The Naegleria fowleri loves to twist and scroll by amoeboid movement, we know. What is the catch for it to go up the cribriform plate and enter less oxygenated zones of anterior cranial fossa to phagocytize the olfactory bulbs and frontal lobe? It has to be chemo or food attraction for the amoebae to go that high. I am working on the signaling chemotactic stimuli to answer this question.
Best,
Abdul Mannan Baig
Dear Abdul
It seems the low oxygen pressure in upper part of nose canal and frontal lobe of brain is one of important causes for Naegleria spp colonization in these parts because the amoeba are microaerophil. Hope to help.
Abdul,
I am not sure there is an answer to your exact question, but it is known that free-living Naegleria flagellate stages disperse much more quickly than many other amoeboid species or forms. Little is known about tropisms in this genus, but there is a growing body of research on variations between pathogenic and non-pathogenic strains in terms of peptidases and other enzymes that can degrade tight junction proteins, extracellular matrices, etc, that would normally provide barriers to invasion of the nervous system. One recent paper is:
Journal of Eukaryotic Microbiology 62: 51-59, (2015) by Francine Marciano-Cabral and her colleagues. References in that paper will lead you to more.
It may be that Naegleria is not attracted to the nervous system for selective migration at all. Perhaps Naegleria is simply a high-rate, broad-scale disperser by strategy, seeking to colonize any suitable environment possible. If a strain that ends up in the nasal passages happens to possess the appropriate pre-adaptive biochemical characteristics to disrupt cellular and extracellular neural barriers, that particular strain becomes invasive.
Best wishes with your work!
Bruce
Abdul,
By the way, on a related topic, I've attached below a couple of papers from my research in which we showed ultrastructural evidence that a particular trematode parasite that specifically invades the brain of fish actually dismantles the neural tissue of its host by breaking apart the bonds between cells (i.e., presumably junctions and extracellular matrices), while leaving the neural cells intact. Not exactly your system, but interesting nonetheless in terms of mechanisms of brain invasion by parasites.
Best wishes,
Bruce
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Dear David Bruce,
Great, the answers and suggestions are brilliant. I have a question, keeping in mind of what you proposed that maybe it is a random ascend to the Brain, the anatomy of the upper part of nose has several other venues on sides like sinuses and non-olfactory mucosa, why we do not see any invasion there? Maybe there is a neural chemotactic ligand that attracts them, because they seem to be migrating up-hill in there natural course to get to the olfactory bulb and frontal lobe of the brain.
I will, of course go the papers you have sent. I have a little clue of a chemical that it finds as chemotactic. If you or other readers find this project interesting I am thinking of a collaborative work on this and a mutual paper if we get the right answer.
Best,
Dr. Abdul Mannan
Dear Dr. Abdul Mannan,
It is also very important to note that much of the the brain is an immunologically privileged site with lower immune response against many pathogens. It could be that the Naegleriado invade other neighboring tissues, but are quickly overcome by the immune response in those sites. There are so many unanswered questions in this fiel, and I applaud your research efforts. I have linked below to one of our recent papers on a related pathogen, Acanthamoeba, infecting the eye.
Best wishes,
Bruce
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Great as always, your comments are very valuable Bruce. Will keep you posted on it, as work is in progress.
Best wishes dear,
Mannan
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