Bacillus and Similar Organisms

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Bacillus and Similar Organisms

General Characteristics

Bacillus species previously were phenotypically classified. With the development of rapid nucleic acid sequencing, the genus has been reorganized based on 16srRNA sequence analysis. The group now contains 53 genera. Bacillus remains the largest genus within this group and contains the most important medically relevant organisms. Bacillus spp. and related genera Brevibacillus and Paenibacillus are aerobic and facultative anaerobic, gram-positive, spore-forming rods. Only the species most commonly associated with human infections are discussed.

Bacillus Anthracis

Clinical microbiologists are sentinels for recognition of a bioterrorist event, especially involving microorganisms such as B. anthracis. Even though this organism is rarely found, sentinel laboratory protocols require ruling out the possibility of anthrax before reporting any blood, CSF, or wound cultures in which a large gram-positive aerobic rod is isolated. During the 2001 terrorist attacks on the United States, the index case associated with the anthrax distribution was discovered by an astute clinical microbiologist who identified large gram-positive rods in a patient’s cerebrospinal fluid. B. anthracis should be suspected if typical nonhemolytic “Medusa head” or ground glass colonies are observed on 5% sheep blood agar. The Red Line Alert Test (Tetracore, Inc., Gaithersburg, Maryland) is a Food and Drug Administration (FDA)-cleared immunochromatographic test that presumptively identifies B. anthracis from blood agar (Figure 16-1). The sentinel laboratory anthrax protocol was revised in 2005 and again in 2010 to use FDA-cleared tests in order to rule out nonhemolytic, nonmotile Bacillus spp. as potential isolates of B. anthracis.

Epidemiology

Anthrax remains the most widely recognized bacillus in clinical microbiology laboratories. It is primarily a disease of wild and domestic animals including sheep, goats, horses, and cattle. The decline in animal and human infections is a result of the development of veterinary and human vaccines as well as improvements in industrial applications for handing and importing animal products. The organism is normally found in the soil and primarily causes disease in herbivores. Humans acquire infections when inoculated with the spores, either by traumatic introduction, ingestion, or inhalation during exposure to contaminated animal products, such as hides (Table 16-1). Bacillus anthracis produces endospores, which are highly resistant to heat and desiccation. The spores remain viable in a dormant state until they are deposited in a suitable environment for growth, including moisture, temperature, oxygenation, and nutrient availability. Because of the ability to survive harsh environments, infectiousness, ease of aerosol dissemination, and high mortality rate, the spores may be effectively used as an agent of biologic warfare (see Chapter 80 for additional information).

TABLE 16-1

Epidemiology

Species Habitat (Reservoir) Mode of Transmission
Bacillus anthracis Soil: contracted by various herbivores Direct contact: animal tissue or products such as wool or hair (infecting organisms)
Trauma or insect bites: organisms or spores
Inhalation: spores; Woolsorters’ disease
Ingestion: contaminated meat
Person-to-person transmission has not been documented
Bacillus cereus, Bacillus circulans, Bacillus licheniformis, Bacillus subtilis, other Bacillus spp., Brevibacillus sp., and Paenibacillus spp. Vegetative cells and spores ubiquitous in nature; may transiently colonize skin or the gastrointestinal or respiratory tracts Trauma
Associated with immunocompromised patients
Ingestion of food (rice) contaminated with B. cereus or toxins formed by this organism

Pathogenesis and Spectrum of Disease

B. anthracis is the most highly virulent species for humans and is the causative agent of anthrax. The three forms of disease are cutaneous, gastrointestinal (ingestion), and pulmonary (inhalation) or woolsorters’ disease (Table 16-2). The cutaneous form accounts for most human infections and is associated with contact with infected animal products. Infection results from close contact and inoculation of endospores through a break in the skin. Following inoculation and incubation period of approximately 2 to 6 days in most cases, a small papule appears that progresses to a ring of vesicles. The vesicles then develop into an ulceration. The typical presentation is of a black, necrotic lesion known as an eschar. The mortality rate for untreated cutaneous anthrax is low, approximately 1%.

