Treatments for Syphilis: Penicillin G and Linezolid
DOI:
https://doi.org/10.61173/za5ypm35Keywords:
-Syphilis, Penicillin G, Linezolid, Antibiot-ics, Transpeptidase, β-Lactam ringAbstract
Syphilis is a common sexual disease that is transported by body fluid and caused by a spirochete bacterium Treponema pallidum. With the development of antibiotics that are applied to treating syphilis, the number of patients suffering from syphilis has decreased rapidly since 1943, when penicillin antibiotics were started to be introduced as clinical pharmaceuticals to treat syphilis. However, in recent years, the number of patients of syphilis has increased again, 95% of the patients are infected by sexual intercourse. The World Health Organization (WHO) reported that in 2022, nearly 8 million adults who are between 15 and 49 years old acquired syphilis. Because most infections are asymptomatic and unrecognizable during the long incubation period, many people are unconscious of syphilis infection, and they do thus not go to hospitals to check whether they are infected. Penicillin G is a traditional and commonly used antibiotic to treat syphilis by inhibition of production of the complete peptidoglycan cell wall, T.pallidum cells thus burst and die due to osmotic pressure in a hypotonic environment. But penicillin G has been approved for nearly one hundred years to treat syphilis and other diseases bacteria, including T.pallidum has developed the antibiotic-resistance to penicillin G by producing β-lactamase to inactivate penicillin G by opening its β-lactam ring irreversibly. As a result, it is quite urgent and necessary to introduce a new antibiotic to confront syphilis. In 2021, scientific experiments revealed that linezolid, which has been used to treat other Gram-positive bacterial infections for a long time, has impressive effects on treatment for syphilis, indicating that this artificially developed antibiotic could be used clinically to control syphilis by blocking bacterial protein synthesis. In this paper, the symptoms of syphilis and the treatment for syphilis, including penicillin G and linezolid, will be briefly introduced.
References
[1] Tudor, M.E., Al, A.M. and Gossman, W.G. (2023). Syphilis. [online] Nih.gov. Available at: https://www.ncbi.nlm.nih.gov/ books/NBK534780/.
[2] STAMM, L.V. (2014). Syphilis: antibiotic treatment and resistance. Epidemiology and Infection, 143(8), pp.1567–1574. doi: https://doi.org/10.1017/s0950268814002830.
[3] Efficacy of linezolid on Treponema pallidum, the syphilis agent: A preclinical study. (2021). EBioMedicine, [online] 65, p.103281. doi: https://doi.org/10.1016/j.ebiom.2021.103281.
[4] www.niid.go.jp. (n.d.). About Syphilis. [online] Available at: https://www.niid.go.jp/niid/ja/diseases/ha/syphilis/392- encyclopedia/465-syphilis-info.html [Accessed 25 Jul. 2024].
[5] Tantalo, L.C., Lieberman, N.A.P., Pérez-Mañá, C., Suñer, C., Vall Mayans, M., Ubals, M., González-Beiras, C., Rodríguez- Gascón, A., Canut, A., González-Candelas, F., Mueller, J., Tapia, K., Greninger, A.L., Giacani, L. and Mitjà, O. (2023). Antimicrobial susceptibility of Treponema pallidum subspecies pallidum: an in-vitro study. The Lancet Microbe, [online] 4(12), pp.e994–e1004. doi: https://doi.org/10.1016/S2666- 5247(23)00219-7.
[6] Merck Manuals Professional Edition. (n.d.). Syphilis - Infectious Diseases. [online] Available at: https://www. Dean&Francis ISSN 2959-409X merckmanuals.com/professional/infectious-diseases/sexuallytransmitted-infections-stis/syphilis.
[7] Hawley, K.L., Montezuma-Rusca, J.M., Delgado, K.N., Singh, N., Uversky, V.N., Caimano, M.J., Radolf, J.D. and Luthra, A. (2021). Structural Modeling of the Treponema pallidum Outer Membrane Protein Repertoire: a Road Map for Deconvolution of Syphilis Pathogenesis and Development of a Syphilis Vaccine. Journal of Bacteriology, 203(15). doi: https:// doi.org/10.1128/jb.00082-21.
[8] Liu, J., Howell, J.K., Bradley, S.D., Zheng, Y., Zhou, Z.H. and Norris, S.J. (2010). Cellular Architecture of Treponema pallidum: Novel Flagellum, Periplasmic Cone, and Cell Envelope as Revealed by Cryo-Electron Tomography. Journal of molecular biology, [online] 403(4), pp.546–561. doi: https://doi. org/10.1016/j.jmb.2010.09.020.
