Navigation Links
Scientists reveal quirky feature of Lyme disease bacteria

Scientists have confirmed that the pathogen that causes Lyme Diseaseunlike any other known organismcan exist without iron, a metal that all other life needs to make proteins and enzymes. Instead of iron, the bacteria substitute manganese to make an essential enzyme, thus eluding immune system defenses that protect the body by starving pathogens of iron.

To cause disease, Borrelia burgdorferi requires unusually high levels of manganese, scientists at Johns Hopkins University (JHU), Woods Hole Oceanographic Institution (WHOI), and the University of Texas reported. Their study, published March 22, 2013, in the Journal of Biological Chemistry, may explain some mysteries about why Lyme Disease is slow-growing and hard to detect and treat. The findings also open the door to search for new therapies to thwart the bacterium by targeting manganese.

"When we become infected with pathogens, from tuberculosis to yeast infections, the body has natural immunological responses," said Valeria Culotta, a molecular biologist at the JHU Bloomberg School of Public Health. The liver produces hepcidin, a hormone that inhibits iron from being absorbed in the gut and also prevents it from getting into the bloodstream. "We become anemic, which is one reason we feel terrible, but it effectively starves pathogens of iron they need to grow and survive," she said.

Borrelia, with no need for iron,has evolved to evade that defense mechanism. In 2000, groundbreaking research on Borrelia's genome by James Posey and Frank Gherardini at the University of Georgia showed that the bacterium has no genes that code to make iron-containing proteins and typically do not accumulate any detectable iron.

Culotta's lab at JHU investigates what she called "metal-trafficking" in organismsthe biochemical mechanisms that cells and pathogens such as Borrelia use to acquire and manipulate metal ions for their biological purposes.

"If Borrelia doesn't use iron, what does it use?" Culotta asked.

To find out, Culotta's lab joined forces with Mak Saito, a marine chemist at WHOI, who had developed techniques to explore how marine life uses metals. Saito was particularly intrigued because of the high incidence of Lyme Disease on Cape Cod, where WHOI is located, and because he specializes in metalloproteins, which contain iron, zinc, cobalt, and other elements often seen in vitamin supplements. The metals serve as linchpins, binding to enzymes. They help determine the enzymes' distinctive three-dimensional shapes and the specific chemical reactions they catalyze.

It's difficult to identify what metals are within proteins because typical analyses break apart proteins, often separating metal from protein. Saito used a liquid chromatography mass spectrometer to distinguish and measure separate individual Borrelia proteins according to their chemical properties and infinitesimal differences in their masses. Then he used an inductively coupled plasma mass spectrometer to detect and measure metals down to parts per trillion. Together, the combined analyses not only measured the amounts of metals and proteins, they showed that the metals are components of the proteins.

"The tools he has are fantastic," Culotta said. "Not too many people have this set of tools to detect metalloproteins."

The experiments revealed that instead of iron, Borrelia uses that element's next-door neighbor on the periodic chart, manganese, in certain Borrelia enzymes. These include an amino peptidase and an important antioxidant enzyme called superoxide dismutase.

Superoxide dismutase protects the pathogens against a second defense mechanism that the body throws against them. The body bombards pathogens with superoxide radicals, highly reactive molecules that cause damage within the pathogens. Superoxide dismutase is like an antioxidant that neutralizes the superoxides so that the pathogens can continue to grow.

The discoveries open new possibilities for therapies, Culotta said. "The only therapy for Lyme Disease right now are antibiotics like penicillin, which are effective if the disease is detected early enough. It works by attacking the bacteria's cell walls. But certain forms of Borrelia, such as the L-form, can be resistant because they are deficient in cell walls."

"So we'd like to find targets inside pathogenic cell that could thwart their growth," she continued. "The best targets are enzymes that the pathogens have, but people do not, so they would kill the pathogens but not harm people." Borrelia's distinctive manganese-containing enzymes such as superoxide dismutase may have such attributes.

In search of new avenues of attack, the groups are planning to expand their collaborative efforts by mapping out all the metal-binding proteins that Borellia uses and investigating biochemical mechanisms that the bacteria use to acquire manganese and directs it into essential enzymes. Knowing details of how that happens offers ways to disrupt the process and deter Lyme Disease.


Contact: Media Relations Office
Woods Hole Oceanographic Institution

Related biology news :

1. Scientists create new tools for battling secondhand smoke
2. Academy scientists receive top honors for long-term research and training initiatives in Mongolia
3. Scientists discover reasons behind snakes shrinking heads
4. U of T scientists map genome that causes Dutch Elm Disease
5. Scientists discover novel chemical that controls cell behavior
6. 87 scientists elected to the American Academy of Microbiology
7. New book celebrates women scientists in the Americas
8. Stanford scientists calculate the carbon footprint of grid-scale battery technologies
9. Scientists discover distant relatives of gardeners friend
10. Monell scientists help identify a missing link in taste perception
11. UF scientists discover new crocodilian, hippo-like species from Panama
Post Your Comments:
Related Image:
Scientists reveal quirky feature of Lyme disease bacteria
(Date:11/9/2015)... DUBLIN , Nov. 09, 2015 /PRNewswire/ ... announced the addition of the "Global ... to their offering. --> ... "Global Law Enforcement Biometrics Market 2015-2019" ... Research and Markets ( ) ...
(Date:10/29/2015)... Minn. , Oct. 29, 2015   MedNet ... supports the entire spectrum of clinical research, is pleased ... Minnesota High Tech Association (MHTA) as one of only ... in the "Software – Small and Growing" category. The Tekne ... individuals who have shown superior technology innovation and leadership. ...
(Date:10/29/2015)... BOSTON , Oct. 29, 2015  Connected health ... phenomena driving the explosion of technology-enabled health and wellness, ... his new book, The Internet of Healthy ... apps, sensors or smartphones even existed, Dr. Kvedar, vice ... model of health care delivery, moving care from the ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... ... November 25, 2015 , ... A long-standing partnership ... Professionals (OPBAP) has been formalized with the signing of a Memorandum of Understanding. ... OPBAP leaders Capt. Karl Minter and Capt. Albert Glenn Tuesday, November 24, 2015, ...
(Date:11/25/2015)... November 25, 2015 The ... is a professional and in-depth study on the ...      (Logo: ) , ... industry including definitions, classifications, applications and industry chain ... the international markets including development trends, competitive landscape ...
(Date:11/24/2015)... Malaysia , Nov. 24, 2015  Asia-Pacific ... contract research organisation (CRO) market. The trend of ... in lower margins but higher volume share for ... capacity and scale, however, margins in the CRO ... Organisation (CRO) Market ( ), finds ...
(Date:11/24/2015)... Calif. , Nov. 24, 2015 Cepheid ... will be speaking at the following conference, and invited ... New York, NY      Tuesday, December 1, 2015 ... New York, NY      Tuesday, December 1, 2015 ... Jaffray Healthcare Conference, New York, NY ...
Breaking Biology Technology: