Research team seeks solution to superbugs

While bacteria are all around us, Illinois State University’s Science Laboratory Building is home to a particularly hazardous strain. Distinguished Professor Radheshyam K. Jayaswal is purposefully nurturing Staphylococcus aureus (S. aureus), which he and a team of colleagues and students within the Department of Biological Sciences are studying to unravel mysteries surrounding the superbug that can be fatal.

Staphylococcus (staph) is a common genus of bacteria that comprises some of the body’s natural faunal; however, not all forms of staph are tolerated by humans. Staphylococcus aureus is rapidly becoming immune to antibiotics. Specifically strains such as Methicillin-resistant Staphylococcus aureus (MRSA) and Vancomycin-resistant Staphylococcus aureus (VRSA) are difficult to treat.

The Center for Disease Control reports an estimated 94,360 invasive MRSA infections occurred in the United States in 2005 alone, with 18,650 deaths. The threat continues to grow through the misuse of prescribed drugs.

Jayaswal, who has obtained more than $2 million in external funding for his research, is an international expert who advocates restricting prescriptions. According to Jayaswal, “About 30 percent of prescriptions are unnecessary, but just to please the patient they are prescribed anyway. Sometimes doctors prescribe unnecessary medications because they want to avoid potential lawsuits. If they make a misdiagnosis and didn’t prescribe anything, they could be in trouble.”

Unnecessary antibiotics are consequently given for ailments that can typically be overcome by the body’s natural immune system, including minor viruses and the common cold. Bacteria exposed to the antibiotic may die, but exposure to an antibiotic over time may create a resistance in the next population of the bacterium.

The problem is compounded by the fact that S. aureus is easily spread on such common items as a sink knob or a towel. Exposure results in a range of infections, from simple skin abscesses to toxic shock syndrome, pneumonia, septic arthritis, endocarditis, and food poisoning.

Though S. aureus can live harmlessly on the surface of the skin, serious infections occur when it enters the blood stream. Infections are common in sterile environments, such as hospitals, even though medical staff strive to keep tools and rooms sterile and clean. The most miniscule amount of bacteria can result in an infection. The ease of which it can be transferred and the versatility of the bacteria make S. aureus the number one cause of hospital-acquired infections.

MRSA bacteria can infect skin, blood, bone, heart, and lungs. Because it is resistant to the antibiotic methicillin, MRSA infections require special antibiotics—if they are available. The same is true for VRSA, which is resistant to vancomycin and was identified in 1997. Jayaswal studied why this occurred and found that under pressure, the bacteria mutated several genes to become resistant to vancomycin.

“Since there was no parent strain from which it became resistant, we examined the difference between parent and resistant strains before comparing the VRSA obtained from a patient and our own parent strain,” Jayaswal said. Other studies were completed at the University of Chicago and Rockefeller Center in New York.

“We were all coming up with the same data and were getting published at the same time. Though we are a smaller school, we are getting the same regard that bigger schools are receiving, and got the same results. It makes you proud of your research and your school,” said Jayaswal, who came to Illinois State in 1988.

An undergraduate student of chemistry and physics at the University of Mumbai, Jayaswal joined the Tata Institute of Fundamental Research as a lab assistant. He completed a master’s in molecular biology from Bombay University and his doctorate at Purdue University.

“My interest has always been in science, but as I grew my interest changed from medicine to microbiology,” he said. During his post-doctoral work at Purdue, he began exploring the molecular biological aspects of plant-microbial interactions. “From there my interests kept growing in the mechanism in disease development,” said Jayaswal, who passed on the opportunity to work for several biotech companies and preferred to do research at ISU.

“When I came to Illinois State one of my collaborators, Brian Wilkinson, was working on the physiological/biochemistry aspect of staph,” Jayaswal said. “We started working on the various aspects of staph and have been focusing on the mechanism of how drug resistance develops in the bacteria.”

Jayaswal has developed a master’s sequence in biotechnology and a doctoral sequence in molecular and cellular biology while at Illinois State. He also obtained independent research funding through the National Institutes of Health, the American Heart Association, and the American Cancer Society. He has published 76 peer-reviewed articles in journals and has presented his research findings at conferences worldwide, becoming a respected voice on S. aureus internationally, particularly as the issue of antibiotic use becomes a global concern.

More than 70 percent of the antibiotics produced in the United States are given to animals to influence growth or protect against diseases. In this way, staph bacteria grows resistant through interacting with animals before finding its way to humans.

“When the bacteria are exposed to the antibiotics, they develop their resistance. If we don’t control the misuse of antibiotics, there will be a big problem,” Jayaswal said. He also warns that depending on pharmaceutical companies to produce new drugs is an unreliable strategy, as research on new antibiotics is rapidly being discontinued.

“It takes approximately one billion dollars to produce a new antibiotic. That includes research, testing, and FDA approval. It’s time consuming and can take 10 to 25 years before it gets to the pharmacy,” Jayaswal said. “When you spend so much time and money on a new antibiotic, and an antibiotic becomes resistant in two to three years, companies do not see the value for them.”

They instead focus on designer drugs, such as Lipitor and Viagra. These drugs can easily make back the substantial company investment and enjoy a much longer period on the market. The result is that the drugs methicillin and vancomycin, which are generally used to treat MRSA and VRSA infections, have few successors. Daptomycin can be used to treat both, but just as the bacteria eventually acquired a resistance to the first two drugs, it is only a matter of time before daptomycin becomes ineffective.

Despite studies showing the increasing resistance, little has been done at the government level to restrict the use of unnecessary medications. The Preservation of Antibiotics for Medical Treatment Act introduced in 2009 by New York Sen. Louise Slaughter calls for the Food and Drug Administration to review use of drugs on animals that are not sick. The bill has not been passed.

“Farmers lobby against the bill because they are concerned that if they do not continue the use of these antibiotics, the animals will die or not be as productive,” Jayaswal said. “Other lobbyists are from pharmaceutical companies themselves. They sell 70 percent to the farmers and don’t want to lose that money.”

On the state level California, Illinois, New Jersey, and Washington have passed bills that require hospitals to take measures to prevent the spread of MRSA by tracking, reporting, screening, and testing designated at-risk hospital inpatients for colonization and active infection.

“I think that every state should pass a similar bill that will restrict the spread of MRSA from the hospitals. As far as misuse is concerned, no state has done anything about that,” Jayaswal said. He noted that other countries such as Denmark and Norway have restricted antibiotic use in animals to situations where there is illness.

In the meantime Jayaswal continues to study various strains of staph to understand how they change to gain resistance. He welcomes students to his laboratory, supervising more than 50 undergraduates and serving as major professor to 23 graduate students. In an environment where even the slightest contact can cause infection, Jayaswal makes sure all of his students are protected.

“We minimize the risk to researchers by taking precautions. There is no eating or drinking. They have to wash their hands if they want to touch their nose and face. Any scratch or wound must be entirely covered,” Jayaswal said. “Whenever we do the experiments all strains are killed completely when we are done. Nothing is disposed of improperly. Everything is completely destroyed.”

With such strict precautions in place, Jayaswal’s lab has remained incident free in the quest to comprehend the minute molecules that can pose such an enormous threat. The work is daunting, but Jayaswal and his team are determined to win the fight.

“We have been using new technologies to look for similar problems in the future,” he said. “We always expect new problems, and continue working toward the future.”