Lecture 12: Corynebacterium and Mycobacterium
For Corynebacterium species, we discussed the organism Corynebacterium diphtheria. Corynebacterium diphtheria’s characteristics
∙ Gram-positive, club-shaped organism
∙ Non-motile and can be aerobic or facultative anaerobic
∙ Contains metachromatic granules; staining with methylene blue stains the metachromatic granules red and the rest of the cell blue. This allows for the detection of these granules. ∙ Includes short mycolic acids in its cell wall
∙ Are present plentifully to plants and animals
∙ It commonly colonizes the skin, upper respiratory tract, gastrointestinal tract, and urogenital tract of humans
Corynebacterium diphtheria’s Pathogenesis
∙ It’s only natural host are humans, and are transmitted by respiratory droplets or skin contact. ∙ It is rarely found in the U.S.
∙ Although it is primarily a pediatric disease, it has shifted to older age groups in vaccinated areas ∙ It’s most common virulence factor is an A-B subunit exotoxin called Diphtheria toxin (can be easily remembered since its name is including in the organism associated with it. Below is a short summary of how it works:
1. The B subunit (B stands for binding) binds onto a receptor commonly found on nerve, heart, and oropharyngeal cells, heparin-binding epidermal growth factor.
2. After binding, the A subunit (A stands for active) moves into the cytosol of the cell. 3. ADP-ribosylates elongation factor-2 (EF-2), which is involved with translation. Since there is only one EF-2 per cell, this inhibits protein synthesis and causes cell death. If you want to learn more check out What does an archeologist study?
Corynebacterium diphtheria’s Symptoms, Prevention, and Treatment
∙ It develops after a 2 to 4-day incubation period
∙ Includes malaise, exudative pharyngitis, and low-grade fever
∙ Pseudomembrane (dirty white-grayish covering) can be seen covering much of the pharynx ∙ Systemic complications can arise such as myocarditis, which can lead to cardiac arrhythmia and death; Neurotoxicity can lead to peripheral neuritis
∙ Treatment with penicillin or erythromycin, as well as administration of diphtheria antitoxin ∙ Immunization with diphtheria toxoid can preventing symptomatic disease; commonly apart of the DPT vaccine, a series of 5 shots at ages 2, 4, 6, 15 to 18 months, and at 4 to 6 years ∙ The toxoid booster, in combination with tetanus toxoid, is recommended to be given every 10 years
For Mycobacterium species, we discussed Mycobacterium tuberculosis, Mycobacterium leprae, Mycobacterium avium, and Mycobacterium ulcerans If you want to learn more check out What is the greek concept of arete?
Mycobacterium species’ characteristics
∙ It is non-spore forming and an aerobic rod
∙ Has very slow growing due to complex cell wall and fastidious nature. If you want to learn more check out What is the meaning of a wash fixture?
∙ Its cell wall contains:
o Hydrophobic property, allowing in to refract many stains and disinfectants
o Mycolic acids, allowing it to be acid-fast
o Lipoarabinomannan (LAM)
o Many lipids, including glycolipids and phospholipids
o Transport proteins and porins.
o Cord factor, allowing the bacteria to grow in parallel serpentine rows (important virulence factor)
About Mycobacterium tuberculosis
∙ Its only natural reservoir is humans (infected appropriately one-third of the total population), spreading by person-to-person contact We also discuss several other topics like What rna is the most abundant in the cell?
∙ Also can be caused by inhaling infectious aerosols
∙ An infection can easily occur if tubercle bacilli, even a small amount, moves to the alveoli ∙ 9,000,000 new cases and 2 million deaths occur annually by this organism We also discuss several other topics like What are the types of mollusks?
∙ In U.S. incidence has decreased over the years—*this is an important note
∙ Majority of the U.S. cases are caused by immigrants traveling into the country ∙ High risk groups for Mycobacterium tuberculosis include:
o Drug and alcohol abusers
o People with HIV
Mycobacterium tuberculosis’s Pathogenesis
∙ It does not express any toxins
∙ However, it is an intracellular pathogen, preventing the phagosome-lysosome combination. This is due to an export repetitive protein (ERP)
∙ Macrophages secrete IL-12 and TNF-α during the infection, increasing the amount of phagolysosome fusion attempts
∙ Also, TNF-α stimulates the release of nitric oxide to further increase intracellular killing ∙ Different types of lesions can be included: Don't forget about the age old question of What are the interactions between cells and their environment?
