Do all Gram negative bacteria cause septic shock? If they don't could they if you attacked them with an antibiotic that could lyse the cell? For example any antibiotic that attacks the cell wall, although I suppose that could be difficult with the gram negative wall, not to many gram negatives are susceptible to a wall attack.


2 Answers 2


all Gram negative bacteria can potentially cause septic shock, but septic shock is not limited to Gram negative cell wall lipopolysaccharides. Any infectious agent can cause septic shock, including gram positive and gram negative bacteria, fungi and even viruses (this is quite evident in the recent Ebola outbreak).[1]

The causative agents for sepsis/septic shock have evolved. Originally strongly considered to be related to Gram-negative bacteria, that is no longer the case. About 25 years ago, sepsis was considered to be a response to endotoxin thought to be relatively specific for Gram-negative bacteria. That Gram-negative bacteria were the most common causes of sepsis[2] resulted in trials that focused on specific therapies for G negative endotoxins.

It is now recognized that sepsis may occur from bacterial, fungal and viral organisms. More recent epidemiology studies reveal that Gram-positive bacteria have become the most common cause of sepsis in the past 25 years. According to the most recent estimates in sepsis, there are approximately 200,000 cases of Gram-positive sepsis each year, compared with approximately 150,000 cases of Gram-negative sepsis.[3]

Fungal causes of sepsis have also grown at a rapid pace. Why this occurs may be two-fold: a general increase in nosocomial (hospital acquired) cases of sepsis, and more effective treatment of bacterial infections, thus promoting fungal infections to a more leading role. The increase of fungal nosocomial infections has also shifted away from the common Candida albicans organism to the more recalcitrant torulopsis, glabrata and krusei subspecies.[4]

So while the Gram negative Lipopolysaccharide or “endotoxin” is unique to Gram negative bacteria, cell components of Gram positive bacteria have been identified that appear to be biologically equivalent to endotoxin in stimulating the inflammatory response associated with sepsis and septic shock. These include a peptidoglycan layer outside the cell membrane of Gram positive bacteria as well as non-peptidoglycan polymers (such as the teichoic acids). They have been shown to stimulate the release of cytokines, specifically tumor necrosis factor and interleukin-1.[5]

[1] How Ebola Kills You: It's Not The Virus
[2] Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy
[3] The epidemiology of sepsis in the United States from 1979 through 2000.
[4] Nosocomial bloodstream infections. Secular trends in rates, mortality, and contribution to total hospital deaths.
[5] Sepsis and Septic Shock
Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes

  • $\begingroup$ Regarding your connection to Ebola: As far as I remember the clinic in Hamburg decribed that the main problem with sepsis came from bacteria which leaked from the gut into the blood stream, causing problems. But this is most likely due to effects that the virus caused, so this is a bit of a hen and egg problem. $\endgroup$
    – Chris
    Nov 17, 2014 at 7:25
  • $\begingroup$ Without directly addressing your comment's content, I can say that a common misconception about septic shock is that it is a result of pathogens in the bloodstream. It's not. Septic shock in Ebola is due to a cytokine storm. Ebola virus appears to trigger a release of pro-inflammatory cytokines with subsequent vascular leak and impairment of clotting ultimately resulting in multi-organ failure and shock. The gut stuff is the result of GI end-organ failure. $\endgroup$ Nov 17, 2014 at 8:51
  • $\begingroup$ Ok, this was an unclear formulation. Viable bacteria in the blood stream can be considered as one of the ultimate dangers. But still substances like LPS (which can cause septic shock) will find an entry route here. $\endgroup$
    – Chris
    Nov 17, 2014 at 8:56
  • $\begingroup$ @Chris - That's a good point. If you're interested in the medical side of this, here is some very interesting reading: Approaches to Clinical Management for Patients with Ebola Treated in U.S. Hospitals. It goes through everything we know about Ebola in the US-treated patients (except from Dallas). I didn't see any mention of positive blood cultures even in the patient requiring ventilatory support and dialysis (so very close to death). $\endgroup$ Nov 17, 2014 at 9:31

The major factor defining Gram-negative (vs. Gram-positive) bacteria is the structure of the cell wall, outer membranes, and the moieties that extend out into the environment:

Gram+ vs. Gram-


Gram+ bacteria have an inner plasma membrane and an outer, thick layer of peptidoglycans. This is what takes up Gram's stain. Gram-, on the other hand, have a plasma membrane, a thinner peptidoglycan wall, then an outer membrane consisting of lipopolysaccharides (also known as LPS or endotoxin) anchored into the membrane's phospholipids, along with various proteins within the membrane:

Gram- outer membrane structure


Sepsis, a systemic inflammatory response syndrom (SIRS) can be caused by both Gram-positive and -negative bacteria, as well as viruses and fungi. In the case of Gram-negatives, the immune system is activated in response to the presence of LPS from extracellular lysed and intracellular antigen-processed bacteria, through the Toll-like receptor TLR4/CD14/MD-2 pathway. One can have a local infection, and still not develop sepsis. However, if the infection becomes large enough or the bacteria enter the blood stream in significant numbers, sepsis can occur. Not all patients with sepsis develop septic shock, which is characterized not only by a microorganism-caused SIRS and organ dysfunction/hypoperfusion, but also by chronic hypotension (low blood pressure) even after administration of IV fluids.

Structurally, LPS contains the highly-conserved Lipid A, which anchors the molecule into the outer membrane, a core oligosaccharide, and the outer O-antigen:

LPS structure


Lipid A is actually the most toxic segment of LPS (the portion recognized by TLR4 and MD-2), and while it is generally highly-conserved among different bacterial strains and species, studies have shown that different human-pathogenic species of bacteria have altered Lipid A from the "canonical" structure derived from E. coli. This can cause variations in the downstream signaling from TLR4 to NF-κB, potentially leading to immune system evasion.

So, to directly address your question:

Do all Gram negative bacteria cause septic shock?

They can, if present in sufficient quantities, but not necessarily through the same mechanisms. The immune system recognizes many different pathogen-associated molecular patterns (PAMPs) through a variety of TLRs and other pattern recognition receptors (PRRs) like C-type lectin receptors, Nod1 and Nod-like receptors, etc. Some work on intact bacteria, others recognize intracellular epitopes. Therefore, sepsis and, in severe cases, septic shock, can be caused by Gram-negative bacteria through LPS-independent pathways. While it's possible that lysing these bacteria chemically by antibiotics could potentially enhance the immune response, cells like macrophages are very good at recognizing foreign invaders and lysing them on their own, giving plenty of substrates to the various receptors. Also, keep in mind that dead cells may auto-lyse, so the antibiotics need not necessarily attack the cell wall itself, just kill the bacteria.


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