Nanobodies – a New Superhero in Tick-Borne Infections

Every kid loves a superhero. Then we grow up… and still look for superheroes, especially if we work in medicine.  Our medical superheroes are needed for the disease or condition which is ravaging our patients’ lives.  A tick-borne disease called ehrlichiosis succumbs to only one conventional medicine superhero, the antibiotic doxycycline.  Should ehrlichiosis ever learn to overpower doxycycline, then we will have much more trouble with Ehrlichia than we already do.  Researchers in this study report a possible new superhero contender called nanobodies.

You have to admit that the name “nanobodies” does kind of roll off the tongue.  You can close your eyes and see the microscopic nanobody diving into the infected cell to disarm the enemy microbe, saving the day.

The invading bacteria, Ehrlichia chaffeensis, rides inside a tick until it bites the unsuspecting new host.  Once inside a human host, the bacteria grows inside our cells which make it more difficult for our immune system to reach.  Bacteria like staphylococcus and streptococcus grow outside cells and offer easier targets for antibodies and immune cells, but Ehrlichia’s ability to grow inside cells makes it a dangerous foe.  While we may hear more about Lyme disease, Ehrlichia chafeensis puts up its own impressive numbers and can even cause death in a few.

Researchers knew that the size of antibodies produced by our immune system were too large to enter cells where the Ehrlichia grow.  They also knew that medical therapies typically attack microbes at only one step in their life cycle.  As they worked with lab produced antibodies against Ehrlichia in cell cultures, they identified ones with strong efficacy and began to trim off unnecessary parts of the antibodies.  They wanted the smallest portions of the antibody which could attach to the Ehrlichia invader and could enter cells where they grew.

With time and effort they found an antibody from which they derived a nanobdy against a Ehrlichia protein called Etf-1.  This protein allows Ehrlichia to prevent cells from apoptosis or programmed cell death in which the cells commit cellular suicide to stop multiplication of the bacteria inside them.  The bacteria use this blocking mechanism to keep the cells alive long enough to grow a bunch more bacteria.  By blocking this protein, this apoptosis would prevent bacterial reproduction.

The produced nanobody inhibited this protein at 3 different steps in the process which gave hope to the researchers that the therapy would be effective in animals.  Normally, antibiotics attack a microbe at one step in its life cycle, but a three-pronged approach by this nanobody would likely increase its strength against Ehrlichia.  When testing in lab mice, bacterial growth was greatly inhibited by the nanobody versus mice who did not receive the therapy.

The researchers view this particular nanobody not as a final answer, but as a first step. They hope to develop further nanobody options against other enemy proteins and processes over the coming years.  They also see opportunities for other superpowers against cancers or neurodegenerative diseases where a single dysfunctional protein could be targeted leading to a cure.  Those of us practicing functional medicine appreciate the creativity of such research as we continue applying the best of both natural and conventional medicine to patients in 2021 and beyond.  As we delve into a better understanding of our enemies and our defense systems, we can derive better therapies from both science and nature.

Original Article:

Wenqing Zhang, Mingqun Lin, Qi Yan, Khemraj Budachetri, Libo Hou, Ashweta Sahni, Hongyan Liu, Nien-Ching Han, Jeffrey Lakritz, Dehua Pei, Yasuko Rikihisa. An intracellular nanobody targeting T4SS effector inhibits Ehrlichia infection. Proceedings of the National Academy of Sciences, 2021; 118 (18): e2024102118 DOI: 10.1073/pnas.2024102118

Thanks to Science Daily:

Ohio State University. “Using nanobodies to block a tick-borne bacterial infection: In cells and mice, tiny molecules stop bacteria from hijacking cells.” ScienceDaily. ScienceDaily, 28 April 2021. www.sciencedaily.com/releases/2021/04/210428133006.htm