Masquerading microbial pathogens: capsular polysaccharides mimic host-tissue molecules

FEMS Microbiol Rev. 2014 Jul;38(4):660-97. doi: 10.1111/1574-6976.12056. Epub 2014 Jan 27.

Abstract

The increasing prevalence of antibiotic-resistant bacteria portends an impending postantibiotic age, characterized by diminishing efficacy of common antibiotics and routine application of multifaceted, complementary therapeutic approaches to treat bacterial infections, particularly multidrug-resistant organisms. The first line of defense for most bacterial pathogens consists of a physical and immunologic barrier known as the capsule, commonly composed of a viscous layer of carbohydrates that are covalently bound to the cell wall in Gram-positive bacteria or often to lipids of the outer membrane in many Gram-negative bacteria. Bacterial capsular polysaccharides are a diverse class of high molecular weight polysaccharides contributing to virulence of many human pathogens in the gut, respiratory tree, urinary tract, and other host tissues, by hiding cell surface components that might otherwise elicit host immune response. This review highlights capsular polysaccharides that are structurally identical or similar to polysaccharides found in mammalian tissues, including polysialic acid and glycosaminoglycan capsules hyaluronan, heparosan, and chondroitin. Such nonimmunogenic coatings render pathogens insensitive to certain immune responses, effectively increasing residence time in host tissues and enabling pathologically relevant population densities to be reached. Biosynthetic pathways and capsular involvement in immune system evasion are described, providing a basis for potential therapies aimed at supplementing or replacing antibiotic treatment.

Keywords: bacterial pathogens; capsular polysaccharides; combating antibiotic resistance; glycosaminoglycans; immune system evasion; polysialic acid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Host-Pathogen Interactions / immunology*
  • Humans
  • Immune Evasion / genetics
  • Immune Evasion / immunology*
  • Molecular Mimicry / immunology
  • Polysaccharides / chemistry
  • Polysaccharides / immunology
  • Polysaccharides / metabolism
  • Polysaccharides, Bacterial / chemistry
  • Polysaccharides, Bacterial / genetics
  • Polysaccharides, Bacterial / immunology*
  • Polysaccharides, Bacterial / metabolism

Substances

  • Polysaccharides
  • Polysaccharides, Bacterial