GRAM-POSITIVE BACILLI I Spore-forming bacilliNon-spore-forming bacilli Bacillus anthracisCorynebacterium diptheriae Bacillus cereusListeria monocytogenes

GRAM-POSITIVE BACILLI I

Spore-forming bacilli Non-spore-forming bacilli

Bacillus anthracis Corynebacterium diptheriae

Bacillus cereus Listeria monocytogenes

Actinomyces

BACILLUS ANTHRACIS

1915 German agents in the US believed to have injected horses, mules and cattle with anthrax on their way to Europe during World War I

1937 Japan starts biological warfare program in Manchuria

1942 UK experiments with anthrax at Gruinard Island off the coast of Scotland (only recently decontaminated)

1943 United States begins developing anthrax weapons

1945 Anthrax outbreak in Iran kills 1 million sheep

1969 US biological weapons program ends

1972 International convention outlaws development and stokpiling of biological weapons

1978-80 Human anthrax epidemic in Zimbabwe infects 6,000 and killing 100

1979 Aaerosolized anthrax spores are released accidentally at a Soviet Union military facility, killing 68 people

1991 US troops vaccinated for anthrax in preparation for Gulf War

1995 Iraq admits it produced 8,500 liters of concentrated anthrax

1998 Anthrax vaccination approved by for all military service members

BACILLUS ANTHRACIS

Form spores aerobically

Prominent polypeptide capsule composed ofD-glutamate residues

Capsule is antiphagocytic

Antibodies against capsule are not protective

Micrographs of anthrax bacilli taken by Robert Koch, who confirmed the bacterial origin of anthrax in 1876

Spore formation in Bacillus

Mucoid type colonies of encapsulated Bacillus

Bacillus anthracis capsule visualized by India Ink negative stain

BACILLUS ANTHRACIS

Pathogenesis

Virulence factors:

Capsule composed of poly-D-glutamic acid

Anthrax toxin

“Anthrax toxin” consists of 3 proteins encoded by a large plasmid, pXO1

1. Protective antigen (PA)

2. Lethal factor (LF)

3. Edema factor (EF)

Non-toxic individually

Protective antigen (PA) facilitates cell entry of the other toxins.

Binds to 2 types of receptors on cell surfaces:

Tumor endothelial marker 8 (TEM8) (anthrax toxin receptor) and Capillary morhpogenesis protein

Present on cells in the heart, brain, intestine, lung, skeletal muscle, pancreas, macrophages

After receptor binding, PA is cleaved by cellular proteases, and forms a heptameric “prepore”

LF or EF bind to the heptamer and are endocytosed

In the acidified endosome, the prepore transforms into a pore, releasing the factors into the cell

Lethal factor

A zinc metalloproteaseCleaves the phosphokinase that activates the

mitogen-activated protein kinase (MAPK) signal transduction pathway

Cleavage of phosphokinase inhibits cell growth 3. Edema factor: An adenylate cyclase dependent on protective antigen for binding and entry into the cell

Edema factor

An adenylate cyclase

Increases intracellular cAMP

Related to the enzyme produced by Bortedella pertussis and Pseudomonas aeruginosa

BACILLUS ANTHRACIS

Transmission

Through exposed skin or mucous membranes, from contaminated soil or infected animal products or by contact with sick animals

Inhalation: rare in humans, more common in herbivores

BACILLUS ANTHRACIS

Clinical syndromes

Cutaneous anthraxSpores entering abrasions in the skinPainless ulcer with a black eschar (scab)Local edemaCalled "malignant pustule"Can lead to death in 20% of patients if untreated

BACILLUS ANTHRACIS

Clinical syndromes

Inhalation anthrax(pulmonary anthrax, "Woolsorter's disease”)Initially appears like a viral respiratory illnessCan progress to diffuse pulmonary disease with

respiratory failureMortality rate is high (>95% if untreated)

Treatment and control

Early antibiotic treatment of anthrax is essentialCiprofloxacin is the drug of choice

Penicillin, doxycycline, erythromycin, or chloramphenicol may be used if susceptible

Vaccination of animal herds and people in endemic areas

Burning or burial of animals that die of anthrax

BACILLUS ANTHRACIS

BACILLUS CEREUS

Causes:

Food poisoningGastroenteritisOcular infectionsIntravenous catheter-mediated sepsis

BACILLUS CEREUS

Pathogenesis

Spores can survive in soil Heat stable enterotoxin: Acts as a superantigen

Causes gastroenteritis with vomiting

Heat labile enterotoxin: ADP-ribosylates a G protein > stimulates adenylate cyclaseCauses the diarrhea and fluid loss

Transmission and clinical syndromes

Ingestion (food poisoning)Emetic (vomiting) form caused by

contaminated riceHeat-resistant spores survive and germinate Nausea, vomiting, and abdominal cramps

