Introduction
Corynebacterium diphtheriae, or C. diphtheriae, derives its name from the Greek terms "Coryne," meaning club, and "diphtheriae," signifying leather. Hence, C. diphtheriae is a club-shaped bacterium responsible for diphtheria, characterized by the development of a tough, leathery membrane in the pharynx. This bacterium encompasses four primary subspecies: C. diphtheriae mitis, C. diphtheriae Intermedius, C. diphtheriae Gravis, and C. diphtheriae Belfanti.
Bacterium Characteristics
C. diphtheriae possesses a thick peptidoglycan cell wall, exhibiting purple staining in Gram staining, classifying it as a gram-positive bacterium. It thrives aerobically, necessitating oxygen for its growth, and lacks the ability to form spores. When subjected to Albert's stain, these bacteria display distinctive characteristics, appearing as green, club-shaped organisms adorned with metachromatic granules—dark blue phosphate-containing dots situated at the bacterial poles. When densely packed, they exhibit a unique arrangement reminiscent of Chinese characters. Furthermore, C. diphtheriae is categorized as a fastidious bacterium, necessitating specialized nutrient-enriched media for growth. The commonly utilized medium for cultivating this organism is cysteine-tellurite blood agar, fostering the formation of black colonies by C. diphtheriae.
Toxigenic and Non-Toxigenic Subspecies
All C. diphtheriae subspecies have the potential to be toxigenic or non-toxigenic, contingent upon their ability to produce the diphtheria toxin (DT). DT, a cytotoxic protein, induces harm to host cells. Initially, all subspecies commence as non-toxigenic but transition to toxigenic post-infection by a beta-bacteriophage, a virus that integrates its genetic material with that of the bacteria. Within the beta-bacteriophage genome lie tox-genes responsible for diphtheria toxin synthesis. Consequently, C. diphtheriae gains the capability to produce DT, thus leading to diphtheria.
The DT Complex
The DT complex consists of two primary units, A and B, interconnected by a disulfide bond. Each unit serves a distinct function in invading and harming the host's cells. The B subunit, constituting the larger portion of the DT complex, aids in adhering to the host cell membrane. Following attachment to the host cells, the entire DT complex gradually becomes engulfed by the cell membrane, which forms a sac inwardly, leading to the formation of an endosome. As the endosome resides within the host cell cytoplasm, its internal environment becomes increasingly acidic. Consequently, the disulfide bond linking the two subunits weakens and eventually ruptures, separating them. Subsequently, the A subunit permeates through the endosome membrane into the cytoplasm, where it proceeds directly to the ribosomes. At the ribosomes, the A subunit disrupts cell protein synthesis. This disruption occurs because the A subunit contains an ADP-ribose group, which binds to the elongation factor - EF2, a crucial ribosomal protein involved in connecting amino acids during protein synthesis. This process, known as EF2 ADP-ribosylation, completely disables EF2, halting protein synthesis and ultimately leading to cell demise.
Infection and Transmission
C. diphtheriae primarily induces diphtheria in individuals lacking vaccination or with compromised immune systems. Typically, transmission occurs via respiratory droplets post coughing or sneezing, leading to pharyngeal diphtheria. However, they can also penetrate the body through open skin lesions, resulting in cutaneous diphtheria.
Symptoms and Complications
After inhaling infected respiratory droplets, C. diphtheriae attaches to pharyngeal epithelial cells, releasing DT toxin. This prompts local inflammation, resulting in pharyngeal tissue necrosis and neck swelling. The necrotic tissue accumulates, forming a gray adherent leathery membrane, known as a pseudomembrane. Occasionally, a section of this pseudomembrane may dislodge and become stuck in the trachea or bronchi. If it grows large enough, it can completely obstruct the airways, leading to death by asphyxiation.
If left untreated, the bacteria progressively infiltrates deeper into the pharyngeal wall, eventually entering the bloodstream, where it can disseminate to distant organs like the heart, leading to myocarditis, or inflammation of the heart muscle, and the kidneys, resulting in acute tubular necrosis, or damage to the renal tubules. C. diphtheriae can also migrate to the nerves, inducing nerve demyelination, wherein they damage the myelin sheath enveloping the nerve axons, culminating in polyneuropathy. Diphtheria polyneuropathy typically impacts the oculomotor nerve, resulting in oculomotor palsy, where the muscles governing eye movement are compromised. It can also involve the phrenic nerve, which controls the diaphragm, potentially leading to respiratory difficulties.
Diagnosis and Treatment
Diagnosis of diphtheria primarily involves culturing swabs from the pharynx or suspected skin lesions to isolate C. diphtheriae. Upon a positive culture, the next step is determining if the strain is toxigenic. This is accomplished through Elek's test, where C. diphtheriae is grown on an agar plate containing antitoxin-impregnated filter paper. If the strain produces diphtheria toxin (DT), it reacts with the antitoxin, forming visible precipitate bands. Alternatively, toxigenicity can be detected through PCR, which targets the bacteria's DNA.
Treatment for diphtheria commences promptly upon clinical suspicion, even prior to diagnostic confirmation. It begins with patient isolation to halt further spread, followed by administration of penicillin G or erythromycin if allergic. Subsequently, if the causative bacteria is confirmed toxigenic via Elek’s test, diphtheria antitoxin is administered to counteract the bacterial toxin's effects. Fortunately, there exists a vaccine to prevent diphtheria. This vaccine comprises a toxoid, a modified DT that primes the immune system to confront a genuine infection without inducing tissue damage. Typically, C. diphtheria toxoid is combined with other vaccines against Clostridium tetani, which induces tetanus, and Bordetella pertussis, the cause of whooping cough, forming the DTaP vaccine. This vaccine is administered to children aged 2 months to 6 years.
Summary
Sure, here's a paraphrased version of your provided text while maintaining the structure and order of the original information: Corynebacterium diphtheriae, a gram-positive club-shaped bacterium, is responsible for diphtheria infection. It exhibits characteristics such as being non-motile, aerobic, and non-spore forming. When stained with Albert’s stain, it displays metachromatic granules. Upon infection by a beta bacteriophage, it becomes toxigenic and produces diphtheria toxin, causing tissue destruction and inflammation. Diphtheria manifests as either pharyngeal or cutaneous forms. Pharyngeal diphtheria leads to the formation of a pseudomembrane over the pharynx and larynx, potentially causing airway obstruction if detached. In some cases, the bacteria can disseminate to other organs like the heart, resulting in diphtheria myocarditis, kidneys causing acute tubular necrosis, or nerves leading to diphtheria polyneuropathy. Cutaneous diphtheria presents as chronic shallow skin ulcers. Diagnosis relies on cultures, while treatment involves initiating penicillin G or erythromycin upon clinical suspicion. Diphtheria antitoxin is administered for toxigenic strains.
