COVID-19 has brought home the pressing need to develop novel treatments for infectious diseases. It’s a battle we are waging on many fronts. One important struggle opposes the so-called superbugs, microorganisms that have strengthened themselves over time against traditionally effective antibiotic therapies. Our research group at Purdue is devising a counterattack — using pulsed electric fields alongside conventional antibiotics to better kill the germs.
Ever since the discovery and further advancement of antibiotics, microorganisms have been developing resistance to the treatments. This, in turn, has led to increasingly stronger antibiotics, and antibiotics that target different pathways to get at the pathogen. The microorganisms then develop immunity to these treatments — in what essentially is escalating biological warfare.
One major thrust of my research group is the application of intense electromagnetic radiation to manipulate biological cells. We are working on combining this technology with antibiotics to inactivate (kill) antibiotic-resistant microorganisms. By bringing together novel electric pulse waveforms (to be delivered via needle arrays, creating nanometer-sized membrane pores in the microorganisms that cannot reseal) with various antibiotics, we can enhance the antibiotics’ effectiveness and dramatically improve their speed of action with dosages below clinical levels.
We have also demonstrated that we can use electric pulses to make antibiotics effective against microorganisms for which they are not designed — paving the way to repurpose existing FDA-approved drugs, rather than going through a long and expensive antibiotic development cycle.
My PhD student and I are collaborating with a small company that works out of Purdue University’s Birck Nanotechnology Center, Nanovis LLC, to apply electric pulses (EPs) to inactivate microorganisms. We have discovered a novel synergy: Combining these electric pulses at levels insufficient to kill the microorganisms with drug levels that also are inadequate can in fact kill the microorganisms, and act much faster.
For example, adding even 1/20 of the clinical dose of the antibiotic tobramycin to a train of EPs induced between 2.5 and 3.5 log inactivation after only 10 minutes of exposure — compared with taking hours to induce inactivation using a clinical dose with no EPs (log is a factor of 10, so 2-log is 100 times reduction, 3-log is 1,000 times reduction, etc.). Similarly, combining a series of EPs with a clinically relevant dose of rifampicin, another common antibiotic for treating bacterial infections, induced 7–9 log inactivation over the same time of exposure.
This approach is crucial in treating infections caused by “Gram-negative” microorganisms, such as C. difficile. Gram-negative bacteria (so named because they are identified by a staining technique developed by the Danish bacteriologist Hans Christian Gram in 1884) have a thin cell wall with an outer and inner membrane. The “camouflaged” outer membrane hides the bacterial microorganism’s antigens, tricking the body into limiting its immune response.
We have shown that Gram-positive antibiotics, which do not work against Gram-negative bacteria because they cannot pass through their double membranes, can be made effective by combining them with the pulsed electric fields. Novel treatments like these are important because Gram-negative bacteria cause serious infections like pneumonia, and can infect the bloodstream, wounds, and surgical sites. Their resistance to multiple drugs, and to most of our currently available antibiotics, make them potentially deadly.
We are working with industrial partners on additional uses for EPs. For instance, we are exploring the stimulation of muscle and bone stem cells, using electric pulses to speed up cell proliferation for faster bone formation in vitro. We are collaborating with other researchers using electric pulses to activate platelets, causing the release of growth factors to accelerate wound healing. Another application involves extending the shelf life of food, and our research group is exploring uses in agriculture, bioenergy, cancer treatment, and nondestructive testing, among other areas.
Electric pulses may also be of use in fighting COVID-19. Researchers are investigating the possibility of decontaminating areas exposed to the airborne novel coronavirus using microwaves to reduce its infectiousness. This could be of tremendous benefit to medical personnel working in hazardous settings.
Allen L. Garner
Associate Professor and Undergraduate Program Chair, School of Nuclear Engineering
Associate Professor (by courtesy), School of Electrical and Computer Engineering
Associate Professor (by courtesy), Department of Agricultural and Biological Engineering
College of Engineering, Purdue University