Gram-positive sepsis. Mechanisms and differences from gram-negative sepsis

Infect Dis Clin North Am. 1999 Jun;13(2):397-412. doi: 10.1016/s0891-5520(05)70082-9.


This article has reviewed the mechanisms by which gram-positive bacteria lead to septic shock, with regard to bacterial structure and toxicology and the host responses elicited both in animal models and in the clinical setting. Gram-positive organisms are better suited to invade host tissues and elicit, in general, a brisker phagocytic response than gram-negative organisms. The lack of endotoxin in the outer cell wall is compensated for by the presence of exposed peptidoglycan and a range of other toxic secreted products. It appears that cell wall components of gram-positive bacteria may signal via the same receptor as gram-negative endotoxin, although the type of signal and coreceptor may differ. Both animal and clinical data suggest that, unlike endotoxin-mediated shock, gram-positive infection produces a modest TNF response only and does not respond well to anti-TNF therapies. This leads one to conclude that the mechanisms leading to shock in gram-positive infection may be multifactorial and perhaps more difficult to treat. A thorough review of gram-positive mechanisms of sepsis is hampered by a lack of basic research in this field. Understanding of gram-negative bacterial structure and the regulation of virulence genes is at an advanced stage, yet the molecular tools to analyse virulence factors in the gram-positive genome have only recently become available. There is a paucity of good animal models of gram-positive infection and a lack of microbiologic data from some of the major trials in sepsis that might have given greater insight into the mechanisms leading to shock in various infections.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Bacterial Proteins / toxicity
  • Bacterial Toxins / toxicity
  • Carbohydrate Metabolism
  • Cell Wall / chemistry
  • Enterotoxins / toxicity
  • Exotoxins*
  • Gram-Positive Bacterial Infections / enzymology
  • Gram-Positive Bacterial Infections / etiology*
  • Gram-Positive Bacterial Infections / immunology
  • Humans
  • Membrane Proteins / toxicity
  • Peptidoglycan / metabolism
  • Sepsis / enzymology
  • Sepsis / immunology
  • Sepsis / microbiology*
  • Superantigens*
  • Teichoic Acids / metabolism
  • Tumor Necrosis Factor-alpha / metabolism


  • Bacterial Proteins
  • Bacterial Toxins
  • Enterotoxins
  • Exotoxins
  • Membrane Proteins
  • Peptidoglycan
  • SpeA protein, Streptococcus pyogenes
  • Superantigens
  • Teichoic Acids
  • Tumor Necrosis Factor-alpha
  • enterotoxin F, Staphylococcal