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Benjamin Luft

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Pixabay photo

By Daniel Dunaief

Benjamin Luft. Photo courtesy of SBU

They bother us, particularly in the summer, but they don’t need us.

The 23 species of Borrelia bacteria, which cause Lyme disease, have been around for millions of years, dating back to when the continents were all linked together like pieces of a puzzle in Pangea. The bacteria likely infected early mammals in those days.

In a recent paper in the journal mBIO, researchers from over 12 institutions put together the genetic sequence of these bacteria, which include 47 strains.

The scope of the work “was enormous and we were lucky” to have so many dedicated investigators, said Ben Luft, Edmund D. Pellegrino Professor of Medicine at the Renaissance School of Medicine at Stony Brook University, including lead senior author Weigang Qiu, Professor of Biology at Hunter College of the City University of New York.

The work, which took about a decade to complete, could provide a valuable resource to researchers and doctors today and in the future. The genetic information could lead to advances in diagnostics, treatment and prevention of Lyme disease.

Scientist could use the database to compare the genomes of different species and variations that cause different symptoms to help diagnose the likely severity of an infection as well as to search for specific pathways that lead to the virulence of an infection.

Some infections can lead to fever, headaches, fatigue and a skin rash. Starting with the bite of an intermediate host such as a tick, these infections, when left untreated, can lead to problems in the joints, heart, and nervous system.

The number of new cases of Lyme disease each year has been climbing, reaching close to 500,000 per year in the United States.

Researchers added that creating a genetic catalog of the different bacterial species can also help current and future scientists and doctors manage new threats from strains of bacteria that move into new areas amid climate change.

These species haven’t interacted with each other in the past, but climate change may create opportunities for bacteria to create recombinant genes, presenting new threats to human health.

“You may start seeing things that you didn’t see before,” said Luft. “We don’t know what’s going to happen” amid climate change. “There might be new forms” of Lyme disease.

The challenge with Lyme is not necessarily what happens in 2024, but how it might change in 20 years, when organisms develop a new pathogenicity.

Lyme on four continents

An international team of researchers sequenced the genomes of many species of Borrelia, the cause of Lyme disease. By comparing these genomes, the researchers reconstructed the evolutionary history of Lyme disease bacteria. The map shows many of the global regions where the team sequenced a species. Borrelia burgdorferi, the most common cause of disease, is indicated in red. Other species are indicated by different colors. Image created by Saymon Akther

In addition to generating a database of the Lyme disease bacterial genome, the researchers wanted to develop an understanding of its phylogenetic history.

“The goal really was to show how genetically diverse Borelia is throughout the world,” said Luft.

The researchers gathered genetic data from this bacteria, which was sampled in Europe, Asia, and North and South America.

By collecting the genetic information in each of these locations, the scientists were able to recreate the history of a bacteria that’s lasted considerably longer than many other organisms that have since become extinct.

“The genetic make up (genes and plasmids) hasn’t changed very much since the last common ancestor on Pangea (otherwise we would see different sets of genes and plasmids from different continents),” explained Qiu.

An extensive collaboration

Qiu and Luft were grateful for all the work scientists around the world did to contribute to this study.

On Long Island, Lyme disease is transmitted mainly by the bite of an infected deer tick, also is known as the black-legged tick.

The team of Claire Fraser and Emmanuel Mongodin at the University of Maryland School of Medicine and Richard G. Morgan of New England Biolabs helped use next generation sequencing to determine the bacterial genome.

Indeed, Fraser was the first to map the complete genetic code of a free-living organisms. She worked with the Haemophilus influenza, which causes respiratory infections and meningitis in infants and young children, according to the University of Maryland School of Medicine.

Qiu, who earned his Phd from Stony Brook in 1999, suggested that the effort required regular, ongoing work. He supervised Dr. Saymon Akther for her thesis work, which was the basis of the paper. He also performed additional evolutionary analysis.

“For the past two years, we have been having weekly meetings on zoom,” said Qiu. “It’s a big relief” that the researchers published the study and shared the information with the scientific community.

Qiu credited Luft with being a consistent coordinator of the sequencing effort and diversity study for over 20 years.

The next steps

At this point, Luft and his colleagues are eager to share the information with the broader scientific community.

The researchers hope experts in artificial intelligence, bioinformatics and computer programming can use the data to understand more about the genome and develop potential therapeutic targets.

Luft is eager to see “how smart people take advantage of a decade’s worth of work that has been very carefully done, to move it all forward,” he said. “We have certain ideas that we are doing” to fill in the gaps.

Qiu has some existing grants he’s using to work on diagnostics and vaccine development.

Qiu, along with chemistry-department colleague Brian Zeglis, and Lyme diagnostic/ vaccine researcher Maria Gomes-Solecki, has a joint NIH/ NIAID grant to develop a novel PET-based technology to detect Lyme pathogens in vivo. They have also proposed a new Lyme vaccine design strategy.

Additional sequencing of the variable plasmid, which is not a part of the chromosomal DNA but can replicate independently, would continue to help determine what genetic codes contribute to the level of virulence for each strain or species.

“That’s like the last mile for the communication network,” said Qiu. The challenges include annotating the genomes, providing comparative analysis and using informatics development to share the genome variability with the research community.

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Sean Clouston

By Daniel Dunaief

Every year, the country pauses on 9/11, remembering the victims of the terrorist attacks and reflecting on the safety and security of the country. At the same time, a Stony Brook University study continues not only to remember the first responders but also to understand the physical and mental consequences of the work police, firefighters and other first responders performed in the immediate aftermath of the attacks.

Benjamin Luft

Recently, Sean Clouston, an associate professor in the Department of Family, Population & Preventive Medicine at SBU Renaissance School of Medicine, and Ben Luft, the director of the SBU WTC Health and Wellness Program since 2003, published research in which they demonstrated a link between a protein commonly connected with Alzheimer’s disease to post-traumatic stress disorder, or PTSD, in first responders.

In a small preliminary study, the researchers found a difference in the level of the protein between first responders who are battling chronic PTSD and those who aren’t battling the condition. The Stony Brook scientists published their work in the journal Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring.

The researchers cautioned that the presence of the markers doesn’t necessarily indicate anything about present or future changes in cognitive function.“We don’t know the specificity of the markers,” Luft explained in an email.

Amyloid is generally considered the earliest marker of Alzheimer’s disease, which includes cognitive decline. Some people, however, have significant amounts of amyloid and don’t develop problems with their thinking. Neurodegenerative diseases without amyloid rarely have severe symptoms, which don’t appear to worsen with time.

“This paper doesn’t look at cognitive symptoms,” Clouston said. “We do have papers looking at cognitive impairment and other memory-based differences. It wasn’t a part of this paper.”

The newest research is part of an ongoing program in which the university follows 11,000 responders who came to the World Trade Center. The study for this paper involved a smaller subset of this population. This type of research can and does have application to other studies of people who have traumatic experiences, the scientists suggest.

Most traumatic experiences are unique to each person, as people who suffer physical and emotional trauma in combat often confront the aftereffects of head injuries. Among the first responder population who survived the attacks on 9/11, most of them “faired pretty well physically,” Clouston said. 

“We didn’t have a lot of head injuries. Understanding PTSD in this crowd is really useful for the literature as a whole because it allows us to focus on the long-term psychiatric fallout of an event without worrying about exposures that are different.”

The scientists had at least some idea of the timing and duration of exposures. This research suggests that it might be helpful to think about the kinds of problems that cognitive impairment can cause, which might involve managing other health-related problems.

Luft added that the population they are studying shows the benefit of immediate care. “One thing for sure is that the care of the first responders has to occur very quickly,” he said. “Now that we know the history, the greatest chance you have in mitigating the effect of this type of trauma is to deal with the problem from the get-go.” 

Sean Clouston with his daughter Quinn at Benner’s Farm in Setaukt. with his daughter Quinn. Photo by Rachel Kidman

First responders have benefited from psychotherapy as well as from various pharmacological treatments. Luft suggested that they might even benefit from having therapists available in the field, where they can receive near instantaneous psychological support.

In addition to the psychological trauma, first responders have had physical effects from their work in the aftermath of the attacks, such as respiratory and gastrointestinal problems, as well as autoimmunity issues.

People have these problems because “of the pro-inflammatory effect of PTSD itself,” said Luft. The researchers believe trauma can affect the immune system and the brain.

According to Clouston, the next step with this work is to replicate it with a larger scale. The experiment was “fairly expensive and untried in this population and novel in general, so we started small,” he explained in an email. The scientists would like to “get a larger range of responders and to examine issues surrounding symptomatology and other possible explanations.”

Clouston has been at Stony Brook for six years. Prior to his arrival on Long Island, he worked on a collaborative project that was shared between University College London and the University of Victoria. 

An expert in aging, he felt like his arrival came at just the right time for the WTC study, as many of the first responders were turning 50. After giving talks about the cognitive and physical effects of aging, he met Luft and the two decided to collaborate within six months of his arrival.

Clouston is focused on whether PTSD caused by the terrorist attacks themselves have caused early brain aging. A self-proclaimed genetics neophyte, he appreciates the opportunity to work with other researchers who have considerably more experience in searching for molecular signatures of trauma.

Clouston said his family has suffered through the trauma of cognitive decline during the aging process. His family’s struggles “definitely bring [the research] home,” reminding him of the “terror that many family members feel when they start noticing problems in their siblings, parents, spouses, etc.”

As for his work on the recent study, he said he is excited about the next steps. “Little is known about the subtypes of amyloid,” he suggested and there’s a “lot more to explore about the role [of this specific type] in the population. I do think it could be really informative about the types of symptoms.”

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