TABLE 16-2

Pathogenesis and Spectrum of Disease

Species Virulence Factors Spectrum of Diseases and Infections
Bacillus anthracis Capsule exotoxins (edema toxin and lethal toxin) swelling and tissue death Causative agent of anthrax, of which there are three forms:
Cutaneous anthrax occurs at site of spore penetration 2 to 5 days after exposure and is manifested by progressive stages from an erythematous papule to ulceration and finally to formation of a black scar (i.e., eschar); may progress to toxemia and death
Pulmonary anthrax, also known as woolsorters’ disease, follows inhalation of spores and progresses from malaise with mild fever and nonproductive cough to respiratory distress, massive chest edema, cyanosis, and death
Gastrointestinal anthrax may follow ingestion of spores and affects either the oropharyngeal or the abdominal area; most patients die from toxemia and overwhelming sepsis
Bacillus cereus Enterotoxins and pyogenic toxin Food poisoning of two types: diarrheal type, characterized by abdominal pain and watery diarrhea, and emetic type, which is manifested by profuse vomiting; B. cereus is the most commonly encountered species of Bacillus in opportunistic infections including posttraumatic eye infections, endocarditis, and bacteremia; infections of other sites are rare and usually involve intravenous drug abusers or immunocompromised patients
Bacillus circulans, Bacillus licheniformis, Bacillus subtilis, other Bacillus spp., Brevibacillus sp., and Paenibacillus spp. Virulence factors unknown Food poisoning has been associated with some species but is uncommon; these organisms may also be involved in opportunistic infections similar to those described for B. cereus

Ingestion anthrax results from ingestion of spores and is presented in two forms: oral or oropharyngeal with the lesion in the buccal cavity, on the tongue, tonsils, or pharyngeal mucosa and gastrointestinal anthrax with the lesions developing anywhere in the gastrointestinal tract. Oropharyngeal symptoms may include sore throat, lymphadenopathy, and edema of the throat and chest. The initial symptoms on gastrointestinal anthrax may be nonspecific with progression to abdominal pain, bloody diarrhea, and hematemesis. The mortality rate is much higher than that of cutaneous anthrax and usually attributed to toxemia and sepsis.

Pulmonary (inhalation) anthrax is due to inhalation of the spores. The endospores are ingested by macrophages and taken to the lymph nodes where the infection develops into a systemic infection. The disease develops from flulike symptoms to respiratory distress, edema, cyanosis, shock, and death. Patients typically demonstrate abnormal chest x-rays with pleural effusion, infiltrates, and mediastinal widening. Woolsorters’ disease and ragpickers’ disease are used to describe respiratory infections that result from exposure to endospores during the handling of animal hides, hair, or fibers and other animal products.

Complications often follow all three forms of anthrax disease. Patients often develop meningitis within 6 days after exposure. Recovery results in long-term immunity to subsequent infections.

Virulence is attributed to the production of anthrax toxin. The toxin consists of three proteins. One of these proteins, protective antigen (PA), facilitates the transport of the other two proteins into the cell. Edema factor, EF, is responsible for edema, whereas lethal factor, LF, is primarily responsible for death.

Bacillus Cereus

B. cereus is another clinically relevant species worthy of identification. It is penicillin resistant, beta-hemolytic, and motile, and it produces a wide zone of lecithinase on egg yolk agar (Figure 16-2).

Pathogenesis and Spectrum of Disease

B. cereus “food poisoning” is associated with the ingestion of a wide variety of foods including meats, vegetables, deserts, sauces, and milk. A higher incidence is seen following the ingestion of rice dishes. Following ingestion patients present with one of two types of symptoms: diarrhea and abdominal pain within 8 to 16 hours or nausea and vomiting within 1 to 5 hours. B. cereus produces several toxins implicated in the diarrheal symptoms, including hemolysin BL (Hbl), nonhemolytic enterotoxin (Nhe), and cytotoxin K (CytK). The three toxins are believed to act synergistically, with Nhe responsible for the major symptoms in the diarrheal presentation of the infection. The emetic form of illness is associated with a heat-stable, proteolysis, and acid resistant toxin, cereulide, produced in food.

In addition to the food poisoning associated with B. cereus, it is a serious pathogen of the eye, causing progressive endophthalmitis. Identification of B. cereus from a patient’s eye can cause permanent damage and should be reported to the physician immediately.

Bacillus Subtilis, Brevibacillus Sp., and Paenibacillus Spp.

B. subtilis has been identified in clinical specimens in a variety of cases including pneumonia, bacteremia, septicemia, surgical wounds, meningitis following head trauma, and other surgical infections. Rare human infections have been associated with a variety of Bacillus spp., including B. clausii, B. licheniformis, B. circulans, B. coagulans, B. pumilus, Paenibacillus polymyxa, and Brevibacillus sp. Many of these organisms are common environmental contaminants. Identification of these organisms is not recommended unless isolated from a sterile site (e.g., blood) or found in large numbers in pure culture. Therefore, identification and interpretation should be closely evaluated in conjunction with the patient’s signs and symptoms and consultation with the attending physician.