[9] Radolf, J.D., Deka, R.K., Anand, A., Šmajs, D., Norgard, M.V. and X. Frank Yang (2016). Treponema pallidum, the syphilis spirochete: making a living as a stealth pathogen. PMC.
[10] Fitzgerald, T.J. and Johnson, R.C. (1979). Surface Mucopolysaccharides of Treponema pallidum. Infection and immunity, 24(1), pp.244–251. doi: https://doi.org/10.1128/ iai.24.1.244-251.1979
[11] www.publicdomainfiles.com. (n.d.). Public Domain Picture | A schematic illustration of a cross section of a Treponema pallidum bacterium. | ID: 13530399616091 | PublicDomainFiles.com. [online] Available at: http://www. publicdomainfiles.com/show_file.php?id=13530399616091.
[12] Augustyn, A. (2018). Penicillin | Discovery, Mechanism of Action, & Uses. In: Encyclopædia Britannica. [online] Available at: https://www.britannica.com/science/penicillin.
[13] Mayo Clinic (2019). Syphilis - Diagnosis and treatment - Mayo Clinic. [online] Mayoclinic.org. Available at: https://www. mayoclinic.org/diseases-conditions/syphilis/diagnosis-treatment/ drc-20351762.
[14] STAMM, L.V. (2014). Syphilis: antibiotic treatment and resistance. Epidemiology and Infection, 143(8), pp.1567–1574. doi: https://doi.org/10.1017/s0950268814002830.
[15] World Health Organization (2023). Syphilis. [online] www. who.int. Available at: https://www.who.int/news-room/factsheets/detail/syphilis.
[16] The Modern Epidemic of Syphilis. (2020). New England Journal of Medicine, 382(24), pp.2379–2380. doi: https://doi. org/10.1056/nejmc2006129.
[17] Peeling, R.W., Mabey, D., Kamb, M.L., Chen, X.-S., Radolf, J.D. and Benzaken, A.S. (2018). Syphilis. Nature Reviews Disease Primers, [online] 3(1). doi: https://doi. org/10.1038/nrdp.2017.73.
[18] www.publicdomainfiles.com. (n.d.). Public Domain Picture | A schematic illustration of a cross section of a Treponema pallidum bacterium. | ID: 13530399616091 | PublicDomainFiles.com. [online] Available at:
[19] Dunlop, E.M.C. (1974). Penicillin and the control of syphilis. American Heart Journal, 88(4), pp.395–400. doi: https://doi.org/10.1016/0002-8703(74)90198-7.
[20] Golden, M.R., Marra, C.M. and Holmes, K.K. (2003). Update on Syphilis. JAMA, 290(11), p.1510. doi: https://doi. org/10.1001/jama.290.11.1510.
[21] Jefferiss, F.J.G. and Willcox, R.R. (1963). Treatment of Early Syphilis with Penicillin Alone. Sexually Transmitted Infections, 39(3), pp.143–148. doi: https://doi.org/10.1136/ sti.39.3.143.
[22] Smith, C.A., Kamp, M., Olansky, S. and Price, E.V. (1956). Benzathine penicillin G in the treatment of syphilis. PubMed, 15(6), pp.1087–96.
[23] LEIFER, W. (1945). THE TREATMENT OF EARLY SYPHILIS WITH PENICILLIN. Journal of the American Medical Association, 129(18), p.1247. doi: https://doi. org/10.1001/jama.1945.02860520015004. http://www.publicdomainfiles.com/show_file. php?id=13530399616091.
[24] www.osmosis.org. (n.d.). Argyll Robertson Pupil: What Is It, Causes, and More | Osmosis. [online] Available at: https:// www.osmosis.org/answers/argyll-robertson-pupil.
[25] Dichter, S.L. and Shubert, G.S. (2020). Argyll Robertson Pupil. [online] PubMed. Available at: https://www.ncbi.nlm.nih. gov/books/NBK537179/.
[26] PubChem (2019). Penicillin g. [online] Nih.gov. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/Penicillin-g.
[27] Gurarie, M. (2023). What to Know About Penicillin G. [online] Verywell Health. Available at: https://www. verywellhealth.com/penicillin-g-5075834.
[28] Nawfa, R., Purnomo, A.S. and Putro, H.S. (2019). Synthesis of Antibiotic Penicillin-G Enzymatically by Penicillium chrysogenum. Asian Journal of Chemistry, 31(10), pp.2367– 2369. doi: https://doi.org/10.14233/ajchem.2019.21766.
[29] Rosenberg, J. (2005). How Alexander Fleming Discovered Penicillin. [online] ThoughtCo. Available at: https://www. thoughtco.com/alexander-fleming-discovers-penicillin-1779782.
