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Outline

CORYNEBACTERIUM MYCOBACTERIUM

INTRODUCTION Corynebacterium & Mycobacterium Gram-positive Non-spore-forming Pleomorphic rods

Corynebacterium Gram-positive Club-shaped rods Aerobic to facultatively anaerobic 0.3 - 0.8 mm wide by 1 to 8 mm long

"The major pathogen in the..." The major pathogen in the genus = C. diphtheriae - the etiologic agent of diphtheria We use the term "diphtheroid" for all other Gram-positive rods resembling C. diphtheriae; i.e., Gram-positive, club-shaped rods

Corynebacterium diphtheriae

Corynebacterium diphtheriae

C. diphtheriae Obligate aerobe No flagella No capsule

Exotoxin C. diphtheriae produces an exotoxin responsible for the disease Diphtheria The toxin attaches to cells and blocks their protein synthesis They die within a few hours

"Only bacterial cells that are..." Only bacterial cells that are infected with a specific prophage contain the gene responsible for toxin production All other cells are avirulent

"When the bacterium has sufficient..." When the bacterium has sufficient iron, no toxin is produced because iron molecules reside on gene repressors that keep the gene from acting

"When the immune system responds..." When the immune system responds to infection by sequestering iron, it causes the metal ions to pop off the gene repressors, thus allowing the gene to be expressed The rush of toxin kills nearby cells releasing nutrients, including iron

"This toxin also directly damages..." This toxin also directly damages the heart and nervous system

"C." C. diphtheria is transmitted either by droplet infection from asymptomatic carriers and active cases or by contact with cutaneous lesions Human disease usually begins as an upper respiratory tract infection with the toxin causing cellular necrosis

"This results in the accumulation..." This results in the accumulation at the site of infection of dead epithelial cells, C. diphtheriae cells, fibrin, erythrocytes and leukocytes This forms a characteristic grayish pseudomembrane

Immunity The toxin is very immunogenic The DTP vaccine used to immunize against diphtheria is called DTP The D stands for diphtheria The T and P stand for Tetanus and Pertussis The vaccine uses a formalin denatured toxin

Treatment Because diphtheria toxin can act rapidly, suspected cases are treated immediately with antitoxin The infection itself can then be treated with antibiotics Penicillin, erythromycin, and tetracycline are all effective

Corynebacterium matruchotii

Corynebacterium matruchotii

Corynebacterium matruchotii Filamentous Gram-positive Facultative anaerobe Implicated in calculus formation

"It is also found as..." It is also found as the central core of “corn cobs”, which have a central rod and surrounding S. sanguis cells

Corn cobs

"Corynebacterium matruchotii was previously classified..." Corynebacterium matruchotii was previously classified as Bacterionema matruchotii

MYCOBACTERIUM

Cultural Characteristics Rods 0.2 to 0.6 mm wide, 1 to 10 mm long Sometimes filaments Sometimes branching rods Sometimes the cells are almost coccal No spores

"They are said to be..." They are said to be acid-fast, a specific staining characteristic (see table below)

Acid-Fast Staining Procedure Reagents Mycobacterium Other Ziehl-Neelsen stain Red Red Acid Alcohol 1 Red Clear Methylene Blue 2 Red Blue 1 Decolorizer 2 Counterstain

"The mycobacteria are also slow..." The mycobacteria are also slow growing, taking between 1 and 6 weeks to grow out on appropriate media

Species Mycobacterium pathogens: Mycobacterium tuberculosis, the cause of tuberculosis Mycobacterium leprae, the cause of leprosy Other species implicated in infections in immunosuppressed individuals

Mycobacterium tuberculosis

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Tuberculosis-the disease Tuberculosis is usually a lung disease There is an initial infection with M. tuberculosis

"The disease," The disease, tuberculosis, may occur within weeks of infection Normally, the body fights this off but doesn’t kill all the organisms They remain dormant in the lung The patient is said to have a latent tubercular infection

"Later in life," Later in life, usually decades later, if the immune systems weaken due to Normal aging Disease, such as AIDS Immunosuppression following a transplant or cancer therapy Prolonged anti-inflammatory therapy The organisms can come out of dormancy and cause the disease - Tuberculosis

Discovery and Koch's Postulates M. tuberculosis was discovered by Robert Koch It led to the development of Koch's postulates, which are: To establish an organism as the etiologic agent of a disease you must do the following

Koch's Postulates 1. Observe the organism in every case of the disease 2. Grow the organism in pure culture in the laboratory 3. Get the disease when you reintroduce the organism into a susceptible animal 4. Observe the organism in and isolate it from the new animal

Method of Spread TB is usually a lung infection

Method of Spread It is generally spread by droplets, usually when the patient coughs

Virulence Factors Virulent strains of M. tuberculosis produce a substance called cord factor When cells are stained, they may be clumped together in long serpentine cords The substance responsible for this has been isolated and found to be toxic

Diagnosis Tuberculosis can be diagnosed by several methods 1. Demonstration of acid-fast bacilli (AFB) in smears made from sputum samples 2. M. tuberculosis can be cultured from sputum

"3." 3. The development of a positive skin test to a purified material from the culture medium that the M. tuberculosis has grown in This material is called Purified Protein Derivative or PPD and the test is called the Mantoux Test

"In the Mantoux Test," In the Mantoux Test, 0.1 ml of diluted PPD is injected into the skin of the forearm

"If a person has been..." If a person has been exposed to M. tuberculosis and develops the delayed hypersensitivity (Type IV) that is characteristic of tuberculosis, then they will develop an area of swelling and erythema at the site of injection 48 hours later

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"This only means that they..." This only means that they have been infected with M. tuberculosis It does not mean they have the disease tuberculosis

Treatment Tuberculosis has traditionally been treated with a combination of 2 or more antibiotics for a period of up to 1 year

"Up until the last decade..." Up until the last decade this worked fine We are now seeing multiply drug resistant strains of TB, called MDRTB

"In some cases," In some cases, none of the antibiotics we have work very well This situation was probably brought about by inadequate treatment; i.e., patients not taking the antibiotics for the full period

"It is important to note..." It is important to note that if someone has been diagnosed as having tuberculosis, they are considered infectious until a sputum smear shows no acid-fast bacilli (AFB)

Mycobacterium leprae

"This organism," This organism, the cause of leprosy, has never been cultured Leprosy can be found in the United States - mostly in the southern states

Leprosy

Other Mycobacteria

"A number of other mycobacterial..." A number of other mycobacterial infections have increasingly been seen in people that are immunosuppressed, most often in AIDS patients

"These organisms are often referred..." These organisms are often referred to as opportunistic pathogens, because they are of low virulence and don’t normally cause disease in a healthy person but, if the person's immunity is lowered, they seize the opportunity and cause an infection

"One group of organisms responsible..." One group of organisms responsible for many of these infections is the M. avium complex (M. avium and M. intracellulare) M. avium complex is sometimes abbreviated MAC