October 2, 2017

VSU Develops Antibiotic that Effectively Treats Drug-Resistant Tuberculosis in Living Cells

VALDOSTA — Valdosta State University has developed an antibiotic that effectively treats some drug-resistant strains of tuberculosis (TB) in living cells.

The drug will soon progress to animal trials.

The results of this ongoing research were recently published by “Tuberculosis,” a specialty journal focusing on basic experimental research on TB.

This marks the first time that VSU’s ongoing TB drug research has been published in a medical journal. The paper is the fifth to be published on the VSU research but is the first one to examine how the TB drug works on living cells.

“This is still very much a research project, but we are excited to reach the point where the antibiotic is being tested on living things,” said Dr. Thomas Manning, a professor of chemistry who has been working on the TB drug with chemistry and biology students for roughly five years. “We are cautiously hopeful that our drug could eventually help heal people of a disease that ravages nations worldwide.”

TB is a deadly lung disease that remains a major problem in numerous third-world countries. One in three people have it, and one in seven people throughout history have died from it.

“The bacteria slowly dissolve your lungs,” Manning said. “You basically die of drowning in your own blood. It happens slowly. You’re coughing up blood. You lose a lot of weight. You just wither away, and then you can’t breathe anymore. It’s an agonizing death.”

The motivation behind the VSU research is to create a drug that can effectively treat TB at a low cost, especially in underdeveloped countries where the disease is widespread. In a country like South Africa, treatment for basic TB costs $15. However, the cost of treating a drug-resistant strain of TB is dramatically higher, often reaching into the six figures.

Instead of inventing a new antibiotic, VSU students have taken an existing antibiotic — isoniazid — and disguised it in a molecular structure that TB bacteria do not recognize, thereby making the antibiotic effective again.

The drug stops the TB bacteria from reproducing, and because the bacteria have a limited life span, the disease eventually dies out.

Tests of VSU’s drug were performed by the National Institute of Health (NIH) in Bethesda, Maryland. NIH is the top funder of TB research worldwide. Manning said that bringing a drug to the public market is a long, unpredictable process; it is never a guarantee that the drug will make it through testing and be commercialized. However, NIH has encouraged further testing of the drug, meaning it will now progress to animal trials.

Antibiotics that fight TB have been around since the 1960s, but TB bacteria build up resistance to antibiotics over time. As the bacteria grow smarter and stronger, the antibiotics become less and less effective.

“A molecule, or antibiotic, has a rigid structure,” Manning said. “The TB bacteria are always going to recognize that rigid structure and reject it. We hid our antibiotic inside a floppy structure that can sneak past the bacteria’s defenses. We basically repackaged the TB drug into a Trojan horse of sorts, and that worked.”

Manning said other research labs have experimented with repackaging antibiotics, but one of many fundamental differences in VSU’s drug is the inclusion of sucrose. The sugar speeds up the TB bacteria’s metabolism, causing the drug to be absorbed more quickly.

“Ours is completely different from any other drug out there,” Manning said.

The need for more powerful, more affordable TB treatment is what interested many VSU students in the research project.

“When the opportunity to work with the TB antibiotic was presented to me, I had no idea that TB is still a burden in the world,” said Tess Baker of Valdosta, Georgia, who graduated in Spring 2016 with a Bachelor of Science in biology and a Bachelor of Science in chemistry and is now a medical research associate at the University of Miami.

“It was and still is amazing to me that over one-third of the world's population still struggles with rising numbers of this disease, and foreign governments are still unable to get it under control.

“We learned of stories where children were ostracized from villages and left at the mercy of whoever may take pity on them because they had TB. In many countries, TB is still a death sentence. The more we researched this disease, the more we realized the positive impact our drug compilation could have.”

Kyle Wilkerson of Duluth, Georgia, said that the research has given him real-world experience and skills.

“I experienced being in a leadership role, learned how to use more types of equipment, expanded my overall knowledge of chemistry, and improved my confidence by demonstrating that the work I provided can potentially benefit the numerous lives impacted by TB,” said Wilkerson, who graduated in Spring 2017 with a Bachelor of Science in biology and is currently applying to medical schools.

Taylor Holder, who graduated from VSU in Spring 2017 with a Bachelor of Science in chemistry and is now in her second year of pharmacy school at the University of Illinois at Chicago, said the TB research prepared her for the next step of her career.

“Because I am going into pharmacy, being able to work on a project involving the efficacy of drugs is something that has let me broaden my understanding and knowledge,” said Holder of Chicago, Illinois. “Having a better understanding of antibiotics and resistance to drugs will greatly benefit me not only in my studies throughout pharmacy school but also in my profession.”

Andrew Carson Bartley of Chatsworth, Georgia, said the TB research proved to be challenging but enjoyable.

“I had to become familiar with technology and lab equipment that I have never used before in a short amount of time,” said Bartley, who graduated from VSU in Spring 2017 with a Bachelor of Science in biology. “I did multiple types of analyses that required an extensive amount of my extra time. I learned so much from the experience, and I am very glad that I did it.”

The VSU research team took its TB research to the National Science Foundation’s Innovation Corps program in Washington, D.C. The program teaches research groups what is required to achieve a commercial impact with their innovation.

Sydney Plummer, who graduated from VSU in December 2014 with a Bachelor of Science in biology, led the team. Kitty McLeod from the Bishop Foundation in Quitman provided weeks of business mentoring to the research team in preparation for the trip.

Once in Washington, Plummer, Baker, Manning, and McLeod met with ambassadors from several countries where TB is a heavy burden, and federal panels evaluated the TB drug for commercialization.

The TB research was also recently presented to 150 delegates from business, academia, government, and the non-profit sector at Ocean Exchange’s BIG Pitch Contest in Savannah, Georgia. VSU’s research group, led by Baker, was the only undergraduate team to make it to the finals.

Plummer and Baker both co-authored the patent application for the drug as well as several research papers on the antibiotic. Although they have graduated from VSU, they continue to participate in the ongoing research.

“Our research group under Dr. Manning was productive, fast-paced, and explorative,” said Plummer, who is now in her second year of doctoral studies at the Skidaway Institute of Oceanography, which is part of the University of Georgia.

“The vast majority of Dr. Manning’s students, myself included, did not have experience in writing patent applications or pitching business models prior to joining his group. That’s what is great about it. You are given challenging tasks that broaden your mind when thinking about science and its applications. It reminds you that your research has implications in real-world contexts, which can be forgotten by some scientists.”

Chelsea Jackson, who is expected to graduate from VSU in Fall 2017 with a Bachelor of Science in chemistry, said the TB research has helped her as a student but has also allowed her to address a pressing humanitarian need.

“Our work is an attempt to help the millions of people who suffer with TB worldwide,” said Jackson of Valdosta. “Along the way, I have picked up extensive scientific knowledge and learned how to do great research.”

“Tuberculosis” will print the VSU research article in its December 2017 issue. The paper, titled “Pharmacokinetic studies of a three-component complex that repurposes the front line antibiotic isoniazid against Mycobacterium tuberculosis,” is already available online at www.tuberculosisjournal.com.

The authors of the paper are Manning, Wilkerson, Plummer, Holder, Bartley, and Jackson; Dennis Phillips, director of the Proteomics and Mass Spectrometry Core Facility at the University of Georgia; Logan Krajewski, a graduate research assistant at the National High Magnetic Field Laboratory at Florida State University; and Greg Wylie, manager of the Nuclear Magnetic Resonance Facility at Texas A&M University.

Please contact Dr. Thomas Manning at (229) 333-7178 or tmanning@valdosta.edu to learn more.

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