Lect 3-4 Bacteriology PDF

Mycobacterium tuberculosis Lect. 3 Mycobacterium species are a group of acid-fast, aerobic, slow- growing bacteria. The genus comprises more than 70 different species, of which about 30 have been associated with human disease The most important species is Mycobacterium tub...

Mycobacterium tuberculosis Lect. 3 Mycobacterium species are a group of acid-fast, aerobic, slow- growing bacteria. The genus comprises more than 70 different species, of which about 30 have been associated with human disease The most important species is Mycobacterium tuberculosis, the causative agent of tuberculosis. Tuberculosis is a chronic, progressive mycobacterial infection, often with an asymptomatic latent period following initial inf ection. Tuberculosis most commonly affects the lungs. Symptoms include productive cough, fever, weight loss, and malaise. Diagnosis is most often by sputum smear and culture and, when available, by nucleic acid amplification tests. Treatment is with multip le antimicrobial drugs given for at least 4 months Mycobacterium tuberculosis is a weakly gram-positive, non-motile, rod-shaped bacterium. It is also a facultative intracellular parasite as well as an obligated aerobic. This explains why tuberculosis is a disease typically affects the lungs. Unlike other bacteria that have cell walls mainly composed of peptidoglycan, the major cell wall component of mycobacterium is lipids. The lipid layer makes it impervious for gram staining, and it shows either gram-positive or gram-negative. More advance methods like acid- fast staining applied to detect the function of Mycobacterium. Mycobacterium tuberculosis has a low generation time; cell division occurs every 18-24 hours, which is extremely slow compared with other bacteria that normally has a division rate every 20 minutes. The reason is that the mycolic acid has a low permeability which can protects bacterium taking damage from the immune system such as phagosome and macrophage. However, the impervious characteristic also limits nutrient accessibility, decreasing the rate of diffusion and eventually leads to a slower growth rate.  Symptoms of active TB include:  Coughing that lasts three or more weeks  Coughing up blood  Chest pain, or pain with breathing or coughing  Unintentional weight loss  Fatigue  Fever  Night sweats  Chills and Loss of appetite  Antibiotics used to treat TB are usually isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) and ethambutol (EMB) or streptomycin (SM). These are used in combination to prevent development of antibiotic resistance, which is of particular concern in M. tuberculosis.  It can be difficult to keep patients compliant with treatment. o Because of the slow growth of M. tuberculosis the treatment course is very long (6-9 months) o The side effects of these antibiotics can be unpleasant o Patients are often asymptomatic when they begin treatment o Public health officials sometimes use directly observed therapy (DOT) to ensure compliance   Many strains of M. tuberculosis are now resistant to multiple drugs (MDR-TB). Some are resistant to most of the first- and second-line antibiotics (XDR-TB)  There is a vaccine available (the BCG vaccine), but it is not particularly effective and is not used in the United States Primarily Virulence Factors  Mycobacterium tuberculosis does not produce any toxins or exoenzymes which damage tissue  The protective waxes in the cell wall which prevent destruction by the immune system are the primary virulence factor of M. tuberculosis  The damage caused in the course of tuberculosis is a result of the immune response to M. tuberculosis M. Tuberculosis might also hear about systemic miliary tuberculosis, which can spread throughout your body and cause:  Meningitis, an inflammation of your brain.  Sterile pyuria, or high levels of white blood cells in your urine.  Pott’s disease, also called spinal tuberculosis or tuberculosis spondylitis.  Addison’s disease, an adrenal gland condition.  Hepatitis, a liver infection.  