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A vaccine to tackle antibiotic resistance

Dr. K. Shanthi, Assistant Professor, Department of Biochemistry, Kalinga University, Raipur

Abstract

Antibiotic- resistant infections, or infections resistant to conventional treatment, have been a longstanding public health concern.  Experts suggest that within few decades, many treatments might not work anymore against infections that are usually treatable. This is particularly true in the case of Staphylococcus aureus (S. aureus) including methicillin – resistant Staphylococcus aureus (MRSA), which are some of the most frequent causes of infections. This urgency has led researchers to find new ways to fight against antimicrobial resistance. While the conventional method for vaccine development often focuses on targeting specific antigens associated with a virus or bacteria, researchers have now taken an innovative approach by developing vaccines that target carbohydrates as the “target” antigen.

Key words

Antibiotic- resistant infections, Staphylococcus aureus (S. aureus), methicillin – resistant Staphylococcus aureus (MRSA), poly-β-(1-6)-N-acetylglucosamine (PNAG)

 

Bacterial infections continue to remain a significant threat to global health, and this situation is worsened by the widespread prevalence of antimicrobial-resistant strains, including those resistant to multidrug. In 2019, it was estimated by the Center for Disease Control and Prevention that about 3 million antimicrobial – resistant infections occurred annually1. Antibiotic resistance is rising to alarming levels in all parts of the world, with some pathogens showing resistance to nearly all the available antibiotics2. This highlights the urgent need to develop new strategies to prevent and treat infections. In parallel with the development of new antibiotics, vaccination has also become an important approach for combating pathogens 3.

Despite the success of multiple anti-microbial vaccines against many infections such as clostridium tetani, Bordetella pertussis etc, there are currently no approved vaccines against many other deadly pathogens including S.aureus 4,5. Selecting a suitable antigen poses a major challenge in vaccine design. The cell wall of S.aureus contains the polysaccharide known as poly-β-(1-6)-N-acetylglucosamine (PNAG). This polysaccharide is primarily made up of glucosamine units linked by β (1-6) bonds, with around 80-90% of them N-acetylated6-9. PNAG present on the cell surface and also as an internal component of the biofilm, this polysaccharide has been found to have an important virulence factor that aids S. aureus evade the immune system10. Moreover, PNAG’s widespread expression in various pathogenic microbes and its pivotal roles in disease progression or pathogenesis make it an attractive target for vaccine development.

Highlights of PNAG-based vaccines

  • PNAG-based vaccines provide effective protection against lethal S. aureus challenges.
  • It also effectively protects from MRSA-induced death.
  • It provides defence in both acid and passive immunity models.
  • These vaccines significantly reduce bacterial load in the kidney.
  • PNAG-based vaccines do not significantly disturb the gut microbiome
  • They are biocompatible and have no adverse side effects.

PNAG- based vaccine is a powerful strategy to develop the next generation vaccines and more effectively fight against pathogen infections including those by drug resistant strains 11.

 

Reference

  1. 2019 AR threats report. https://www.cdc.gov/drugresistance/ biggest-threats.html (2021).
  2. Uddin, T. M. et al. Antibiotic resistance in microbes: history, mechanisms, therapeutic strategies and future prospects. J. Infect. Public Health 14,1750–1766 (2021).
  3. Micoli, F., Bagnoli, F., Rappuoli, R. & Serruto, D. The role of vaccines in combatting antimicrobial resistance. Nat. Rev. Microbiol. 19, 287–302 (2021).
  4. Deadly Staph infections still threaten the U.S. https://www. cdc.gov/media/releases/2019/p0305-deadly-staph-infections.html (2024).
  5. Moellering, R. C. Jr MRSA: the first half century. J. Antimicrob. Chemother. 67,4–11 (2011). Maira-Litran, T. et al. Immunochemical properties of the staphylo coccal poly-N-acetylglucosamine surface polysaccharide. Infect. Immun. 70, 4433–4440 (2002).
  6. Maira-Litran, T. et al. Immunochemical properties of the staphylococcal poly-N-acetylglucosamine surface polysaccharide. Infect. Immun. 70, 4433–4440 (2002).
  7. Cywes-Bentley, C. et al. Antibody to a conserved antigenic target is protective against diverse prokaryotic and eukaryotic pathogens. Proc.NatlAcad.Sci.USA110, E2209–E2218 (2013).
  8. Nicholson, T. L. et al. The Bordetella Bps polysaccharide is required for biofilm formation and enhances survival in the lower respiratory tract of swine. Infect. Immun. 85,e00261–00217 (2017).
  9. Low, K. E. & Howell, P. L. Gram-negative synthase-dependent exo-polysaccharide biosynthetic machines. Curr.Opin.Struct.Biol.53, 32–44 (2018).
  10. Skurnik, D., Cywes-Bentley, C. & Pier, G. B. The exceptionally broad based potential of active and passive vaccination targeting the conserved microbial surface polysaccharide PNAG. Expert Rev. Vaccines 15,1041–1053 (2016).
  11. Tan Z, Yang W, O’Brien NA, Pan X, Ramadan S, Marsh T, Hammer N, Cywes-Bentley C, Vinacur M, Pier GB, Gildersleeve JC. A comprehensive synthetic library of poly-N-acetyl glucosamines enabled vaccine against lethal challenges of Staphylococcus aureus. Nature Communications. 24;15(1):3420 (2024)

 

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