When I was in school, I was taught about the 5 kingdoms of life: Monera (all bacteria), and the eukaryotes: Protista, Fungi, Plantae, and Animalia. Since that time, there’s been a bit of a change in the organization. This is largely due to investigation of the Archaea (sometimes still referred to as “archaebacteria”). It was recognized that these organisms were so unlike bacteria (and of course, unlike the eukaryotes) that they deserved their own grouping. Therefore, the most common strategy currently employs 3 domains of cellular life at a level above the kingdom: Bacteria, Eukaryotes, and Archaea.
The archaea have received a lot of attention as “extremophiles:” the microbes that live in environments that have high salinity, very high or low temperatures, or other extremes that make the processes of life daunting. However, they also are residents of more benign locations, such as the human gut, mouth, and vagina. Despite this known association with humans, no species of archaea had ever been identified as a pathogen–until now.
A paper in the April issue of the Journal of Clinical Microbiology reports the identification of archaea in tissue from infected teeth. More specifically, within infected root canals of human teeth–a normally sterile site. Out of 20 cases examined, 5 were found to be positive for methanogens (a type of archae that produces methane as a by-product of metabolism). Because these organisms were found in a site where normal human flora are typically unable to gain access to, the authors suggest this supports the characterization of these archae as pathogens.
A key feature of pathogens that distinguishes them from non-pathogenic organisms is that they need strategies to allow them to gain access to sterile sites within the host; to accomplish this, they also must be able to evade the host’s myriad defenses. How many species of archae have these abilities? The paper notes two reviews published in 2003 that address this topic:
For instance, higher levels of breath methane (produced by methanogens) have been detected in patients with precancerous conditions (ulcerative colitis and colonic polyposis) and cancer of the colon. Cell wall structures of the archaeon Sulfolobus solfataricus have been demonstrated to exhibit toxic activity similar to that of lipopolysaccharides in mice and rabbits, indicating a genetically programmed immune response in those animals that recognizes archaea as potential pathogens. Furthermore, various toxin/antitoxin systems have been found in Methanococcus jannaschii, Archaeoglobus fulgidus, and haloarchaea. In addition, virulence genes for lipopolysaccharide biosynthesis and the tadA gene (e.g., required by Actinobacillus actinomycetemcomitans for nonspecific adherence) have been identified in archaea.
Though these data obviously aren’t conclusive regarding a role played by archaea in disease causation, they are suggestive of one, especially in conjunction with the findings in the current article.
If this is the case, then, how have we missed them until now? Mainly, we didn’t find them because we haven’t been looking. Archaea need special conditions for growth, so traditional culture methods won’t pick them up. Indeed, in this study they relied on a molecular method, detecting the presence of mcrA RNA (a gene which plays a role in methane production) and archaea ribosomal RNA. However, a previous study (Siqueira et al., see below) using a similar method failed to find any archaea in a similar type of infection. Because these organisms aren’t culturable by traditional methods, it’s difficult to know whether you’re missing the targets because they aren’t there, or because your system just isn’t working. Even a positive control in this case may not work 100%, as the positive control would be purified, single-species DNA or RNA, and clinical isolates have the potential to be mixed and may not be the exact same species the primers were designed for.
So, do archaea have the potential to be an emerging pathogen? Will we see more of these types of infections, in which archaea play a role? I think it’s likely. Perhaps they won’t be the sole agent (as they weren’t in this case–they were one part of a polymicrobial infection: an infection involving multiple infectious agents), but they may play a supporting role in the development of disease. Either way, it’s a fascinating line of research, shedding a bit of light on this largely unknown group of organisms that live within so many of us.
Cavicchioli et al. 2003. Pathogenic archae: do they exist? Bioessays. 25:1119-28.
Eckburg et al. 2003. Archaea and their potential role in human disease. Infect Immun. 71:591-6.
Siqueira et al. 2005. Searching for archaea in infections of endodontic origin. J Endod. 31:719-22.
Vianna et al. 2006. Identification and quantification of Archaea involved in primary endodontic infections. J Clin Microbiol. 44:1274-1282.