toxigenic bacteria Flashcards
compare Corynebacterium diphtheriae and Bordetella pertussis
In both cases, the primary site of infection is the upper respiratory tract, but the major manifestations of the infections are the result of the production of potent exotoxins that have similar enzymatic mechanisms of action at the molecular level. These toxins are components of extremely important vaccines.
Lab Diagnosis of C. diphtheria
Requires demonstration of toxin production by the isolate. Immunoprecipitation and PCR detection of tox gene. Cultures are obtained from the throat and/or any skin lesions in the case of cutaneous diphtheria. Can take at least 5 days
Corynebacterium structure
pleomorphic (occurring in various distinct forms), gram-positive bacilli. often appear as rods clubbed at one or both ends.
Clinical diagnosis of C. diphtheria
diagnosis is usually made on clinical grounds. Treatment (antitoxin and antibiotics) is administered before a final laboratory diagnosis is made bcause antibodies cannot reverse the effects of the toxin once it is bound to the eukaryotic cell receptor of the toxin, so the sooner the unbound toxin is neutralized the less likely it is to cause damage.
which form of diphtheria is more contagious
cutaneous form
B. pertussis structure
Gram-negative coccobacillus grows very slowly (small colonies in 3-5 days)
B. pertussis diagnosis
A nasopharyngeal (NP) aspirate (saline flush) or a nasopharyngeal swab is collected. The organism is most frequently recovered in the catarrhal or very early paroxysmal stages. The organism is extremely difficult to recover past the catarrhal stage. Culture is the Gold standard (100% specificity)- tkes 3-4 days. NO testing for toxin. Presently, a PCR based test is increasingly being used for diagnosis
During what time is pertussis best diagnosed
PCR should be tested from NP specimens taken at 0-3 weeks following cough onset, but may provide accurate results for up to 4 weeks of cough in infants or unvaccinated persons. After the fourth week of cough, the amount of bacterial DNA rapidly diminishes, which increases the risk of obtaining false-negative results.
Diphtheria toxin MOA
Cleaved by trypsin-like enzymes > releases active fragment A > Fragment B and hydrophobic domain help deliver fragment A to epidermal growth factor precursor then cytoplasm > Fragment A ADP-ribosylates Elongation factor-2 (EF-2) >EF-2 cant function in chain elongation so protein synthesis stops. Targt cells die (cardiac), kidney and peripheral nerves are damaged, heart stops
Pertussis toxin MOA
The A toxin ADP-ribosylates the inhibitory subunit of adenylyl cyclase of eukaryotic cell > adenylyl cyclase is turned on > increased cAMP. Pertussis toxin does NOT kill cell like diphtheria, but the full MOA is unknown
virulence factors for diphtheria
diphtheria toxin is only virulence factor
virulence factors for pertussis
- pertussis toxin. 2. tracheal cytotoxin- part of the peptidoglycan, destroys ciliated epithelial cells in upper respiratory tract. 3. Adenylyl cylase toxin- affects macrophage trafficking. 4. Filametous hemagglutinin (FHA)- attachment to ciliated respiratory epithelial cells
regulation of diphteria toxin
regulated by iron. , increased amounts of iron in the environment (>10µM) will shut off toxin synthesis while <1µM will lead to increased expression. a dead eukaryotic cell gives up its iron more readily than a live cell, which is required for bacterial growth. Also requires tox gene from bacteriophage
regulation of pertussis toxin
VIR gene regulates most of the pertussis virulence factors.
Diphtheria manifestations
membranous nasopharyngitis and/or obstructive laryngotracheitis plus low-grade fever and gradual onset of manifestation during 1 to 2 days. Bull neck. Cutaneous diphtheria common in temperate climates. Toxin production affects heart, peripheral nerves and kidneys.
