Diphtheria

University of Oklahoma Study Abroad Microbiology in Arezzo, Italy[1]

Etiology/Bacteriology

Taxonomy

| Domain = Bacteria | Phylum = Actinobacteria | Order = Actinomycetales | Family = Corynebacteriaceae | Genus = Corynebacterium | Species = C. diphtheria

Description

Corynebacterium diphtheriae is a gram-positive, non-motile, aerobic, and rod-shaped bacterium that causes diphtheria. There are four main subspecies that have been recognized: C. diphtheriae mitis, C. diphtheriae intermedius, C. diphtheriae gravis, and C. diphtheriae belfanti. C. diphtheriae gravis has the fastest generation time out of the four, allowing it to impose its toxic effects sooner. They can all be characterized as toxigenic or non-toxigenic, or those causing diphtheria and those that don’t, respectively. Diphtheria is an upper respiratory tract infection initially resulting in a sore throat and mild fever, but can progress to other more serious symptoms if not treated [1]. It can also infect the skin when lesions are exposed to the bacteria. Even though there are thousands of reported cases each year, the threat of contracting or succumbing to this illness has dramatically decreased due to advancements in antibiotic treatment and development of vaccinations [2].

Pili

The pili found on the surface of C. diphtheriae are beneficial in the adherence to host cells. There are three distinct types of pili expressed including SpaA-, SpaD-, and SpaH- (Spa for sortase-mediated pilus assembly). They are all structurally similar, but have different functions. SpaA- specifically allows for the adherence to pharyngeal epithelial cells, while SpaD- and SpaH- display specificity for binding to lung and laryngeal epithelial cells. There are also two minor pili, SpaB and SpaC proteins, that only bind to pharyngeal cells. The presence of these various pili on C. diphtheriae help it to adhere to certain surfaces, which is necessary for colonization of the host [3].

Toxin

The main virulence factor of C. diphtheriae is diphtheria toxin (DT), an exotoxin, released by the bacteria after entering the human body. DT is classified as an AB toxin because it has two components, one for activation and one for binding. Unlike many other toxins, DT is encoded by a bacteriophage, and it also secreted when extracellular iron levels become low. The major function of the toxin is to enter the cytoplasm and inhibit protein synthesis in susceptible host cells [4]. After the termination of protein synthesis, the production of deoxyribonucleic acid and ribonucleic acid is decreased, and energy metabolism is secondarily affected. All of these factors ultimately lead to cell death [5]. The toxin is carried throughout the body via the bloodstream to reach distant organs, which can occasionally cause paralysis or congestive heart failure [6].

Adherence

The exact mechanism of adherence by the pili is not known, but many studies have been conducted to formulate a reasonable proposal. It has been discovered that the two minor pili, SpaB and SpaC, are not only found in the pilus, but are also arranged on the bacterial cell wall in monomeric and heterodimeric forms. The binding of SpA- to pharyngeal epithelial cells can be attributed to these two pili. Since these adhesins are found in two forms, as a fiber and intricate proteins on the cell surface, they can mediate both distant and nearby contacts during the initial adherence of the pathogen and its succeeding colonization [7]. If either minor pili is absent, then adherence to the host cells is greatly diminished. Little is known about the steps that the SpaD- and SpaH- pili take to adhere to the lung and laryngeal epithelial cells, but it is still postulated that they play an imperative role in the process [8].

References

1 Online Textbook of Bacteriology. Diphtheria

2 Burkovski, A. (2014). Corynebacterium diphtheriae and related toxigenic species: Genomic, Pathogenicity, and Applications. New York: Springer

3 Ton-That H., Schneewind O. (2003). Assembly of pili on the surface of Corynebacterium diphtheriae. Mol Microbiol 50(4):1429-1438

4 Frassetto, L. A.(2006) Corynebacterium infections

5 Collier, J. (1975). Diphtheria Toxin: Mode of Action and Structure. Bacteriological Reviews 39(1) 54-60

6 Murphy, J. R. (1996). Corynebacterium Diphtheriae. In: Baron S, editor. Medical Microbiology. 4th edition. Galveston (TX): University of Texas Medical Branch at Galveston

7 Broadway, M. M., Rogers, E. A., Chang, C., Huang, I.-H., Dwivedi, P., Yildirim, S., … Ton-That, H. (2013). Pilus Gene Pool Variation and the Virulence of Corynebacterium diphtheriae Clinical Isolates during Infection of a Nematode. Journal of Bacteriology, 195(16), 3774–3783

8 Mandlik, A., Swierczynski, A. Das, A. and Ton-That, H. (2007). Corynebacterium diphtheriae employs specific minor pilins to target human pharyngeal epithelial cells. Molecular Biology 64(1), 111-124