Bacillus Spore-Forming Rods: Anthrax & Food Poisoning PDF

Spore-Forming Gram-Positive Rods Bacillus spp Dr. Nada A. Abdelrahim 1  Two Medically important Bacillus species: ❖Bacillus anthracis ❖Bacillus cereus 2 3 Bacillus anthracis 4  Disease Spectrum Bacillus anthr...

Spore-Forming Gram-Positive Rods Bacillus spp Dr. Nada A. Abdelrahim 1  Two Medically important Bacillus species: ❖Bacillus anthracis ❖Bacillus cereus 2 3 Bacillus anthracis 4  Disease Spectrum Bacillus anthracis causes Anthrax Anthrax is common in animals, but Rare in humans Human disease occurs in 3 main forms: Cutaneous Anthrax Pulmonary (inhalation) Anthrax Gastrointestinal Anthrax In 2001, an outbreak of both inhalation and cutaneous anthrax occurred in the US. The outbreak was caused by sending spores of the organism through the mail. There were 18 cases, causing 5 deaths in this outbreak 5  General Characteristics B. anthracis is a Large Gram-positive Rod, with Square Ends, frequently found in Chains It has a unique antiphagocytic capsule (composed of d-glutamate; other bacteria has polysaccharides capsules) B. anthracis is Non-motile (other members of the genus are Motile) Anthrax toxin is encoded on one plasmid The polyglutamate capsule is encoded on a different plasmid 6 7  Transmission Spores of B. anthracis persist in soil for years Humans are most often infected Cutaneously (at the time of trauma to skin --- allowing spores on animal products [such as hides, bristles, wool] to enter) Spores can also be Inhaled into the Respiratory Tract Pulmonary (inhalation) Anthrax: occurs when spores are inhaled into the lungs Inhalation anthrax is not communicable from person to person (despite severity of infection) 8  After being inhaled into the lung, the organism moves rapidly to the mediastinal lymph nodes, where it causes hemorrhagic mediastinitis Because it leaves the lung so rapidly, it is not transmitted by respiratory route to others Gastrointestinal Anthrax: occurs when contaminated meat is ingested 9  Pathogenesis Pathogenesis is based primarily on the production of two exotoxins (collectively known as Anthrax Toxin) The two exotoxins (Edema Factor and Lethal Factor) each consist of two proteins in an A–B subunit configuration The B (Binding subunit) in each of the two exotoxins is Protective Antigen The A (Active subunit) has enzymatic activity ❖ The name Protective Antigen refers to the fact that antibody against this protein protects against disease 10  Exotoxin Edema Factor: is an adenylate cyclase that causes an increase in intracellular concentration of cyclic adenosine monophosphate [AMP] (this causes an outpouring of fluid from the cell into the extracellular space (manifests as edema) (similar action to that of cholera toxin) Exotoxin Lethal Factor: is a protease that cleaves phosphokinase that activates mitogen-activated protein kinase (MAPK) signal transduction pathway (this pathway controls the growth of human cells, and cleavage of the phosphokinase inhibits cell growth) Protective Antigen forms pores in the human cell membrane that allows Edema Factor and Lethal Factor to enter the cell 11  Clinical Findings 1. Cutaneous Anthrax Typical lesion is: painless ulcer with black eschar (crust, scab) (see next slide) Local edema is striking The lesion is called a Malignant Pustule Untreated cases progress to bacteremia and death 12 13 Cutaneous Anthrax acquired in Eastern Turkey. Anthrax lesion at the day of presentation: (a) top view, (b) lateral view 14 Anthrax lesion on the third day of treatment: (a) top view, (b) lateral view Patient was started on amoxicillin-clavulanic acid 3gr/day. Three days later, swelling decreased 15 Typical Anthrax Eschar: After ten days of treatment, typical anthrax eschar with sharp-edged, black ulcer in the middle of the wound appeared, antibiotic was stopped 16  2. Pulmonary (inhalation) Anthrax “Woolsorter’s Disease” Begins with nonspecific respiratory tract symptoms resembling influenza, especially dry cough and substernal pressure This rapidly progresses to Hemorrhagic Mediastinitis, Bloody Pleural Effusions, Septic Shock, and Death Although the lungs are infected, the classic features and X-ray picture of pneumonia are not present Mediastinal widening seen on chest X-ray is an important diagnostic criterion Hemorrhagic Mediastinitis and Hemorrhagic Meningitis are severe life- threatening complications 17  3. Gastrointestinal Anthrax Symptoms include: vomiting, abdominal pain, and bloody diarrhea 18  Laboratory Diagnosis Smears show Large, Gram-positive Rods in Chains Spores are usually not seen in smears of Exudate (because spores form when nutrients are insufficient. Nutrients are plentiful in infected tissue) Non-hemolytic colonies form on Blood agar Aerobically ❖ In case of a bioterror attack, rapid diagnosis can be performed in special laboratories using PCR–based assays Another rapid diagnostic procedure is the: Direct Fluorescent Antibody test that detects antigens of the organism in the lesion Serologic tests, such as an ELISA test for antibodies, require acute and convalescent serum samples and can only be used to make a diagnosis retrospectively 19 20 21 22 Treatment Ciprofloxacin is the drug of choice Doxycycline is an alternative drug No resistant strains have been isolated clinically 23  Prevention ❖ Ciprofloxacin or Doxycycline was used as prophylaxis in those exposed during the outbreak in the United States in 2001 People at high risk can be immunized with cell-free vaccine containing purified protective antigen as immunogen The vaccine is weakly immunogenic, and six doses of vaccine over an 18- month period are given Annual boosters are also given to maintain protection Incinerating animals that die of anthrax, rather than burying them, will prevent the soil from becoming contaminated with spores 24 Bacillus cereus 25 Disease Spectrum Bacillus cereus causes Food Poisoning 26  Transmission Spores on grains such as rice survive steaming and rapid frying Spores germinate when rice is kept warm for many hours (e.g., reheated fried rice) Portal of entry is the gastrointestinal tract 27  Pathogenesis Bacillus cereus produces two enterotoxins Mode of action of one of the enterotoxins is similar to that of cholera toxin (i.e., it adds adenosine diphosphate ribose [ADP-ribosylation] to a G protein, which stimulates adenylate cyclase and leads to an increased concentration of cyclic AMP within the enterocyte) Mode of action of the other enterotoxin resembles that of staphylococcal enterotoxin (i.e., it is a superantigen) ❖ Superantigens are potent, can cause range of outcomes, including: Fever, Shock, Death, Inflammation, Cytotoxicity, Deletion of T-cells, and Autoimmunity ❖ Superantigens are predominantly bacterial in origin, and include staphylococcal enterotoxin and toxin-1, which is responsible for toxic shock syndrome 28  Clinical Findings There are Two Syndromes: (1) One syndrome has short incubation period (4 hours) and consists primarily of nausea and vomiting, similar to staphylococcal food poisoning (2) The other has a long incubation period (18 hours) and features watery, non- bloody diarrhea, resembling clostridial gastroenteritis 29 Laboratory Diagnosis This is not usually done 30 Treatment Only symptomatic treatment is given 31 Prevention There is no specific means of prevention Rice should not be kept warm for long periods 32 33