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Causes of Corynebacterium Diphtheriae Infections

Discuss about the Corynebacterium Diphtheriae Infections.

Once upon a time, when the world was still dealing with other deadly pathogens, troubling humankind with respiratory tract related diseases, a new contender was preparing to steal the show with its antics management. I had the honour of causing one of the widely known infectious diseases, Diphtheria. May be it is not entirely necessary, but the opening credits of my story needs to be handed down to Edwin Klebs (Farfour et al., 2012). In the year 1883, he had made the effort of introducing me to the world as the causative organism for the disease Diphtheria, popularly known as the ‘strangling angel of children’ (Byard, 2013). Now that was some fancy name. However, only limited imagination leads to some name like Corynebacterium diphtheriae. I cannot entirely blame them given that the word ‘Diphther’ has Greek origin, which stands for ‘membrane’ (Goldman and Green, 2014). I was isolated from the pseudo membrane in the pharynx, which was a resultant of the necrotic toxin that I am able to produce (Goldman and Green, 2014). Well, the family needs a mention here and therefore a rough outline has been drawn in figure 1 to typically portray my heredity. Before humanity wipes my name from the face of Earth, maybe it is time that I should present myself, tell my story in my own words, my glorified days of terror.

My popularity was extremely short lived, thanks to Freidrich Loeffler (Doyle et al., 2017). Yes, this man decided to end my tyranny in the year 1884 by spilling my secrets in front of the whole world. He had discovered that I could be cultured only from the nasopharyngeal cavity (Burkovski, 2016). He was also responsible for revealing my secret potent weapon to the world, the diphtheria toxin. He had stated that the toxin was capable of causing damage to organs. I was too sure about myself; I knew I could terrorize the world a little longer. Then it was not very long when Emil von Behring, in the year 1890, brought my terror to a standstill when he landed up isolating the antitoxin against diphtheria from blood samples, collected from a horse infected with diphtheria (Gillespie, Bamford and Bamford, 2012). He was also responsible for developing the first vaccine in the year 1913 against the diphtheria toxin (Burkovski, 2014). My brothers in arms, Corynebacterium ulcerans and Corynebacterium pseudotuberculosis, are also able to produce the diphtheria toxin (de Mattos et al., 2014). However, the process of infecting the host, which may consist of both human and animal, greatly differs from mine. 

Symptoms of Corynebacterium Diphtheriae Infections

I have been known to be a Gram-positive organism, and I am known to be aerobic in nature (Gillespie, 2014). I am non-motile and do not have a capsule, however, I am club shaped. Figure 2 somewhat depicts me in my true form, however, I beg to differ. I am more glorified in appearance that just a rod-shaped bacilli on a microscopic field. My cell wall consists of sugars such as arabinose, mannose and galactose. My favourite source of nutrition happens to be nicotinic and patothenic acids (Reardon-Robinson et al., 2015). Based on the biochemical properties that I possess, I can be described as gravis, mitis, intermedius and belfanti (Clinton et al., 2013). I am known to cause the disease diphtheria, an infectious disease, which is transmitted through respiratory droplets. I locally colonize the mucosa of several anatomical sites within the body of the host, they include, pharyngeal, laryngeal, umbilical, genital, nasal, cutaneous, conjunctival (Zasada, 2013). The pharynx and larynx are my favourite spots for manifestation and therefore on colonization management, necrotic membranes appear that are either grey, translucent or black in colour. The pseudomembrane that I form consists mainly of fibrin, inflammatory cells.

The colonization also results in the enlargement of the lymph nodes, which restricts swallowing, and breathing by the host as the lumen of the larynx and pharynx narrows (Sangal et al., 2015). The size of the neck increases too. My potent weapon of destruction, the toxin is able to damage the fibres of the cardiac muscle resulting in the blockage of the heart (Peixoto et al., 2014). My toxin is even capable of demyelinating the nerves, paralysing the palate and the ocular muscles (Gillespie, Bamford and Bamford, 2012). My infamous toxin consists of two fragments, namely N-terminal fragment A and a fragment B (Cohen and Van Heyningen, 2012). The N-terminal fragment A is known as the catalytic domain and it is responsible in catalyzing the NAD+ dependent ADP- ribolysation of EF2. This spews trouble for the eukaryotic cells as the protein synthesis is inhibited (Sekura, 2012). On the other hand, fragment B consists of the transmembrane and receptor binding domains that are responsible for helping me bind to the cell surface receptor and helps me in delivering the fragment A into the cytosol (Sekura, 2012). I like the extent of destruction I am able to cause. The extent of fatality the toxin can bring about, as little as 100-150 ng/kg of body weight rather makes me giddy.

