UNR researchers’ medical findings show promise against deadly bacterial diseases

In the battle against deadly diseases that adapt quickly to resist today’s top antibiotics, researchers from the University of Nevada, Reno have shown that stopping bacterial cells from communicating can actually prevent them from amassing their lethal armies.

Following more than five years of research, University chemical biologist Yftah Tal-Gan and his team successfully demonstrated that interrupting the deadly Streptococcus pneumoniae bacteria’s communicative mechanism could lead to significant advances in medicine, eventually saving countless lives.

The team studied “quorum-sensing” bacteria that synchronize the activities of large groups of cells by communicating via chemical signal molecules. The potentially game-changing research has just been published in the prestigious Proceedings of the National Academy of Sciences.

Employing robotic, automated batch sampling and other testing on slightly modified configurations of peptides (chains of amino acids), the team recently synthesized a peptide shown effective on the two deadly strains of Streptococcus pneumoniae. The synthetic peptide developed by Tal-Gan’s team effectively cuts off the bacteria’s communication. In doing so, the synthetic peptide not only stops the bacteria’s potentially lethal attacks on the body; it also halts what is known as “selection pressure” – the process akin to natural selection through which the strongest bacteria survive to become drug-resistant.

Streptococcus pneumoniae attacks compromised or undeveloped immune systems, making the elderly and children especially vulnerable. It is blamed for over 22,000 deaths, 400,000 hospitalizations and $3.5 billion in health care costs annually in the United States alone – and an estimated 800,000 deaths globally among children age 5 and under.

Overcoming the challenge of drug resistance

“People don’t realize it, but bacteria are smart – they communicate, they adapt,” Tal-Gan said. “The big issue today is that Strep pneumoniae builds up resistance to drugs, making them stronger and rendering the antimicrobials ineffective. Through our research, we have synthesized peptides in a way that interrupts the bacteria’s communication, keeping them from rallying their harmful forces and from initiating resistance to drug therapies.”

Not only do bacteria communicate, they use the buddy system. “It makes sense that if you get a scratch, you’ll have a few bacteria in your bloodstream,” Tal-Gan explained. “Your strong immune system is going to kill them in a second. So instead, the bacteria are going to hide and build their army. It’s only when they reach critical mass (a “quorum”), when they know they have the numbers, that they begin synchronizing all together to start producing virulence (disease-producing) factors to overwhelm the immune system and establish an infection.”

By exploiting this mechanism, Tal-Gan’s team has demonstrated that it is possible to moderate or eliminate the bacteria’s disease-producing capability without killing them, preventing the unintended-but-certain resistances the world is grappling with today.

The findings are now being published within the international scientific community and the team has begun exploring avenues for deploying their new synthesized peptides as a therapeutic strategy, as a standalone or in combination with antibiotics or vaccines. The team has filed for a patent and is seeking funding and partners to optimize the molecules further and develop treatment strategies, including new pharmaceuticals to improve the desired therapeutic effects. That research is in its early stages, yet the science behind it is now proven to have merit. The next phase of research could elevate Tal-Gan’s team’s breakthrough to even higher levels.

“Like so much of what we do in the College of Science at the University of Nevada, Reno, the research of professor Tal-Gan and his entire team is high-value, high-impact science,” Jeff Thompson, the College’s dean, said. “Breakthrough discoveries like this don’t just happen. It takes resources, vision and a collaboration of smart people persisting daily to solve the world’s most critical challenges.”

Research team, funding

The research team was comprised of principal investigators Tal-Gan of the University of Nevada, Reno and Gee W. Lau, Tal-Gan’s collaborator from University of Illinois at Urbana-Champaign; Yifang Yang and Anthony Harrington, University of Nevada, Reno graduate students; Gabriel Cornilescu, staff scientist at National Magnetic Resonance Facility at Madison, Wisc., and Jingjun Lin, graduate student at UIUC.

A peptide chemist by training, Tal-Gan’s early interest in biology and chemistry eventually led to his ultimate passion. “I fell in love with bacterial communication, and that was it. I never looked back,” Tal-Gan said. “It’s just fascinating, so cool.” Tal-Gan joined the University’s College of Science in 2014, where he currently serves as an assistant professor.

The first five years of research by Tal-Gan’s team was funded by a bridge INBRE grant (IDeA Networks of Biomedical Research Excellence) from the National Institute of General Medical Science and a $1.8 million NIH R35 grant to the Tal-Gan lab. Last April, Tal-Gan and Lau jointly secured a $2 million National Institutes of Health (NIH) grant (National Heart, Lung and Blood Institute R01 grant) to provide up to four years to further develop and test the synthesized peptides.