Spotlight on a Researcher – Robert Smith, Ph.D.

Robert Smith, Ph.D. is a research scientist and an Associate Professor at NSU’s Dr. Kiran C. Patel College of Allopathic Medicine. Dr. Smith also serves as the Chair of the Faculty Research Advisory Council and is a member of the Provost Research and Scholarship Award Committee. He received his B.Sc. in Biology and Biotechnology and his Ph.D. in Biology from Carleton University in Ontario, Canada. Following his Ph.D., Dr. Smith pursued a postdoctoral research associate position at the Department of Biomedical Engineering in Duke University where was named a Duke Scholar in Infectious Disease. Currently at NSU’s Dr. Kiran C Patel College of Allopathic Medicine, his lab is focused on understanding how bacteria work together to regulate bacterial pathogenesis and antibiotic resistance.

The increased frequency of infections due to antibiotic resistant bacteria is considered as a major public health concern which, if not tackled adequately, will result in major clinical and financial challenges for both patients and the healthcare system. Despite the significant threat posed by antibiotic resistance, the mechanisms by which bacteria resist antibiotics as a population are poorly understood. One such mechanism is the inoculum effect. IE is defined as the loss of antibiotic efficacy with increasing density of a bacterial population. While IE has been described for nearly all antibiotics, a mechanism to explain IE for antibiotics from different classes has yet to be identified. To address this knowledge gap, and using a combination of flux balance analysis, mathematical modeling and experimentation, Dr. Smith’s team discovered that interactions between bacterial growth rate and bacterial metabolism determine IE. By manipulating the relationship between these two facets of bacterial physiology, they could eliminate IE for multiple antibiotics. Their findings were published in Science Advances (https://www.science.org/doi/full/10.1126/sciadv.add0924?_aiid=12167). This research may lead to the discovery of novel bacterial targets, or therapeutics, to reduce IE in the clinical setting.

While bacteria can resist antibiotics as a population, they can also exchange pieces of DNA that confer antibiotic resistance through a process called bacterial conjugation. While bacterial conjugation has been observed to affect growth of bacteria, little is known how conjugation altered bacterial metabolism. Working along with Dr. Allison Lopatkin at the University of Rochester, it was recently discovered that genes involved in regulating bacterial metabolism are prevalent on plasmids that are passed between bacteria during conjugation. In recent manuscript published in ISME J, (https://www.nature.com/articles/s41396-022-01329-1 ), this collaborative team found that genes involved in metabolism and that are found on conjugative plasmids can increase antibiotic resistance against multiple antibiotics from different antibiotics classes. This work lays the groundwork to understand how metabolism is perturbed by conjugation, and how genes found on conjugative plasmids, that are not specifically targeted for antibiotic resistance, can alter antibiotic susceptibility.

Virulence factors play important roles in bacterial pathogenesis. One such virulence factor is pyoverdine, which allows populations of bacteria sequester iron from their host. Previous work has shown that reducing the amount of pyoverdine produced by bacteria can reduce infection severity.  Dr. Smith and his collaborators have recently discovered that periodic application of a physical force to a population of Pseudomonas aeruginosa can alter the production of pyoverdine. As shown in their manuscript published in mSystems (https://journals.asm.org/doi/full/10.1128/mSystems.00961-21 ), the showed that interactions between the amount of pyoverdine produced by strains isolated from the clinic, and biofilm formation, determines the impact of periodic disturbance.  In some instances, periodic disturbance could significantly reduce the amount of pyoverdine.  Building on this, the applied the same physical force to populations of Staphylococcus aureus. They found that these physical forces could reduce the expression of multiple virulence factors in S. aureus. This work, published in Applied and Environmental Microbiology (https://journals.asm.org/doi/10.1128/aem.01932-22 ), lays the groundwork for using physical force to reduce infection severity in the clinic.

The research conducted in Dr. Smith’s lab at NSU’s College of Allopathic Medicine will help the scientific community gain a better understanding of mechanisms through which populations of bacteria resist antibiotics. These findings will have implications in understanding evolution of bacterial antibiotic resistance, preventing infections and may lead to creating novel antibacterial treatment(s).