SPIROCHETES AND NEISSERIA
Dr Alvin Fox
Medical Microbiology, MBIM
650/720 Lecture: 40
Reading: Murray third edition
Chapter 41 (Spirochetes) 28 (Neisseria).
(Treponema, Borrelia and Leptospira)
Spirochetes are Gram negative
bacteria that are long, thin, helical and motile. Axial filaments (a
form of flagella) found between the peptidoglycan layer and outer
membrane and running parallel to them, are the locomotory organelles.
facts about Syphilis from CDC
Congenital syphilis, primary and secondary syphilis rates,
by year -- United States, 1992-1998. Epidemiology,
surveillance. CDC/Dr. Demetri Vacalis email@example.com
Histopathology showing Treponema pallidum spirochetes in
testis of experimentally infected rabbit. Modified Steiner
silver stain. CDC/Dr. Edwin P. Ewing, Jr. firstname.lastname@example.org
T. pallidum is generally transmitted by genital/genital contact.
Transmission in utero or during birth can also occur. Syphilis,
chronic and slowly progressive, is the third most common sexually
transmitted disease. After initial infection, a primary chancre (an area
of ulceration/inflammation) is seen in genital areas within 10-60 days.
The organism, meantime, has penetrated and systemically spread. The
patient has flu-like symptoms with secondary lesions particularly
affecting the skin (2-10 weeks later). The final stage (if untreated) is
tertiary syphilis (several years later). In primary and secondary
syphilis organisms are often present in large numbers. However, as the
disease progresses immunity controls bacterial replication and fewer
organisms are seen. It is extremely difficult to detect spirochetes in
tertiary syphilis. The systemic lesions of skin, central nervous system
and elsewhere are suggestive of a delayed hypersensitivity reaction.
The organism cannot be cultured
from clinical specimens. Thus, experimentally, syphilis is commonly
studied in animal models. Also microscopic and serological methods are
the only means of clinical diagnosis.
In primary syphilis (before
immunity develops), the organisms are often present in sufficient
numbers in exudates to be detected by dark field microscopy. In
conventional light microscopy, the light shines through the sample and
thin treponemes cannot be visualized. In dark field microscopy, the
light shines at an angle and when reflected from the organism will enter
the objective lens. The actively motile organisms appears brightly lit
against the dark backdrop. Alternatively fluorescent antibody staining
In secondary and tertiary
syphilis, serological methods are usually used to detect syphilis.
Screening methods are based on detecting serum antibodies to cardiolipin
in patients (including VDRL test). The antibodies result from tissue
injury, with autoimmunity developing to self components. Thus, there are
many other diseases that result in anti-cardiolipin antibodies and false
positives are common. However, these are cheap screening tests. More
definitive diagnosis is achieved by detecting the presence of
"specific" serum antibodies against treponemal antigens. These
tests are more expensive and usually performed (as a definitive
diagnosis) on sera previously shown to be positive after first detecting
antibodies to cardiolipin.
No vaccine exists, but antibiotic
therapy (usually penicillin G) is usually highly effective.
Rare (in the US) diseases caused
by organisms related to T. pallidum are bejel, yaws and pinta.
Yaws is a crippling and disfiguring disease affecting some 50 million
people in the world © WHO
Borrelia burgdorferi and
facts about Lyme disease from CDC
Histopathology showing Borrelia burgdorferi spirochetes in
Lyme disease. Dieterle silver stain. CDC/Dr. Edwin P.
Ewing, Jr. email@example.com
Reported cases of Lyme disease in the United States 1998 CDC
Lyme disease risk by region of United States CDC
Lyme disease is a relatively
newly recognized disease. Although clinically first described in 1975,
the role of a tick-borne spirochete was not proven until 1983. These
ticks infect a large array of wild life, particularly white footed mice.
A tick bite leads to transmission of B. burgdorferi causing an
erythematous skin rash in a few days along with a transient bacteremia
leading to (weeks or months later) severe neurologic symptoms or
polyarthritis. Cardiac problems may occur in a minority of cases. If
antibiotic therapy is initiated early, a cure is usually achieved.
However, late antibiotic administration (penicillin or tetracycline) is
The organism is highly fastidious, growing extremely slowly in tissue
culture (not bacteriological) media. The vast majority of body fluid or
tissue samples from patients with Lyme disease do not yield spirochetes
on culture. Lyme disease is thus usually diagnosed by detection of serum
antibodies to B. burgdorferi. However, acutely antibodies may not
occur in detectable titer, making early diagnosis difficult. Whilst late
diagnosis, (as mentioned above) may lead to ineffective treatment. Many
patients are unaware of having had a tick bite or a rash.
Etiology. The chronic
arthritis clinically resembles rheumatoid arthritis. Live agent is
almost never cultivated from the joint (in common with other forms of
reactive arthritis such as Reiter's syndrome and rheumatic fever).
