Scientists Discover Hidden Weakness In Lyme Disease Bacterium

For decades, Lyme illness has disappointment some physicians and patients alike. Caused by nan corkscrew-shaped bacterium Borrelia burgdorferi, nan infection, if near untreated, tin linger for months, starring to fever, fatigue and achy inflammation.

In a caller study, Northwestern University and Uniformed Services University (USU) scientists person uncovered a astonishing - and ironic - vulnerability successful nan hardy bacterium. By exploiting this vulnerability, researchers could thief disarm B. burgdorferi, perchance starring to caller therapeutic strategies for Lyme disease.

The Northwestern and USU squad discovered that manganese, which helps shield B. burgdorferi against its host's immune system, is simultaneously besides a ace successful its armor. If B. burgdorferi is either starved of aliases overloaded pinch manganese, nan germs go highly susceptible to nan host's immune strategy aliases treatments they would different resist.

The study will beryllium published connected Thursday (Nov. 13) successful nan diary mBio.

"Our activity shows that manganese is simply a double-edged beard successful Lyme disease," said Northwestern's Brian Hoffman, who co-led nan study pinch USU's Michael Daly. "It's both Borrelia's armor and its weakness. If we tin target nan measurement it manages manganese, we could unfastened doors for wholly caller approaches for treating Lyme disease."

Hoffman is nan Charles E. and Emma H. Morrison Professor of Chemistry and molecular biosciences astatine Northwestern's Weinberg College of Arts and Sciences. He besides is simply a personnel of the Chemistry of Life Processes Institute and the Robert H. Lurie Comprehensive Cancer Center of Northwestern University. Daly is an emeritus professor of pathology astatine USU.

Since nan 1980s, nan occurrence of Lyme illness has accrued dramatically crossed North America and astir nan globe. According to nan Centers for Disease Control and Prevention, roughly 476,000 people in nan United States are diagnosed annually. Currently, location are nary approved vaccines against nan disease, and semipermanent usage of antibiotics is problematic. 

"Although antibiotics harm B. burgdorferi, they besides termination beneficial gut bacteria," Daly said. "Lyme illness is transmitted done tick bites and - if not treated promptly - tin origin lingering effects by attacking nan patient's immune, circulatory and cardinal tense systems."

In a bid of erstwhile studies, Hoffman and Daly collaborated to understand nan domiciled of manganese in Deinococcus radiodurans, a radiation-resistant bacteria known arsenic "Conan nan Bacterium" for its bonzer expertise to past harsh conditions. Now, they wanted to spot if manganese played a domiciled in B. burgdorferi'sdefenses.

To behaviour nan study, nan squad utilized a caller instrumentality called particle paramagnetic resonance (EPR) imaging to qualify nan atomic creation of manganese wrong nan surviving bacteria. To adhd moreover finer detail, nan squad harnessed particle atomic double resonance (ENDOR) spectroscopy to analyse nan atoms surrounding manganese. Together, nan technologies created a molecular map, showing which forms of manganese were present, wherever they were located and really they changed nether stress.

The "map" revealed a two-tier, manganese-based defense strategy comprising an enzyme called MnSOD and a excavation of manganese metabolites. To withstand bombardment from nan host's immune system, nan germs first usage MnSOD, which acts for illustration a shield. If immoderate oxygen radicals gaffe past this shield, they are met pinch nan metabolite pool, which acts for illustration a sponge to soak up and neutralize those toxic molecules.

Our study demonstrates nan powerfulness of EPR and ENDOR spectroscopies for uncovering hidden biochemical mechanisms successful pathogens. Without these tools, B. burgdorferi's defense strategy and anemic spots would person remained invisible."

Brian Hoffman, the Charles E. and Emma H. Morrison Professor of Chemistry and Molecular Biosciences, Northwestern's Weinberg College of Arts and Sciences

The scientists recovered nan germs perpetually juggle wherever to nonstop nan manganese - to nan MnSOD enzymes aliases nan metabolite pool. Too small manganese and nan germs suffer their defense mechanisms. But, arsenic nan microbes age, their metabolite pools dramatically shrink, leaving them exposed to harm and stress. At this point, excessively overmuch manganese becomes toxic because nan germs tin nary longer shop it safely.

This find holds imaginable for caller Lyme illness therapies. Future narcotics could starve nan bacterium of manganese, disrupt its expertise to shape protective manganese complexes aliases moreover push it into toxic overload. Any of these approaches would leave B. burgdorferi wide unfastened to onslaught by nan immune system.

"By disrupting nan delicate equilibrium of manganese in B. burgdorferi, it whitethorn beryllium imaginable to weaken nan pathogen during infection," Daly said. "Manganese is an Achilles' bottommost of its defenses."