NC State University

Research Reviews

Are antibiotics the only potential cure to Nosema ceranae?

Answer: For now, yes, but new exciting technologies are on the horizon

Not to further alarm any hypochondriacs or intense germaphobes out there, but if you stop and think about it, it's amazing that we're not always sick. As I write this, I'm sitting on an airplane next to a beautiful sweet one-year-old little girl who is completely adorable except for the small fact that she's constantly hacking up a lung. If I were to have superman vision, I would be able to see clouds of millions of small virus particles swirling in the airspace around us. And that's only one example; one could easily imagine all of the microbes around us that are eagerly awaiting their chance to infect us.

So what even gives us a fighting chance? Our immune system, obviously. Quite a remarkable invention of nature, really. All of the parasites and pathogens that might otherwise invade our bodies are covered with signature-shaped proteins. Our immune system has no means of predicting which bugs we might encounter, nor does it know ahead of time how to recognize them. To overcome this, we produce millions of different forms of proteins ourselves, known as antibodies, with each form able to randomly recognize a single protein like a lock fits a key, some of which—by chance—precisely match a particular pathogen. When a match is made, the rest of our immunological machinery kicks into high gear, making every attempt to cleanse the invader before it has a chance to multiply and make us sick.

For centuries now, we've been given a leg-up in this fight against the microbial world by vaccinating ourselves against some of the nastier bugs out there. The way this works is to be given very small doses of the disease agent (usually dead so that it doesn't actually cause disease) so that our immune system recognizes the signature-shaped proteins, produce the appropriate antibodies, and have all of our immunological ducks in a row in the event we're ever exposed again in the future. Vaccinations are arguably the most effect means of disease prevention in human history, and their efficacy is without question or equivocation.

Honey bee immune systems are very different from ours, so different in fact that I won't even bother trying to summarize the steps here, but needless to say that they face the same microbial challenges. Compared to other (solitary) insects, honey bees are actually more susceptible to microbe exposure because they have an estimated one-third fewer immune genes than expected (arguably because their social behavior helps them prevent disease exposure and transmission). One important parasite that has been gaining increased prominence is the adult gut microsporidian Nosema ceranae. Living in the intestines of adult bees, it can cause damage to their digestive tract, dysentery, and reduced lifespans. Our bees tend to be quite susceptible to this new strain of nosema, since they don't have an adapted evolutionary history to combat infections. Currently, the only means of treatment for beekeepers is to provide an antibiotic (fumagilin) to clean out the infection.

It would be very nice, therefore, to develop alternate means of prevention, treatment, and control of nosema. One such emerging technology is known as RNAi, the 'i' standing for "interference." The Nobel Prize for Medicine and Physiology was recently awarded to its developer, as it stands to have as much of an impact on the practice of medicine in the future as vaccines have over the last century. For all living things to grow and reproduce, they need to create proteins that are encoded in their molecular code. The mediators of this process is RNA, so any disruption in an important RNA molecule can render a microbe helpless. Providing small "anti-sense" RNA molecule can do this, much like turning off a light switch.

An exciting new study, recently published in the journal Applied And Environmental Microbiology, explores the use of RNAi technology in its control of nosema. The authors developed RNA molecules that knocked out specific genes in Nosema ceranae that were critical to their growth and development. These RNAi molecules are 100% specific to that species, so that they are unable to work on anything else in nature (including honey bees). They then took newly emerged nurse bees, inoculated them with at least 100,000 nosema spores by feeding them infected sugar syrup, and then kept them in cages in the laboratory. Furthermore, half of the bees were also fed syrup with the RNAi transcript in it as well. All bees were then sacrificed at different daily intervals and measured for nosema prevalence (by measuring levels of known nosema genes). Sure enough, those fed the RNAi had significantly lower levels of nosema, suggesting a means by which it may be controlled.

The RNAi technology is a hopeful new approach to combating infections. It isn't permanent, it doesn't negatively affect the bees in any way (because they, by definition, don't have the genes targeted by the RNA molecule), and—unlike the use of antibiotics—nosema is exceedingly unlikely to develop any resistance to it (because the targeted genes are so fundamental to their growth and reproduction). This technology is therefore more analogous to vaccinating bees against infection than it is to controlling it with pesticides, only the vaccination doesn't permanently change the host. There is much, much more work to do in this area, as such a powerful approach needs complete certainty before it can be utilized, but there is significant hope that this technology may provide a quantum leap forward in helping to keep our bees healthy.

Reference

Paldi, N., Eitan G., M. Oliva, Y. Zilberberg, L. Aubin, J. Pettis, Y. Chen, and Jay D. Evans. (2010). Effective gene silencing in a microsporidian parasite associated with honeybee (Apis mellifera) colony declines. Applied And Environmental Microbiology, 76: 5960–5964.