However, small numbers of persistent spirochetes and borrelial antigens
have been detected histologically in human tissues. Whether the organism
persists in a viable form or not remains to be determined. Thus, there
is no clear explanation for the immunopathologic stimulus for chronic
tissue injury in Lyme arthritis.
There are less than 100 cases of
relapsing fever per year in US. Relapsing fever (with associated
bacteremia) is caused by other species of Borrelia which are
transmitted by tick (B. hermsii, rodent host) and lice (B.
recurrentis, human host) bites. The term relapsing fever is derived
from the following repeating cycle. As an immune response develops the
disease relapses. However, the antigens expressed change and the disease
reappears. The organism is extremely difficult to culture and there is
no serological test. The organism is generally detected by blood smear.
Scanning electron micrograph of Leptospira interrogans
strain RGA. Two spirochetes bound to a 0.2 µm filter.
Strain RGA was isolated in 1915 by Uhlenhuth and Fromme from
the blood of a soldier in Belgium. CDC/NCID/Rob Weyant
Leptospirosis in the kidney Bristol Biomedical
Archive © University of Bristol. Used with permission
There are less than 100 cases per year in US. This flu-like or severe
systemic disease is also a zoonotic infection. Leptospira are transmitted
in water contaminated with infected urine from wild animals (including
rodents) and farm animals and can be taken in through broken skin (e.g.
bathing). Leptospira particularly infect the kidney, brain and
eye. They are the most readily culturable of the pathogenic spirochetes;
but this is not routine and diagnosis is usually by serology.
are Gram negative diplococci (pairs of cocci). These bacteria grow best
on chocolate agar (so-called because it contains heated blood, brown in
color); a modified (selective) chocolate agar commonly used is Thayer
Martin. The colonies are oxidase positive (i.e. produce cytochrome
oxidase) which is demonstrated by flooding the plate with a dye which on
oxidation changes color.
N. gonorrhoeae (the
facts about gonorrhea from CDC
Neisseria gonorrhoeae - coccoid prokaryote (dividing);
causes gonorrhea (SEM x 40,000) © Dr
Dennis Kunkel, University of Hawaii. Used with permission
Positive FA test for Neisseria gonorrhoeae. This strain
was penicillin-resistant. CDC
found only in man, is the causative agent of gonorrhea, the second most
common venereal disease. The organism often causes an effusion of
polymorphonuclear cells. A smear may show the presence of Gram negative
cocci present in cells. However, culture is essential for definitive
diagnosis (go here).
A common feature of
disseminated gonoccocal disease is arthritis. Although commonly
considered a form of septic arthritis, in many cases gonococci cannot be
isolated from the joint (i.e. they are "reactive" in nature).
Dermatitis is also common.
is still usually effective. However, resistant strains producing ß
lactamases are sufficiently common that alternatives are recommended for
all gonococcal infections; this includes ceftriaxone (a ß
lactamase-resistant cephalosporin). There is no vaccine since strains
are highly variable in their external antigens (both outer membrane and
pili). Both are involved in the initial adhesion of the organism to
IgA proteases (also
produced by N. meningitidis) are involved in successful
colonization. As for many other bacterial infections, a role for both
the lipopolysaccharide and peptidoglycan in tissue injury have been
suggested. Exotoxins are not believed to be of importance in
meningitidis (the "meningococcus")
Neisseria meningitidis, group C, in spinal fluid. CDC/Dr.
Neisseria meningitidis - coccoid prokaryote (dividing);
causes meningitis and Waterhouse-Friderichson syndrome (a
fulminating meningococcal infection occurring mainly in
children under ten years old) © Dr
Dennis Kunkel, University of Hawaii. Used with permission
resides only in man. The majority of cases are sporadic cases most
commonly seen among young children. Outbreaks occur usually among adults
living in confined and crowded conditions (e.g. army barracks). Initial
infection of the upper respiratory tract (involving binding by pili)
leads to invasion into the bloodstream and from there to the brain.
Indeed, it is the second most common cause of meningitis (pneumococcus
is the most common). It is usually fatal if untreated but responds well
to antibiotic therapy. Thus, rapid diagnosis is important. The organism
is often detectable in spinal fluid (Gram negative diplococci within
polymorphonuclear cells) or antigenically. Culture on Thayer Martin (or
similar) agar is essential for definitive diagnosis. Penicillin is the
drug of choice.
antigenically and can be serogrouped with anti-capsular antibodies. The
capsule is an important pathogenesis factor allowing inhibition of
phagocytosis. A vaccine against these capsular antigens is available.
However, effective immunization against the most common group B has not
species morphologically resembling Neisseria are found in the
normal flora of the oropharynx but can be differentiated from the
pathogenic Neisseria readily. These occasionally cause
opportunistic human disease (including pneumonia).