Treatment for Corynebacterium Diphtheriae Infections

However, the penny had just dropped and I had soon realized my limitations. The life threatening effect of my toxin can be easily neutralized with an antitoxin. The swift application of the diphtheria antitoxin (DAT) along with a conjunct antibiotic therapy happens to cure the people (Both et al., 2014). Now that was some serious bad news for me.

I must admit, it was a very difficult job to maintain the top spot in being a respiratory tract related disease-causing pathogen. With the combating solutions being devised by humanity, it was getting difficult to keep up. Efficient and methodical immunization programs have helped several developed countries to control me. However, nobody could save them from my wrath for very long. I have happened to make a grand entry in the scene by terrorizing the eastern European countries in my wake (Wagner et al., 2012). These countries are some of the most popular tourist destinations in the world. Due to the resultant collapse of the immunization programs, the risk of occurrence of diphtheria has increased in these parts. Now that is one bit of good news for me.

As long as humanity does not devise improved DAT’s, I will keep coming back. After all, it is an expensive process and therefore it is not even available in adequate quantity for every individual. There are only very few places in the world that manufacture these drugs. Popularly known producers of DAT are Microgen (Moscow) and Vins Bioproducts (Hyderabad) (Zasada, 2015). I should be worried if the preclinical studies involving the Anti-diphtheria monoclonal antibodies (mAbs) become successful (Sevigny et al., 2013). PCR-based diagnostic methods can also prove to be a headache (Both et al., 2013). It will get difficult to pose as a health threat henceforth. The immunization program of DTP3 vaccination among infants as seen in the year 2016 has been shown in the figure 3. Funny, they only realized the emergency when they found the number of infected to rise. I was feeling important all over again.

Over the years, several improved detection methods for the detection of the diphtheria toxin has been developed. Worrisome, thoroughly worrisome for me as one can see. Methods such as Immunochromatographic strip test (ICS), Cytotoxicity test, Matrix-assisted-laser-desorption/ionization time-of-flight mass-spectrometry (MALDI-TOF) and Elek ouchterlony test management (Berger et al., 2014).

Then I do not think I will be able to continue this for very long. Figure 4 seem to show the reduction in the reported cases of diphtheria over years stretching from 1980 to 2016. Human beings are snooping into my genetic makeup and are working towards the molecular basis that defines my pathogenicity (Both et al., 2015). If appropriate typing methods could be used then even the epidemics could also be predicted. Oh, how terribly it can spell disaster for me. MLST (Multi Locus Sequence Typing) has been able to avoid several limitations faced by previous researchers by analyzing the information related to the nucleotide within the selected housekeeping genes (Both et al., 2015). Then there are these groups of people, dedicated towards a pangenomics project, which might just help me, get a bigger place on the evolution map as a human pathogen (Trost et al., 2012). My days might just finally be over if humankind succeeds to establish it. The epidemiology and the pathogenesis of my non-toxigenic strains have to be thoroughly studied though. Until then I do not wish to bid adieu and continue in living up to my reputation of being a hellion. 

Prevention of Corynebacterium Diphtheriae Infections

References:

Berger, A., Hogardt, M., Konrad, R. and Sing, A., 2014. Detection methods for laboratory diagnosis of diphtheria. In Corynebacterium diphtheriae and related toxigenic species (pp. 171-205). Springer Netherlands.

Both, L., Banyard, A.C., van Dolleweerd, C., Wright, E., Ma, J.K.C. and Fooks, A.R., 2013. Monoclonal antibodies for prophylactic and therapeutic use against viral infections. Vaccine, 31(12), pp.1553-1559.

Both, L., Collins, S., de Zoysa, A., White, J., Mandal, S. and Efstratiou, A., 2015. Molecular and epidemiological review of toxigenic diphtheria infections in England between 2007 and 2013. Journal of clinical microbiology, 53(2), pp.567-572.

Both, L., White, J., Mandal, S. and Efstratiou, A., 2014. Access to diphtheria antitoxin for therapy and diagnostics. Euro Surveill, 19(24), pp.2-2.

Burkovski, A., 2014. Diphtheria and its etiological agents. In Corynebacterium diphtheriae and Related Toxigenic Species (pp. 1-14). Springer Netherlands.

Burkovski, A., 2016. Corynebacterium diphtheriae and related toxigenic species. Springer.

Byard, R.W., 2013. Diphtheria–‘The strangling angel’of children. Journal of forensic and legal medicine, 20(2), pp.65-68.

Centre for Disease Prevention and Control (CDC). Diphtheria. https://www.cdc.gov/diphtheria/about/photos.html [Accessed on 29th Aug 2017]

Clinton, L.K., Bankowski, M.J., Shimasaki, T., Sae-Ow, W., Whelen, A.C., O'Connor, N., Kim, W. and Young, R., 2013. Culture-negative prosthetic valve endocarditis with concomitant septicemia due to a nontoxigenic Corynebacterium diphtheriae biotype Gravis isolate in a patient with multiple risk factors. Journal of clinical microbiology, 51(11), pp.3900-3902.

