New Tactics in the War on Superbugs

August 5, 2015

Between October and January, patients at Ronald Reagan UCLA Medical Center contracted a life-threatening superbug. Out of the nearly 200 patients who may have been exposed, seven were confirmed infected, and two died. Patients came into contact with the dangerous bacteria when a particular model of duodenoscope was used to check their gastrointestinal system. It is likely that these instruments underwent the usual cleaning and decontamination processes, and yet the superbugs were able to survive and spread. Once these bacteria find their way into the patients, even the most powerful antibiotics can do little to remove them. We have relied on antibiotics to eliminate bacterial infections for more than 70 years, so where do we turn when they stop working? Professor Dacheng Ren believes the key is to stop the superbug from ever having a chance to take hold in the body. One such strategy is to engineer better materials to reduce contamination. By studying the effects of material properties, including surface chemistry, stiffness, and topography, on bacterial adhesion and biofilm formation, better methods may be developed to defeat superbugs that stick to medical tools and other surfaces in health care settings. When bacteria—either pathogenic or friendly—stick together, they form a slimy layer called a biofilm that adheres to surfaces inside or outside the body. A good example is inside your mouth, which is coated with a biofilm that you can feel. We need to keep the bad bacteria off the surfaces where they cause harm. To do this, it’s important that we understand why certain biofilms tend to prefer some surfaces more than others. Ren’s lab explores how the stiffness and surface topography of polymers can affect bacterial adhesion, and the growth, morphology and antibiotic susceptibility of attached cells. Ren discovered that E. coli and Pseudomonas aeruginosa are less likely to stick to a stiff polymer surface than they are to a soft one, and the stiffness has a profound influence on the physiology of attached cells. Ren said, “We know that people are more comfortable sleeping on a soft, yet relatively firm surface—not something as hard as a concrete floor or as soft as a gel. The question we set out to answer was, ‘How much do bacteria care about the stiffness of the surface they rest on?’ We were surprised by just how much they cared. Our results revealed that surface stiffness is an important material property that influences the attachment, growth, morphology, and stress tolerance of biofilm cells.” The role of surface properties is just part of Ren’s research. Another promising method of controlling superbugs may involve interrupting a process called horizontal gene transfer. Here, bacterial cells living in biofilms can spread their ability to survive sterilization and resist antibiotics to other bacteria they come in contact with. When they live in biofilms, there’s obviously a greater chance for this to occur. Through a new grant from the Alfred P. Sloan Foundation, Huan Gu, a postdoctoral researcher in Ren’s lab, is conducting research to explore how surfaces in hospitals, ranging from tabletops to the tools like duodenoscopes, can be better designed so that biofilms cannot persist and continue to spread extremely harmful bacteria. “Our goal is to interrupt the horizontal gene transfer by controlling the topography of surface materials. By creating nano microstructures with specific patterns, we can reduce the frequency of DNA transfer between biofilm cells,” said Gu. Through this work, Ren’s lab continues to uncover new evidence about the effect a surface can have on cells in sticky biofilms, supporting his mission to understand and control these biofilms in the fields of disease control. Eventually, this knowledge may be used for a variety of applications that will help us avoid harmful infections and keep us healthy. Ren said, “Interrupting the process of horizontal gene transfer and killing the superbug before it can infect us is the key. We’re losing the battle when it comes to using antibiotics. We need to find alternative approaches to tackling this problem, and this research is part of such effort.”