أ.د. عالية عبد الباقي شعيب المملكة العربية السعودية جامعة الملك سعود كلية العلوم قسم البنات والأحياء الدقيقة Mic 522 Toxins in Pathogenic Bacteria Corynbacterium

Inhibitors of Protein Synthesis: A. Diphtheria Toxin of Corynebacterium diphtheriae. Diphtheria toxin is phage encoded. The gene for the toxin, tox, resides on a lysogenic phage (B phage). All phage isolates encode the same toxin, but not all strains carry the phage.

Only strains with the toxin gene can cause disease. In the U.S., most isolates of Corynebacterium diphtheriae do not produce toxin. However, strains lysogenic for the toxin phage are still found in the developing world, as are cases of diphtheria. The organism infects the throat, or occasionally skin wounds.

The toxin is produced in response to iron restriction. (Like Exotoxin A of Pseudomonas aeruginosa.) As you recall from the Bacterial Physiology section, the host is able to restrict iron on mucosal surfaces and in tissues through the production of iron-binding proteins like lactoferrin and transferrin.

Under these conditions, C. diphtheriae turns on toxin synthesis, leading to tissue destruction and the increased availability of nutrients, including iron.

The Mechanism of Action of Diphtheria Toxin Diphtheria toxin is synthesized as a single 560 amino acid chain, which must be cleaved into two chains to work. A is active chain, B mediates entry. The structure of diphtheria toxin can be seen by important links.structure of diphtheria toxin

Diphtheria toxin catalyzes the ADP ribosylation of EF2, knocking out host protein synthesis. (Like Exotoxin A of Pseudomonas aeruginosa.) Clinically, necrosis of the posterior pharynx is seen. As the toxin is absorbed systemically, it produces heart toxicity that presents as cardiac failure.

Non-toxin producing strains can also colonize the pharynx. There is a vaccine to prevent the disease. Also, if a patient recovers from natural disease, they are immune. Diphtheria: Images of Diptheria WHO fact sheet on diphtheria In a Nutshell from the CDC