Gram-positive sepsis. Mechanisms and differences from gram-negative sepsis.
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.
Sriskandan
S
S
Department of Infectious Diseases, Imperial College School of Medicine, Hammersmith Hospital, London, United Kingdom.
Cohen
J
J
D000818:Animals; D001426:Bacterial Proteins / Q000633:toxicity; D001427:Bacterial Toxins / Q000633:toxicity; D050260:Carbohydrate Metabolism; D002473:Cell Wall / Q000737:chemistry; D004768:Enterotoxins / Q000633:toxicity; D005098:Exotoxins; D016908:Gram-Positive Bacterial Infections / Q000201:enzymology / Q000209:etiology* / Q000276:immunology; D006801:Humans; D008565:Membrane Proteins / Q000633:toxicity; D010457:Peptidoglycan / Q000378:metabolism; D018805:Sepsis / Q000201:enzymology / Q000276:immunology / Q000382:microbiology*; D018089:Superantigens; D013682:Teichoic Acids / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D005098:Exotoxins; D008565:Membrane Proteins; D010457:Peptidoglycan; C117980:SpeA protein, Streptococcus pyogenes; D018089:Superantigens; D013682:Teichoic Acids; D014409:Tumor Necrosis Factor-alpha; C030107:enterotoxin F, Staphylococcal