Pathogenic archaebacteria: do they not exist because archaebacteria use different vitamins?

Sir, Recently in these pages, Cavicchioli et al. addressed an interesting question, namely: do pathogenic archaebacteria exist? In themain, they cite evidence to establish the following points. (1)Noarchaebacteria haveyet been found tobeagents of disease. (2) Archaebacteria are sufficiently abundant in non-extreme environments as to provide them ample opportunity to infect animals and humans. (3) Some archaebacteria interact intimately with eukaryotes as intracellular symbionts, the best-known examples being methanogens that inhabit the cytosol of eukaryotes that possess hydrogenosomes. (4) Methanogens are very commonly found as inhabitants of the human oral cavity and intestinal tract, though no clear-cut link between methanogen presence and any disease has yet emerged. (5) Some archaebacteria appear to possess toxins, although no toxicity to humans or animals is known. (6) Secretion systems associated with eubacterial pathogenicity and with pathogenicity islands seem to occur in fragmentary form among archaebacterial genomes, suggesting that the wellknown mobility of these genes does not seem to have altogether missed the archaebacteria as recipients. (7) There are some human diseases to which no causative agent has been assigned, leaving the possibility open that archaebacteria might ultimately be found to be responsible. From those seven basic observations, none of which I would contend in any way, they surmise in conclusion that ‘‘There are two possible reasonswhynopathogenic archaeaare known: (1) theydonot exist or (2) they have not been identified.’’ They continue ‘‘From our reasearch, there are no compelling reasons to suppose the first possibility.’’ However, considering the present question from an entirely different standpoint (simple biochemistry), I think that there are compelling reasons, which I wish to briefly mention here, to suppose that archaebacterial pathogens do not exist. In a nutshell, the answer to the question of why there are no archaebacterial pathogens is probably: ‘‘cofactors’’ (also called ‘‘vitamins’’ in the context of nourishment). Archaebacteria synthesize and use in their day-to-day biochemistry a variety of cofactors that humans, animals, eukaryotes in general, and most eubacteria for that matter, neither synthesize nor require. A fewexamplesaremethanopterin (aC1donating cofactor with similar spectrum of functions as folic acid), coenzyme M (a methyl carrier), factor F430 (a nickelcontaining porphyrin analogue involved in methyl transfer), factor F420 (a hydride carrier like riboflavin), coenzyme B (a thiol-containing cofactor involved in redox reactions), methanofuran (involved in CO2 reduction), cobamids (corrinoids that can be viewed as anaologues of cobalamin), alternative quinones such as sulfur-containing heterocyclic benzothiophenes or methanophenazine (not a quinone at all but used by many archeabacteria instead of quinones), halocyanin (an alternative to cytochromes), and so on, and so forth. Vitamins are important for nourishment, they are essential components of the diet for those organisms, such as humans, that are unable to synthesize all of the vitamins (or even amino acids) that they need to survive. Pathogens, like every other organism on earth, are looking for a meal. The underlying themes of pathogen evolution among eubacteria seem to be (1) gain access to a host, (2) learn to avoid host defence and (3) undergo genome reduction by virtue of the ability to parasitize the host’s biochemistry. Mesophilic archaebacteria should not havea fundamental problemwith the first two steps, but arguably have an insurmountable problem with the third step. By no means do I purport to be an expert on the topic of archaebacterial cofactors, but I have read that some exist. In fairness, the papers cited here deal mainly with methanogens (one group of archaebacteria). But looking around, basic biochemistry in archaebacteria seems to be different enough to consider the suggestion that the lack, in eukaryotic cells, of what an archaebacterium would perceive as a good meal, would make eukaryotes fundamentally uninteresting as a substrate for infection and growth. As an example, consider the glycolytic pathway, familiar to most of us from textbooks, which operates without the participation of NAD (or any other niacin homologue) in some archaebacteria, and with the help of enzymes that, in the majority, do not share common ancestry with their eubacterial and eukaryotic homologues, notwithstanding the circumstance that relatively few archaebacteria even have an Embden–Meyerhof type glycolytic pathway. As a main course at dinnertime, the cell content of eukaryotes in general and humans in particular, does not provide a complete diet for archaebacteria, except for some autotrophs in those eukaryotes that have hydrogenosomes, because for many archaebacterial autotrophs, H2 is almost a completemeal. That brings us back to the universal tree, according to which eukaryotes and archaebacteria should tend to use the same cofactors, which they don’t. Rather, eukaryotes and eubacteria tend to use the same cofactors, probably for the simple reason that eukaryotes inherited most of their biochemistry from their mitochondrial symbiont. From these considerations a simple prediction follows: if archaebacterial ‘‘pathogens’’ are found, they will infect other archaebacteria—not eukaryotes—and one such example seems already to have been described.