Endotoxins - a structural link between cyanobacteria and human pathogens

Lipopolysaccharides (LPS), also known as endotoxins, are a major structural building block of the Gram-negative bacterial outer membrane (Figure 1). They contribute to a great extent to the microbes’s structural integrity and protect them from certain chemicals, hence help to survive harsh environmental conditions. Besides protecting (cyano-) bacteria from chemical stress, LPS is a strong trigger for the innate immune system of animals.

Lipopolysaccharides consist of three domains (see also Figure 2):

1. the outer (O) antigen – a long, repetitive sugar polymer, 
2. the core oligosaccharide – containing few, but often uncommon sugar moieties 
3. lipid A – a highly conserved, glucosamine disaccharide with multiple fatty acids attached, anchoring the large molecule into the bacterial membrane.

From the three domains, lipid A is responsible for much of the toxicity of Gram-negative bacteria. If cells are lysed and LPS is released to the blood, for example during infection and antibiotic treatment, the lipid A moiety may cause fever, diarrhoea or fatal septic shock by triggering many defensive mechanisms of the innate immune system at once.

Cyanobacteria also belong to the group of Gram-negative bacteria and contain LPS in their outer membrane. Despite this analogy, the cyanobacterial LPS structure is slightly different to the LPS of heterotrophic bacteria. Even though cyanobacterial LPS might be a reason for common symptoms of cyanobacterial poisoning in the gastrointestinal tract, including nausea, vomiting and diarrhoea, there is controversy among scientists about the effects of cyanobacterial LPS: opposed to bacterial LPS, some reports even suggest a suppression of the immune response upon cyanobacterial LPS exposure.

Eventually, LPS is seldom considered the toxic agent itself. It rather modulates adverse effects of other cyanobacterial metabolites. For example, it may contribute to disrupt the gastrointestinal barrier upon ingestion and thereby facilitate the uptake of cyanobacterial toxins like microcystins, consequently increasing the pathological effect. Speaking of synergistic effects, it also needs to be mentioned that naturally occurring cyanobacterial blooms are very heterogeneous communities also comprised of heterotrophic bacteria. Hence, under environmental exposure conditions to biomass mixtures, bacterial LPS may play an important immunomodulatory role as well as cyanobacterial LPS. Concluding, there is rising concern about cyanobacterial LPS potentially contaminating resources of drinking water and the hazard has to be further investigated.

References and further reading:

• Bernardová, K., Babica, P., Maršálek, B., & Bláha, L. (2008). Isolation and endotoxin activities of lipopolysaccharides from cyanobacterial cultures and complex water blooms and comparison with the effects of heterotrophic bacteria and green alga. Journal of Applied Toxicology, 28(1), 72–77. https://doi.org/10.1002/jat.1257
• Bláhová, L., Adamovský, O., Kubala, L., Švihálková Šindlerová, L., Zounková, R., & Bláha, L. (2013). The isolation and characterization of lipopolysaccharides from Microcystis aeruginosa, a prominent toxic water bloom forming cyanobacteria. Toxicon, 76, 187–196. https://doi.org/10.1016/J.TOXICON.2013.10.011
• Funari, E., & Testai, E. (2008). Human Health Risk Assessment Related to Cyanotoxins Exposure. Critical Reviews in Toxicology, 38(2), 97–125. https://doi.org/10.1080/10408440701749454
• Stewart, I., Schluter, P. J., & Shaw, G. R. (2006). Cyanobacterial lipopolysaccharides and human health – a review. Environmental Health, 5(1), 7. https://doi.org/10.1186/1476-069X-5-7

Figures

• Figure 1: modified from https://en.wikipedia.org/wiki/Gram-negative_bacteria.
  Jeff Dahl - Own work, 'Diagram of a gram-negative cell wall.' 
• Figure 2: https://en.wikipedia.org/wiki/Lipopolysaccharide. en:User:Lmaps and User:TimVickers - Modified version of en:Image:Kdo2 lipidA.png
  Structure of the (3-deoxy-D-manno-octulosonic acid)2 Lipid A endotoxin from E. coli K-12