Host, pathogen, and ... ammonia?

In  either a happy accident or a particularly clever piece of scheduling, there were two talks back to back in todays ISAAH program that dealt with the role of ammonia (NH3) in fish diseases.  But these two talks gave surprisingly different perspectives on the role of this nitrogen waste compound in the mechanism of disease.

In the first, Ron Thune from LSU talked about a bacterial disease of catfish cased by Edwardsiella ictaluri.  Edwardsiella is an obligate intracellular parasite of macrophages, which is to say that the bacterium must live inside a host cell, in this case a the major scavenging cell in the immune system.  How does that work, that a parasites can (indeed NEEDS to) live inside the very cell that the host would use to attack it?  In a normal macrophage, an offending bacterium would be engulfed in a small bubble in the cell called a vacuole, and the macrophage would drop the pH inside that vacuole, to kill the bacterium.  Edwadsiella cannot survive at those sorts of low and corrosive pH’s, but it cleverly produces ammonia, which forms a sort of pH buffering system that raises the pH to a level where E. ictaluri not only survives but thrives.  What makes this unusual is that ammonia is normally a waste product that is in itself toxic to many biochemical systems.  The idea that a pathogen uses this waste chemical to improve its own conditions is fascinating.

In the second, even more surprising talk, Drew Mitchell looked at a different bacterial disease called columnaris.  Some other researchers had noticed that fish survival in the face of columnaris outbreaks was better in cruddy water quality, which is totally counter-intuitive.  So Drew and his co-authors did a controlled study of the progression and resolution of columnaris disease at different concentrations of ammonia in their water; ammonia being the greatest component of excreted fish waste.  Sure enough, at concentrations of the toxic unionised form of ammonia that most folks would avoid for fear of killing their fish (0.4ppm and higher), the columnaris agent was effectively eliminated and fish survival actually increased!  The idea that a toxic metabolic waste product could serve to protect a fish from a pathogenic bacterium was, to me, completely counter-intuitive and surprising!  We would normally think of ammonia as an environmental stressor that might make a fish MORE susceptible to disease, not less.  What Drew discovered was more like the protection against the malaria parasite conferred on people by the genetic disease sickle cell anaemia.

Lets recap for a second.  The first study showed that a bacterium can use ammonia to create conditions conducive to survival within host cells, making a disease worse.  The second showed that ammonia can (somehow, as yet unspecificed) protect fish from a different bacterial pathogen, making the disease better.  I guess it goes to show that any single chemical player can have a range of roles in the complex biological landscape of disease, and that we have to be careful about thinking that any given chemical is “good” or “bad”.  Best of all, both studies involve a big element of surprise, and that always makes biology fun and exciting.