∙ Exudative lesion – occurring at the site of infection, it is an acute inflammatory response in the lungs
∙ Granulomatous lesion– includes macrophages, epithelioid cells, giant cells, CD8 and CD4 T cells
a. Called a granuloma or tubercle
b. Heals by fibrosis and calcification, walling off the infection to allow the bacterium to survive
c. Bacteria can remain in the latent phase for long periods of time. Although
reactivation mostly never occur in individuals, reactivate can happen from old age or immunosuppression
∙ Organisms are spread by:
o Person-to-person, with the erosion of tubercle occurring in the lungs
o It can enter into the bloodstream if the immune system fails to completely fight the infection or if the person is immunocompromised
PPD (purified protein derivatives) skin test can detect Mycobacterium tuberculosis-- delayed hypersensitivity reaction--(type 4)
How the test works:
a. The test measures the induration (thickening) of the skin surrounding the test site b. Induration measuring 15mm or more is positive in people with no known risk factors, 10 mm or more is positive for high risk people, and 5mm or more is positive for a person who has been in contact with another with active TB.
Mycobacterium tuberculosis’s disease symptoms and diagnosis
o Symptoms include fever, fatigue, night sweats, weight loss; if TB is found in the upper lobes of the lungs, a cough and hemoptysis with tissue destruction can occur
o Pulmonary TB is diagnosed by X-rays, a positive PPD test, and laboratory detection of the organism Mycobacteria
o Extrapulmonary TB (miliary) – examples are Tuberculosis meningitis and tuberculosis osteomyelitis
o due to a hematogenous spread during the initial replication
o Lesions resemble millet seeds (seeds from the Wild West)
Mycobacterium tuberculosis’s treatment
o Rifampin and isonicotinic acid hydrazide (isoniazid, INH) are given together to be very effective. *to help remember, Mycobacterium tuberculosis has an “ri” combination in its name* These drugs will quickly make the patient non-contagious.
o This bacterium as a tendency to easily become resistant to antibiotics. The chance of resistance developing when two drugs are given in combination is slow and why it is more effective
o New strains of resistant TB called extensively drug resistant (XDR) TB have emerged and are resistant to rifampin, INH, fluoroquinolones and at least one of the second line of drugs (kanamycin, amikacin, capreomycin)--exactly from the notes
Mycobacterium Leprae’s characteristics
o Causes leprosy or Hansen disease
o Weakly gram positive, and a strong acid-fast rod (all Mycobacterium species are acid-fast rods) o Also very slow growing; prolonged incubation period- symptoms can develop 20 years after infection
o Cannot be grown in culture, is growth on armadillo’s feet
o Humans are natural hosts, however, armadillos may serve as its source
o Can be found on the skin and superficial nerves
o Only about 100 new cases in U.S. annually; 300,000 worldwide with most in India, Nepal, and Brazil
Mycobacterium Leprae’s Pathogensis
o Organism replicates inside of skin histiocytes, endothelial cells, and Schwann cells of nerves o Two main forms:
o Tuberculoid leprosy – it limits growth in cell mediated response, granulomas form containing giant cells, and indicates a positive result on a lepromin skin test. Hypo pigmented macular skin lesions, thickened superficial nerves, and significant anesthesia in the skin are seen with this disease
o Lepromatous leprosy – poor cell mediated response, skin and mucous membrane lesions contain numerous organisms, includes foamy (full of lipids) histiocytes, and a negative result is found on the lepromin skin test. Multiple nodular skin lesions are seen with this disease. Patients often start to develop erythema nodosum leprosum (ENL) after therapy. It means the cell-mediated immunity is returning back to normal
Mycobacterium Leprae’s Treatment
o Also, uses a combination of drugs, such as dapsone, rifampin, and clofazimine. o An issue with the drugs is that they worked so well, they can have antigens released from destroyed organisms that can produce an inflammation
o Therapy requires a minimum of 2 years, and sometimes life-long.
Mycobacterium avium’s About and Treatment
o M. avium and M. hominissuis – can cause disease in immunosuppressed people (an extreme problem for HIV patients and smokers)
o 3 forms of the disease can present (exactly from notes):
o Middle-age or older men with history of smoking and underlying pulmonary disease, developing a cavitary disease that resembles tuberculosis on X-rays
o Elderly female non-smokers – develop middle lobe infiltrates with a patchy nodular appearance and associated bronchitis (Lady Windermere syndrome)
o Formation of a solitary pulmonary nodule
∙ **Patients with AIDS – MAC in these patients is disseminated with no organ spared; tissues of patients are literally filled with mycobacteria; usually in terminal stages
--Treatment for this bacterium uses clarithromycin or azithromycin combined with ethambutol and rifabutin
Since there was little information in the slides about Mycobacterium ulcerans, I only included notes Dr. Jordan said related to the pictures shown
o Buruli ulcer prevalence in 33 countries, highest in west-africa
o Mycolactone: Major Virulence Determinant—it immunosuppresses
o Associated with aquatic environments
o Questions, such as Reservoir, Replication, Transmission, and Niche/matrices associations, are still being answered
Its treatment includes an 8-week antibiotic combination, using one of the following combinations:
o A combination of rifampicin and streptomycin
o A combination of rifampicin and clarithromycin in pregnant women.
o A combination of rifampicin and moxifloxacin