Diarrheal formTransmitted via contaminated meat, vegetables

or sauces

BACILLUS CEREUS

Treatment & Prevention

Symptomatic treatment

Proper refrigeration of food

Rice should not be kept warm for long periods

BACILLUS CEREUS

BACILLUS

Bacillus species used in sterilization monitoring

B. stearothermophilus sporesMonitoring proper sterilization in an autoclave 121-132oC for 15 minThen placed in medium at 37oC to grow

B. subtilis sporesMonitoring sterilization by dry heat171oC for 1 h or 160oC for 2 h

CORYNEBACTERIUM DIPHTHERIAE


Club-shaped (wider at one end) rods

Form short chains or clump together

Aerobic or facultatively anaerobic

Causes respiratory and cutaneous diphtheria


Pathogenesis

Exotoxin secreted by the bacterium

The "tox" gene introduced into strains ofC. diphtheriae by a lysogenic phage(beta phage)


Exotoxin

B subunitreceptor binding domainmembrane translocation domain

A subunitADP-ribosylation of elongation factor 2 (EF-2)




Transmission

Inhalation of airborne droplets

Skin contact at the site of a pre-existing lesion

Humans are the only natural host


Clinical syndromes

Respiratory diphtheriamalaise, sore throatexudative pharyngitislow-grade feverthick "pseudomembrane”

bacteria, lymphocytes, plasma cells, fibrin, dead cells

may cause airway obstruction



Clinical syndromes

Cutaneous diphtheriaentry into subcutaneous tissue through breaks in

the skinpapule which evolves into a non-healing ulcer

sometimes covered with a grayish membrane



Early administration of diphtheria antitoxin

Penicillin G or erythromycin to eliminate the organism and terminate toxin production

Active immunization with diphtheria toxoid during childhood (as part of the DPT vaccine) and with booster shots every 10 years

LISTERIA MONOCYTOGENES

Non-spore forming

Facultatively anaerobic small coccobacilli

Causes meningitis and bacteremia

Found in water, soil and the GI tracts of humans and animals



Human disease restricted to

neonates and the elderly

pregnant women

immunocompromised patientsdefective cell-mediated immunity


Pathogenesis

Can grow in macrophages and epithelial cells

Virulent strains produce listeriolysin O, a hemolysin Phospholipase C

Can replicate at 4-8 oC

Growth at 4˚C


TransmissionContaminated food

milk, soft cheese, undercooked meat, unwashed raw vegetables, cabbage

From bacteremic mother to fetusThe incidence of disease in AIDS patients is 100-

fold greaterMortality rate (20-30%) higher than most other food-

borne diseases.


Clinical syndromesNeonatal diseaseEarly onset disease (granulomatosis infantiseptica)

acquired transplacentally in uterodisseminated abscesses and granulomas in multiple tissues

Late-onset diseaseacquired soon after birthmeningitis or meningoencephalitis

with septicemia


Clinical syndromesDisease in adults

mild, influenza-like illness in healthy adultssevere illness in immuno-compromised patients meningitisshould be suspected in organ transplant patients,

patients with cancer, or pregnant women developing meningitis

bacteremiahigh-grade fever and hypotension in acute cases



Penicillin or Ampicillin, either alone or with gentamicin

Trimethoprim-sulfamethoxazole

Avoid raw or partially cooked foods of animal origin, soft cheese or unwashed raw vegetables

ACTINOMYCES

Delicate filamentous forms (hyphae)Actinomyces = "ray fungus" (Gr.)Gram-positive bacilliFacultative anaerobic or strict anaerobic

Form long branching filaments (not acid-fast)

Produce slowly-developing chronic infections

Most human infections are caused by Actinomyces israelii

Actinomyces

Gram stain of Actinomyces in pus

Sulfur granule (filamentous organisms bound by calcium phosphate) collected from the sinus tract of a patient with actinomycosis

Actinomyces

Macroscopic colony Gram stain

“Molar tooth” appearance of a colony ofActinomyces israelii

Pathogenesis

Cause opportunistic infections ofupper respiratory tractgastrointestinal tractfemale genital tract

when normal mucosal barriers are disrupted

Actinomycosis is characterized by multiple abscesses connected by sinus tracts

Actinomyces

Epidemiology

Endogenous infection

Cervicofacial actinomycosis may occur after dental procedures

The dentist may be the first to diagnose the swelling due to this condition

Thoracic actinomycosis is established via inhalation or via the bloodstream

Actinomyces

Epidemiology

Abdominal infections usually caused by surgery or trauma

Pelvic infections may result from abdominal infections or intrauterine devices

Central nervous system infections spread from other locations

Actinomyces

Actinomyces has colonized the surface of an intrauterine device, leading to the development of

pelvic actinomycosis

Cervicofacial actinomycosis


Surgical debridement and long-term administration of penicillin G (or tetracycline, erythromycin or clindamycin)

An undrained focus must be suspected if If infections do not respond to prolonged therapy

Good oral hygiene is necessary for prevention Antibiotic prophylaxis before oral operations

Actinomyces

Documents

GRAM-POSITIVE BACILLI I Spore-forming bacilliNon-spore-forming bacilli Bacillus anthracisCorynebacterium diptheriae Bacillus cereusListeria monocytogenes