Cohen, P. and Van Heyningen, S. eds., 2012. Molecular action of toxins and viruses (Vol. 2). Elsevier.

Collins, M.D. and Cummins, C.S., 1986. Genus Corynebacterium. Bergey's manual of systematic bacteriology, 2, pp.1266-1276.

de Mattos Guaraldi, A.L., Hirata, J.R. and de Carvalho Azevedo, V.A., 2014. Corynebacterium diphtheriae, Corynebacterium ulcerans and Corynebacterium pseudotuberculosis—General aspects. In Corynebacterium Diphtheriae and Related Toxigenic Species (pp. 15-37). Springer Netherlands.

Doyle, C.J., Mazins, A., Graham, R.M., Fang, N.X., Smith, H.V. and Jennison, A.V., 2017. Sequence Analysis of Toxin Gene–Bearing Corynebacterium diphtheriae Strains, Australia. Emerging infectious diseases, 23(1), p.105.

Farfour, E., Badell, E., Zasada, A., Hotzel, H., Tomaso, H., Guillot, S. and Guiso, N., 2012. Characterization and comparison of invasive Corynebacterium diphtheriae isolates from France and Poland. Journal of clinical microbiology, 50(1), pp.173-175.

Gillespie, S., Bamford, K. and Bamford, K.B., 2012. Medical microbiology and infection at a glance. John Wiley & Sons.

Gillespie, S.H., 2014. Medical microbiology illustrated. Butterworth-Heinemann.

Goldman, E. and Green, L.H. eds., 2015. Practical handbook of microbiology. CRC Press.

Peixoto, R.S., Pereira, G.A., dos Santos, L.S., Rocha-de-Souza, C.M., Gomes, D.L.R., dos Santos, C.S., Werneck, L.M.C., de Oliveira, A.A.D.S., Hirata Jr, R., Nagao, P.E. and Mattos-Guaraldi, A.L., 2014. Invasion of endothelial cells and arthritogenic potential of endocarditis-associated Corynebacterium diphtheriae. Microbiology, 160(3), pp.537-546.

Reardon?Robinson, M.E., Osipiuk, J., Jooya, N., Chang, C., Joachimiak, A., Das, A. and Ton?That, H., 2015. A thiol?disulfide oxidoreductase of the Gram?positive pathogen Corynebacterium diphtheriae is essential for viability, pilus assembly, toxin production and virulence. Molecular microbiology, 98(6), pp.1037-1050.

Sekura, R. ed., 2012. Pertussis toxin. Elsevier.

Sangal, V., Blom, J., Sutcliffe, I.C., von Hunolstein, C., Burkovski, A. and Hoskisson, P.A., 2015. Adherence and invasive properties of Corynebacterium diphtheriae strains correlates with the predicted membrane-associated and secreted proteome. BMC genomics, 16(1), p.765.

Sevigny, L.M., Booth, B.J., Rowley, K.J., Leav, B.A., Cheslock, P.S., Garrity, K.A., Sloan, S.E., Thomas, W., Babcock, G.J. and Wang, Y., 2013. Identification of a human monoclonal antibody to replace equine diphtheria antitoxin for treatment of diphtheria intoxication. Infection and immunity, 81(11), pp.3992-4000.

Trost, E., Blom, J., de Castro Soares, S., Huang, I.H., Al-Dilaimi, A., Schröder, J., Jaenicke, S., Dorella, F.A., Rocha, F.S., Miyoshi, A. and Azevedo, V., 2012. Pangenomic study of Corynebacterium diphtheriae that provides insights into the genomic diversity of pathogenic isolates from cases of classical diphtheria, endocarditis, and pneumonia. Journal of bacteriology, 194(12), pp.3199-3215.

Wagner, K.S., White, J.M., Lucenko, I., Mercer, D., Crowcroft, N.S., Neal, S., Efstratiou, A. and Diphtheria Surveillance Network, 2012. Diphtheria in the postepidemic period, Europe, 2000–2009. Emerging infectious diseases, 18(2), p.217.

World Health Organization (WHO). Immunization Surveillance, assessment and monitoring. https://www.who.int/immunization/monitoring_surveillance/burden/diphtheria/en/ [Accessed on 29th Aug 2017]

Zasada, A.A., 2013. Nontoxigenic highly pathogenic clone of Corynebacterium diphtheriae, Poland, 2004–2012. Emerging infectious diseases, 19(11), p.1870.

Zasada, A.A., 2015. Corynebacterium diphtheriae infections currently and in the past. Przegl Epidemiol, 69, pp.439-444.

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