Key Lyme Disease Transmission Factor Identified – Could it Help Reduce Risk?

by lmatthews on December 30, 2013

hrpa lyme disease transmission

Removing the HrpA gene cuts Lyme disease transmission by affecting bacterial mobility.

Lyme disease is caused by the bacterium Borrelia burgdorferi which is transmitted via tick bite to mammals like humans, deer, moose, dogs, cats, and even horses. Studies have shown that the risk of being infected by a tick that is attached and feeding for less than 24 hrs is minimal, at least in species of tick in the USA.

However, risk of transmission could be reduced even further following identification of a key factor in transmission, a protein that unwinds bacterial RNA (riboxynucleic acid).

Publishing their findings in the December issue of PLoS Pathogens, George Chaconas and colleagues, of the Snyder Institute for Chronic Diseases at the University of Calgary, Canada, identified HrpA as essential for transmission of bacteria from ticks to mammalian hosts. HrpA is an RNA helicase which means that it can take energy from the cell and use it to unwind RNA. Unwinding RNA alters how it is then translated into proteins, affecting the activity of the cell. HrpA was previously identified by Chaconas as modulating expression of proteins in the Lyme disease bacteria.

RNA and DNA and Lyme Disease

Cells contain DNA (dioxyribonucleic acid) and RNA with the DNA like a mastercopy of an organism’s genetic profile and the RNA used to translate the instructions into physical things like proteins.

This latest study involved Justin Radolf and Melissa Caimano from the University of Connecticut Health Center, USA, who worked with Chaconas and colleagues to look at the activity of HrpA in order to find out exactly what effect it has on protein expression and, therefore, on the lifecycle and activity of the bacterium.


What are Helicases and Why do they Matter?

RNA helicases are common in bacteria but little is really known about how they work and no others had been identified in B. burgdorferi. The helicase in question here appears to take energy in the form of adenosine triphosphate (ATP) and use it to unwind (think of ‘heli’ like in helicopter) the strands of RNA so that they are then easier to translate into other proteins. Removing the gene that codes for production of HrpA could, theoretically, reduce the capacity for RNA translation and bacterial reproduction and activity.

Stopping Lyme Disease Transmission

What the researchers noted here is that altering the genetic profile of B. burgdorferi so that it did not contain the HrpA gene led to it being unable to infect mice in the laboratory. This was tested by directly injecting both normal and mutant bacteria into mice and then testing tissue samples and blood samples after a week and up to four weeks after injection. No mutant bacteria were able to be found whereas non-mutated bacteria containing the HrpA gene were present in all tissues.

To test the transmission via a normal route, i.e. tick bite, another group of lab mice were deliberately exposed to infected ticks. While the bacteria did grow and survive in the ticks they were unable to move from the midgut to the saliva, thereby preventing transmission. The researchers also tested the area of skin around tick bites on the mice immediately after the ticks fell off and found no mutant bacteria.

Helping Prevent Lyme Disease

This research suggests that HrpA is significant in allowing the Lyme disease bacteria to infect animals and be transmitted successfully via tick bites. It could be that in the coming months or years scientists can use this knowledge to aid Lyme disease vaccine development and/or other Lyme disease prevention strategies by disrupting the bacteria’s ability to reproduce effectively.

Reference


Pierre-Olivier Hardy, Justin D. Radolf, Melissa J. Caimano, George Chaconas, Aydan Salman-Dilgimen, HrpA, an RNA Helicase Involved in RNA Processing, Is Required for Mouse Infectivity and Tick Transmission of the Lyme Disease Spirochete, PLoS Pathogens, December 19, 2013DOI: 10.1371/journal.ppat.1003841

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