Lymphadenitis in your neck, also called scrofula or TB lymphadenitis  Acid-fast bacillus (AFB) is a type of bacteria that causes tuberculosis and other types of mycobacterial infections, such as leprosy (Hansen's disease) Mycobacterium leprae Leprosy is caused by Mycobacterium leprae (M. leprae) and M. lepromatosis, an obligate intracellular organism, and over 200,000 new cases occur every year. M. leprae parasitizes histiocytes (skin macrophages) and Schwann cells in the peripheral nerves. Although leprosy can be treated by multidrug therapy, some patients relapse or have a prolonged clinical course and/or experience leprosy reaction. These varying outcomes depend on host factors such as immune responses against bacterial components that determine a range of symptoms. Corynebacterium diphtheria Lect.4 Corynebacterium diphtheriae infects the nasopharynx or skin. Toxigenic strains secrete a potent exotoxin which may cause diphtheria. The symptoms of diphtheria include pharyngitis, fever, swelling of the neck or area surrounding the skin lesion. Diphtheritic lesions are covered by a pseudomembrane. The toxin is distributed to distant organs by the circulatory system and may cause paralysis and congestive heart failure. Corynebacterium diphtheriae is a nonmotile, noncapsulated, club- shaped, Gram-positive bacillus. Toxigenic strains are lysogenic for one of a family of corynebacteriophages that carry the structural gene for diphtheria toxin, tox. Corynebacterium diphtheriae is classified into biotypes (mitis, intermedius, and gravis) according to colony morphology, as well as into lysotypes based upon corynebacteriophage sensitivity. Most strains require nicotinic and pantothenic acids for growth; some also require thiamine, biotin, or pimelic acid. For optimal production of diphtheria toxin, the medium should be supplemented with amino acids and must be deferrated. Pathogenesis Asymptomatic nasopharyngeal carriage is common in regions where diphtheria is endemic. In susceptible individuals, toxigenic strains cause disease by multiplying and secreting diphtheria toxin in either nasopharyngeal or skin lesions. The diphtheritic lesion is often covered by a pseudomembrane composed of fibrin, bacteria, and inflammatory cells. Diphtheria toxin can be proteolytically cleaved into two fragments: an N-terminal fragment A (catalytic domain), and fragment B (transmembrane and receptor binding domains). Fragment A catalyzes the NAD+-dependent ADP-ribosylation of elongation factor 2, thereby inhibiting protein synthesis in eukaryotic cells. Fragment B binds to the cell surface receptor and facilitates the delivery of fragment A to the cytosol. Host Defenses Protective immunity involves an antibody response to diphtheria toxin following clinical disease or to diphtheria toxoid (formaldehyde-inactivated toxin) following immunization. Diagnosis Clinical diagnosis depends upon culture-proven toxigenic C diphtheriae infection of the skin, nose, or throat combined with clinical signs of nasopharyngeal diphtheria (e.g., sore throat, dysphagia, bloody nasal discharge, pseudomembrane). Toxigenicity is identified by a variety of in vitro (e.g., gel immunodiffusion, tissue culture) or in vivo (e.g., rabbit skin test, guinea pig challenge) methods. Role Of Biomarkers A rise in biomarkers, such as total leukocyte count and serum glutamic oxalo-acetic transaminase levels (SGOT), can be associated with a worse prognosis and can correlate with disease severity. Similarly, CPK MB and cardiac troponin can be used to predict disease activity.  Corynebacterium diphtheria has many similarities with other disease conditions. Following are very close mimick to Crynobacterium diphtheria:  Viral pharyngitis  Streptococcal pharyngitis  Acute epiglottitis  Infectious mononucleosis  Oral candidiasis  Infective endocarditis  Angioedema  Epiglottitis  Retropharyngeal abscess Risk factors People who are at increased risk of catching diphtheria include:  Children and adults who don't have up-to-date vaccinations  People living in crowded or unsanitary conditions  Anyone who travels to an area where diphtheria infections are more common  Antibiotics, such as penicillin or erythromycin, help kill bacteria in the body, clearing up infections. Antibiotics lessen the time that someone with diphtheria is contagious. An antitoxin. If a doctor suspects diphtheria, he or she will request a medication that counteracts the diphtheria toxin in the body.  Control Immunization with diphtheria toxoid is extraordinarily effective. Diphtheria patients must be promptly treated with antitoxin to neutralize circulating diphtheria toxin.