organisms are the most commonly found bacteria in periodontal cases.
-together contribute to the symptoms seen
P gingivales, T. forsythia, T. denticola
T. denticola: virulence
Adherence to basement membrane proteins via 53 Kda Msp : fibronectin, laminin, fibrinogen, type IV collagen and gelatin
Proteases, sialidases, motility, co-adherence
Proteases (T. denticola)
In-keeping with other periodontal pathogens
CTLP- Chymotrypsin like Protease (Dentilisin), surface exposed in outer membrane: Cleaves transferrin, fibrinogen, fibronectin, IgA, IgG, gelatin
Sialidases (T. denticola)
Cleaves surface sialic acid from human cells/ saliva- mutant reduced infection in mice
Motility (T. denticola)
might also contribute to tissue invasion and disease progression
Co-adherence (T. denticola)
with other oral bacteria in mixed biofilm also important (i.e. Pg, Tf, and Fuso’s)
Syphilis: T. pallidum
Major venereal disease for at least last 600 years
Originally known as the ‘french disease’ (morbus gallica) – 1495… french army
Modern name coined by Italian poem in which boy is punished by god
Treatment with Mercury
‘ A night in the arms of Venus leads to a lifetime on Mercury’
Other treponemal diseases
Yaws: T. pertenue - early skin lesions that clear - later destrucitive lymph and bone - south america and central africa Pinta: T. carateum - again early skin lesions - these progress to chronic disfiguring lesions over time - south and central america Skin- to- Skin transmission -treatable with penicillin