[30] Hashemian, S.M., Farhadi, T. and Ganjparvar, M. (2018). Linezolid: a review of its properties, function, and use in critical care. Drug Design, Development and Therapy, [online] Volume 12, pp.1759–1767. doi: https://doi.org/10.2147/dddt.s164515.
[31] www.chemspider.com. (n.d.). Benzylpenicillin | C16H18N2O4S | ChemSpider. [online] Available at: https:// www.chemspider.com/Chemical-Structure.5693.html.
[32] BioTechnology Notes. (2018). Penicillin: Biosynthesis, Structure, Fermentation Process and Uses. [online] Available at: https://www.biotechnologynotes.com/antibiotics/penicillin/ penicillin-biosynthesis-structure-fermentation-process-anduses/13843.
[33] Lehninger, A.L., Nelson, D.L. and Cox, M.M. (2005). Lehninger principles of biochemistry. 4th ed. New York: W.H. Freeman.
[34] Martin, J.F., Alvarez-Alvarez, R. and Liras, P. (2022). Dean&Francis Yuhang Li Penicillin-Binding Proteins, β-Lactamases, and β-Lactamase Inhibitors in β-Lactam-Producing Actinobacteria: Self- Resistance Mechanisms. International Journal of Molecular Sciences, 23(10), p.5662. doi: https://doi.org/10.3390/ ijms23105662.
[35] Clegg, C.J. and Davis, A. (2023). Biology for the IB Diploma Third edition. Hodder Education.
[36] Reece, J.B., Urry, L.A., Cain, M.L., Alexander, S., Minorsky, P.V., Jackson, R.B. and Campbell, N.A. (2014). Campbell biology. 10th ed. Boston: Pearson.
[37] Clement, M.E., Okeke, N.L. and Hicks, C.B. (2014). Treatment of syphilis: a systematic review. JAMA, [online] 312(18), pp.1905–17. doi: https://doi.org/10.1001/ jama.2014.13259.
[38] Chemistry LibreTexts. (2016). 25.2: Structure and Stereochemistry of the Amino Acids. [online] Available at: https:// chem.libretexts.org/Bookshelves/Organic_Chemistry/Map%3A_ Organic_Chemistry_(Wade)_Complete_and_Semesters_I_and_ II/Map%3A_Organic_Chemistry_(Wade)/25%3A_Amino_ Acids_Peptides_and_Proteins/25.02%3A_Structure_and_ Stereochemistry_of_the_Amino_Acids.
[39] https://www.facebook.com/Drugscom (2017). Penicillin G Injection. [online] Drugs.com. Available at: https://www.drugs. com/pro/penicillin-g-injection.html.
[40] Enna, S.J. and Bylund, D.B. (2008). XPharm : the comprehensive pharmacology reference. Amsterdam: Elsevier, pp.1–6.
[41] Stuart, M.C. and World Health Organization (2009). WHO model formulary 2008. Geneva: Who.
[42] Ford, C., Zurenko, G. and Barbachyn, M. (2001). The Discovery of Linezolid, the First Oxazolidinone Antibacterial Agent. Current Drug Target -Infectious Disorders, 1(2), pp.181– 199. doi: https://doi.org/10.2174/1568005014606099.
[43] www.webmd.com. (n.d.). Linezolid Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD. [online] Available at: https://www.webmd.com/drugs/2/drug- 18168-6154/linezolid-oral/linezolid-oral/details.
[44] PubChem (n.d.). Linezolid. [online] pubchem.ncbi.nlm.nih. gov. Available at: https://pubchem.ncbi.nlm.nih.gov/compound/ Linezolid#section=2D-Structure.
[45] www.chemspider.com. (n.d.). Linezolid | C16H20FN3O4 | ChemSpider. [online] Available at: https://www.chemspider.com/ Chemical-Structure.390139.html?rid=091d92e4-1936-4aeba901-662dde278204&page_num=0.
[46] Liu, A.H. (2008). Innate microbial sensors and their relevance to allergy. 122(5), pp.846–858. doi: https://doi. org/10.1016/j.jaci.2008.10.002.
[47] Russell, M.G. and Jamison, T.F. (2019). Seven‐Step Continuous Flow Synthesis of Linezolid Without Intermediate Purification. Angewandte Chemie International Edition, 58(23), pp.7678–7681. doi: https://doi.org/10.1002/anie.201901814.
[48] Davey, S.G. (2019). Seven steps, no stops. Nature Reviews Chemistry, 3(5), pp.289–289. doi: https://doi.org/10.1038/ s41570-019-0102-6.
[49] Zhang, X., Chen, W., Li, C. and Wu, X. (2009). An efficient and practical synthesis of antibacterial linezolid. Journal of Chemical Research, 2009(12), pp.739–740. doi: https://doi.org/1 0.3184/030823409x125905758886078.
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