DOHA—Doctors are finding it increasingly tough to treat infections due to a rising number of bacteria strains that are resistant to antibiotics. Nowhere is that truer than the Middle East, where it is still commonplace to buy the drugs over the counter without a prescription. That’s why a researcher at Qatar University has joined the hunt for new antibiotics that would kill bacteria in more innovative ways.
“Antibiotic resistance is a global plague,” says Susu Zughaier, an assistant professor of infectious diseases at Qatar University. “I’m trying to identify novel targets for antibiotics in bacteria that have acquired resistance.”
Additionally, Zughaier is trying to make antibiotics more specific, so they won’t deplete the patient’s friendly gut bacteria.
“We have a lot of bacteria that live within us that perform a lot of functions, such as helping us to digest our food, but when we take an antibiotic we also end up killing our friendly microbiota,” says Zughaier.
To avoid this, she is looking for proteins that are found only on the surface of bacteria that live outside the human body.
“It’s tedious but once you identify a potential protein expressed only in pathogenic bacteria, it gets going,” says Zughaier.
She uses 3D modeling software to visualize the structure of potential target proteins. This information allows her to predict which pre-existing drugs may be best suited to bind to a particular protein. She then conducts tests in the laboratory to see if this happens.
The next step is to identify the functions of these proteins. Ideally, they would be critical to the bacteria’s survival. Zughaier tests this by deleting the gene that codes for the protein. If the genetically modified bacteria cannot survive, then the protein is important and therefore a good candidate for antibiotic drugs to target.
Zughaier then double checks this in mice to verify that the genetically modified version of the bacteria can’t cause an infection.
The result of all these steps is to identify a new vulnerability in infectious bacteria, one that isn’t present in our gut bacteria, and to suggest a drug that could potentially exploit this weakness. The drug would then be optimized by pharmacologists to be properly viable.
Resistance to any new drugs created through Zughaier’s approach would be harder for bacteria to acquire because the drugs will be more specific and narrower in range, says Sima T. Tokajian, an associate professor of molecular microbiology at the Lebanese American University’s Byblos campus. Tokajian’s research in the past has tracked the geographical distribution of different strains of bacteria, with an aim to map the spread of resistance.
Zughaier has recently completed a study involving the bacterium that causes gonorrhea and is about to publish her results—she hopes a pharmacologist will then use her findings to create or modify a drug that will more effectively target the bacterium.
Research techniques like Zughaier’s differ from the conventional way of finding new antibiotics.
“The traditional method used to be to collect soil samples to look for microbes that produce antibacterial agents,” says Tokajian.
Tokajian says the scientific community needs to move away from the old way of finding new antibiotic drugs to counter the rise of resistance, but remains cautious in her optimism.
“It is too early to say if it will help the problem, but people need to be more innovative like this,” says Tokajian. “This is a really good start because it’s not sticking with traditional means. We’re reaching a point where that’s not good enough anymore.”
